Crohn's Disease
Vorinostat and Ustekinumab for Moderate-to-Severe Colitis
This study examines the safety and effects of vorinostat in adults with treatment-resistant moderate-to-severe colitis, followed by extended vorinostat and possible ustekinumab maintenance for participants who respond.
Registry title: An Open-Label, Proof of Consent Study of Vorinostat for the Treatment of Mdoerate-to-Severe Crohn s Disease and Maintenance Therapy With Ustekinumab
1 recruiting U.S. site ↓Study at a glance
- Age
- 18 Years–65 Years
- Treatment
- Vorinostat or Ustekinumab
- Design
- Non Randomized
- Central study contact
- Ivan J Fuss, M.D.(301) 761-7091ifuss@niaid.nih.gov
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
Research question
Can vorinostat be given safely and tolerably to people with moderate-to-severe colitis, and can ustekinumab be used safely as maintenance after a response to vorinostat?
Participant snapshot
Who the study is looking for
- The study is looking for adults ages 18 through 65.
- The study is looking for people with endoscopically or radiographically confirmed Crohn’s disease, ulcerative colitis, or chronic granulomatous disease colitis.
- The study is looking for people with active moderate-to-severe symptoms, such as continued weight loss, abdominal pain, or diarrhea not controlled by standard therapy.
- For Crohn’s disease or ulcerative colitis, the study is looking for people whose disease did not respond adequately, stopped responding, or was intolerant to at least one specified treatment group.
- The listed recruiting location is the National Institutes of Health Clinical Center in Bethesda, Maryland.
Participation overview
What participation may involve
Participation begins with screening, followed by 12 weeks of oral vorinostat. Participants who respond and can safely continue may receive extended vorinostat and then up to two years of ustekinumab maintenance. What participation may involve: - Screening may last up to 120 days and includes a physical examination, medical history, questionnaires, symptom diary, and blood, urine, stool, heart, and tuberculosis testing. - During initial treatment, participants take vorinostat by mouth twice daily for 12 weeks, receive weekly calls, have blood collected regularly, and attend checkups every four weeks. - Responders who safely continue vorinostat may enter an additional six-month extension with weekly calls, regular blood collection, and checkups every three months. - Participants entering ustekinumab maintenance receive one intravenous loading dose, then 90 mg under the skin every eight weeks for two years, with NIH evaluations and follow-up calls. Reported phases include screening for up to 120 days, 12 to 13 weeks of initial treatment, an additional six months of vorinostat for eligible responders, and two years of ustekinumab maintenance for participants who proceed to that phase. The record describes checkups every four weeks during initial vorinostat treatment, then every three months during its extension. Ustekinumab visits occur every eight weeks at the NIH Clinical Center, with calls three days and two weeks after each dose.
Study interventions
What participants may receive or do
- Vorinostat: Participants receive oral vorinostat 100 mg twice daily for 12 weeks. Those who respond and can safely continue may receive an additional six months. The registry states that its use for this study is off-label.
- Ustekinumab: Participants who achieve a defined response or remission with vorinostat may receive a weight-based intravenous loading dose, followed by 90 mg under the skin every eight weeks for two years.
Study design
How the comparison works
This is an open-label, non-randomized interventional study. Everyone entering treatment receives vorinostat; later treatment depends on response and safety, and qualifying responders may proceed to ustekinumab maintenance. The registry states that assignment is non-randomized and uses a single-group intervention model. The study has no masking, so participants and study staff know which treatment is being given. The registry labels the ustekinumab arm as an active comparator, but the descriptions present it as later maintenance for participants who respond to vorinostat rather than as a parallel comparison group. No placebo or sham intervention is listed.
Reported activities
Procedures and tests
- Physical examination and medical-history review during screening.
- Blood, urine, and stool testing, with regular blood collection during treatment.
- A heart test during screening; the eligibility criteria specifically discuss a baseline electrocardiogram.
- Tuberculosis testing during screening.
- Questionnaires and a diary recording symptoms.
- A baseline colonoscopy is required to document mucosal disease activity, and research biopsies must be accessible by standard colonoscopy.
- The record says lymphapheresis collection may be offered under a separate consent.
- Clinical disease-activity scores are assessed, including the Crohn’s Disease Activity Index, Mayo score, or Harvey-Bradshaw Index depending on the condition.
- Endoscopic scores, tissue findings, symptom scores, and immunologic and laboratory measures are used to assess response.
- An end-of-study visit after ustekinumab includes repeated screening tests and a colonoscopy.
Eligibility highlights
Details that may affect whether you contact the study
These are selected highlights, not a complete eligibility check. Exact criteria remain in the full registry record below.
Common requirements
- Participants must be 18 through 65 years old at enrollment.
- Crohn’s disease, ulcerative colitis, or chronic granulomatous disease colitis must be confirmed by endoscopy or imaging.
- A baseline colonoscopy must document active mucosal disease and meet the condition-specific minimum endoscopic score.
- Participants must meet the stated condition-specific activity score and have continued weight loss, abdominal pain, or diarrhea not controlled by standard therapy.
- For Crohn’s disease or ulcerative colitis, at least one specified treatment group must have produced an inadequate response, loss of response, or intolerance; symptomatic chronic granulomatous disease colitis is evaluated individually.
- Permitted bowel-disease medicines must meet detailed stable-dose or discontinuation windows before baseline.
- Specified biologic, JAK-inhibitor, and systemic immunosuppressive treatments require washout periods ranging from eight weeks to three months before baseline.
- Participants must have a primary medical care provider.
- The study has detailed pregnancy-prevention requirements for participants who could become pregnant and for male participants with partners who could become pregnant.
Possible reasons someone may not be able to join
- A clinically significant systemic infection within three months of screening is exclusionary.
- Recurrent or chronic viral, bacterial, systemic fungal, or syphilis infection is exclusionary.
- A positive tuberculosis test, active tuberculosis history, or chest imaging suggestive of old tuberculosis is exclusionary.
- Blood counts, kidney tests, liver tests, clotting results, and bilirubin must remain within the protocol’s specified limits.
- A stool test positive for gastrointestinal pathogens that may cause infectious diarrhea is exclusionary.
- Bowel surgery other than specified perianal procedures within six months before screening assessments is exclusionary.
- Gut anatomy that prevents use of the required disease-activity measures, including an ileostomy, colostomy, or subtotal colectomy with ileorectal anastomosis, is exclusionary.
- Disease limited to areas inaccessible for research biopsies by standard colonoscopy is exclusionary, including only upper gastrointestinal or only perianal fistulizing disease.
- Participants must be willing to avoid cyclooxygenase-2 inhibitors and nonsteroidal anti-inflammatory drugs throughout study-drug administration.
- Participation in another investigational trial within eight weeks or five drug half-lives, whichever is longer, before screening is exclusionary.
Important unknowns
What the record does not make clear
- The criteria provide detailed rules for several existing medicines, but the record does not give a simple, complete account of which treatments continue, taper, or stop in every study phase.
- The record does not describe what rescue treatment is available if colitis worsens during study treatment.
- The summary says participants may have a screening colonoscopy, while the eligibility criteria require a baseline colonoscopy; an end-of-study colonoscopy is also described for the ustekinumab phase.
- The record does not explain which study-related or routine-care costs are covered or billed to insurance.
- The record does not state whether participants receive compensation.
- The record does not state whether transportation, lodging, meals, or other travel expenses are supported.
- Telephone follow-up is described, but the record does not say whether any required evaluations may be completed locally or remotely.
- The record does not describe access to vorinostat or ustekinumab after study participation ends.
- The registry condition list names only Crohn’s disease, while the official title, detailed description, and eligibility criteria also describe ulcerative colitis and chronic granulomatous disease colitis.
Before contacting the site
Questions for the study team
- Which diagnosis groups are currently enrolling, and is the Bethesda cohort open for my diagnosis?
- Which current medicines must remain stable, be tapered, or complete a washout before baseline and during treatment?
- Exactly which colonoscopies and biopsies are required in each phase I might enter?
- What happens if my disease worsens or I cannot tolerate vorinostat or ustekinumab?
- What response and safety findings are required to enter the extended-vorinostat and ustekinumab phases?
- Which visits must occur in Bethesda, and can any blood tests, evaluations, or follow-up calls be handled locally?
- Which study-related expenses are covered, and are compensation, transportation, or lodging support available?
- What care and medication access are planned after my study participation ends?
Before changing care
Questions for your gastroenterologist
- How could the protocol’s medication stability and washout rules affect control of my disease?
- What approved treatment alternatives remain reasonable for me before I consider research participation?
- Is my disease stable enough to undergo the screening period and the protocol’s required medication changes and procedures?
- What risks of vorinostat or ustekinumab are most important in the context of my infections, laboratory results, other conditions, and current medicines?
- How should my gastroenterology team and the NIH research team coordinate monitoring and treatment if my symptoms worsen?
This plain-language digest is provided by the Aidy clinical trials API. It may omit details and is not medical advice or an eligibility decision. Review the full registry record and confirm details with the study team.
Source record
Full registry record
The sections below preserve the study information supplied through ClinicalTrials.gov, including complete descriptions, criteria, outcomes, and locations.
About this study
Background: Crohn s disease (CD) is an inflammatory bowel disease. It causes inflammation of the gut. Symptoms may include diarrhea, abdominal pain, fatigue, weight loss and malnutrition. CD has no cure, but symptoms can sometimes be controlled with medicine. Researchers want to see if it is safe to treat CD with the medicine vorinostat. It is thought that vorinostat may reduce the inflammation process of CD. This may then help to relieve symptoms of CD. Participants who respond to Vorinostat will be invited to an extension phase of treatment with Vorinostat and possibly a maintenance treatment using Ustekinumab. Objectives: To see if vorinostat is safe for people with moderate-to-severe CD. To see if it is safe for people with moderate-to-sever CD to receive maintenance therapy using Ustekinumab after successful treatment of Vorinostat. Eligibility: Adults 18-65 with moderate-to-severe CD that medicine is not controlling. Design: Phase I is screening. It may last 120 days. Participants will have: Physical exam Medical history Tests of blood, urine, and stool samples Heart test Questionnaires Tuberculosis skin test They may have a colonoscopy and lymphapheresis collection. These will be explained in a separate consent. They will keep a diary of symptoms. Phase II is treatment using Vorinostat. It will take 12-13 weeks. Participants will take the study drug by mouth twice daily for 12 weeks. They will get a weekly phone call to talk about how the drug makes them feel. They will have blood taken regularly. Every 4 weeks, they will have a check-up that will repeat some screening tests. Phase III extension treatment of Vorinostat for an additional 6 months for those who respond to vorinostat and it is safe for them to continue treatment. Participants will continue to receive weekly calls to talk about how the drug makes them feel. They will have blood taken regularly. Every 3 months, they will have a check-up that will repeat some screening tests. Phase IV: is maintenance therapy for 2 years with Ustekinumab. Participants will receive a one time loading dose of ustekinumab, and then will receive the approved maintenance dose once every 8 weeks, at which time they will return to the NIH Clinical Center for evaluation. The participant will get a phone call 3 days after each dose and again 2 weeks later to see how the drug makes them feel. After two years of receiving treatment with ustekinumab the participant will have an end of study visit, where some of the screening tests, including a colonoscopy, will be repeated....
Inflammatory bowel disease (IBD), comprised of Crohn s disease and Ulcerative colitis, are chronic, life-long conditions characterized by relapsing inflammation of the gastrointestinal (GI) tract. Despite recent advances in IBD therapeutics, a significant number of patients with IBD continue to have significant symptoms. Chronic granulomatous disease (CGD) is a rare primary immunodeficiency, due to a mutation in one of the 5 genes encoding the phagocyte NADPH oxidase, and inability to generate reactive oxygen species (ROS) and in turn leads to dysregulated inflammation as ROS production is required for normal innate immune function but also plays a role in regulating inflammation Almost 50% of individuals with CGD develop intestinal inflammation, ranging from mild dysmotility to severe IBD. In prior studies, it has been demonstrated that epigenetic modifications of the genome are associated with and may contribute to the pathogenesis of various disease entities. One type of epigenetic modification involves acetylation and deacetylation of histones, mediated by histone acetyl transferases (HATs) and histone deacetylases (HDACs). Acetylation and deacetylation of histones regulate the affinity of histones for DNA, thus modulating the accessibility of transcription factors to gene promoters and enhancer sites. Of interest in this context is evidence that epigenetic modifications brought about by HDAC inhibitors (HDACi), i.e., agents that cause hyperacetylation of histones, can limit the course of gastrointestinal inflammation. One naturally occurring HDAC inhibitor, the bacterial product butyrate, has been shown to have effects on gene transcription that regulate potentially deleterious pro-inflammatory responses to microbiota in the gut environment. It has been shown that treatment of dendritic cells and macrophages with butyrate leads to down-regulation of lipopolysaccharide induced proinflammatory mediators such as nitric oxide, IL-6 and IL-12. In addition, butyrate has been shown to enhance the differentiation of intestinal Foxp3-positive T cells (T regulatory T cell (Treg) development that then modulates GI inflammation and contributes to mucosal homeostasis. Along the same lines, another HDAC inhibitor, vorinostat, has been shown to ameliorate graftvs-host disease (GVHD) affecting the GI tract in patients undergoing allogeneic bone marrow transplantation. This anti-inflammatory effect was also attributable to increased Treg activity, suggesting that vorinostat, like butyrate, decreases inflammation by enhancing the activity of cells with the capacity to down-regulate immune responses. The effect of vorinostat on Treg cell expansion in this study was particularly notable because it suggested that Treg cell numbers can be increased by agents that have an intrinsic effect on the transcription of key Treg cell transcription factors. On this basis, treatment of patients with inflammatory and autoimmune diseases by influencing Treg cell numbers may be a more effective than alternative existing methods of inducing Treg cell expansion such as administration of purified Tregs. In this protocol we propose a proof-of-concept clinical trial to study the safety and efficacy of vorinostat (100 mg PO BID for 36 weeks) in treating 20 individuals with moderate-to-severe CD, UC, or CGD colitis who have not been controlled by standard maintenance therapy. This will be accomplished in Phase II (12 weeks of treatment) and Phase III (36 weeks of treatment). We will assess the effectiveness of vorinostat by evaluating changes in symptom scores, endoscopic/histologic findings, and immunologic/laboratory parameters. The participant will return to the NIH Clinical Center (CC) after starting treatment on week 4, week 8, and week 24 for assessment of safety labs and testing of clinical response. On Week 12 and week 36 participants will return to the NIH CC for assessment of safety labs and testing of clinical and immunologic response. In IBD, 10-15 % of patients require surgery within 10 years of diagnosis with about 20-30% of patients ultimately requiring surgery due to failure of medical management . Therefore, the approach to treatment must also evolve from induction control of symptoms to preventing progression of the disease with maintenance therapy. Thus, the current paradigm has moved beyond treatment of just clinical symptoms to address inflammatory activity early on in the disease process and effectively down-modulate these pathways before irreversible intestinal damage and disability occur. The treatment goal is for patients to achieve a clinical response of symptoms but also subsequent development of clinical remission with the long term goal of optimizing treatment to have patients achieve a sustained clinical remission with endoscopic mucosal healing (STRIDE Committee). Thus, treatments that safely maintain long-term remission are essential. Treatment guidelines for CD and UC recommend maintenance therapy after remission is achieved, particularly for moderate-to-high risk patients. Potential benefits include reduction in hospitalization and surgery and improved quality of life. Long-term efficacy has been studied with azathioprine/mercaptopurine, methotrexate tumor necrosis factor (TNF) antagonists, vedolizumab. Although TNF antagonists have significantly advanced the care of CD and UC, their efficacy is limited and the development of anti-drug antibodies is associated with loss of response in maintenance therapy. In addition, potential significant side effects of maintenance treatments include bone marrow suppression, malignancy, and serious infections. Therefore, a need exists for safer agents that have demonstrated improved long-term maintenance efficacy. The gut inflammation complicating Crohn s disease has been characterized as a T helper type 1 (Th1)/T helper type 17 (Th17) inflammatory response, with excess IL-12, IL-23 cytokine production leading to the generation of excessive IFNgamma and IL-17. In comparison, the intestinal inflammation observed in UC can be characterized as a mixed T helper 2/Th17/Th1 response with predominately excess IL-13 and IL-17 excess but IFN-gamma can also be observed albeit decreased in levels opposite to CD patients. Intestinal inflammation observed in CGD colitis is typically chronic, relapsing, and difficult to manage. CGD colitis has some degree of association with CD and UC, as it is characterized by an increased secretion of inflammatory cytokines such as IFNgamma, IL-17 and IL-6. Glucocorticoids can be effective but often require addition of steroid-sparing agents such as purine antimetabolites, 5-aminosalicylates or other immunomodulators such as methotrexate cyclosporine, (Rosh et al. 1995), anakinra (Hahn et al. 2015), vedolizumab, and anti TNF alpha agents all with limited success. Most important, although decreased inflammatory responses can be observed with anti-TNF alpha therapy it is not without risk in these patients as TNFblockade therapy has led to life threatening infections. Ustekinumab, a monoclonal antibody to the p40 subunit of IL-12 and IL-23, is currently FDA approved for the treatment of moderate to severe plaque psoriasis, active psoriatic arthritis, moderately to severely active CD and ulcerative colitis Prior clinical trials have demonstrated long-term efficacy and safety profile of ustekinumab in psoriasis. Similarly, the long-term efficacy and safety of ustekinumab in CD dosing had been established in the UNITI trial studies (up to 44 week treatment) in patients who have failed TNF antagonists or other conventional therapy. These studies demonstrated significant response rates and induction of remission rates with a positive safety profile. In a phase 3 trial of IL-12 p40 monoclonal antibody in patients with moderate-to-severe UC, ustekinumab was found to be effective than placebo in achieving induction of clinical remission at 8 weeks. This effect was also observed in patients with or without previous treatment failure with other biologic agents. Studies addressing long term maintenance efficacy of ustekinumab in patients that are in remission are limited. In a prior retrospective review of CGD patients that received ustekinumab for CGD colitis at the NIH, nine patients were summarized. Six patients were reported with a clinical response and four patients achieved clinical remission. No long-term maintenance efficacy studies have been performed. In the present protocol (Phase IV), CD, UC, or CGD colitis patients that have achieved either a defined clinical response or are in remission with vorinostat will then be enrolled to receive long term maintenance treatment with ustekinumab. Participants will receive a weight-based IV loading dose of ustekinumab (see section 5.5) followed by administration of maintenance doses of 90 mg subcutaneously (SC) every 8 weeks with participants followed over a 2-year period.
Study design and administration
- Organization
- National Institutes of Health Clinical Center (CC)
- Organization class
- Nih
- Organization study ID
- 170101
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Sponsor class
- Nih
- Enrollment type
- Estimated
- Allocation
- Non Randomized
- Intervention model
- Single Group
- Primary purpose
- Treatment
- Masking
- None
- Who is masked
- Not provided
- Standard age groups
- Adult, Older Adult
Study arms
Experimental
1
participants will receive Vorinostat 100mg PO BID for 12 weeks
Interventions: Drug: Vorinostat
Experimental
2
participants will receive Vorinostat 100mg PO BID for 6months
Interventions: Drug: Vorinostat
Active Comparator
3
participants will receive ustekinumab (weight base induction dose followed by 90mg SC every 8 weeks for 24 months)
Interventions: Drug: Ustekinumab
Interventions
Drug
Vorinostat
It is a histone deacetylase (HDAC) inhibitor indicated for the treatment of cutaneous manifestations in patient with cutaneous T-cell lymphoma (CTCL) who have progress, persistent or recurrent disease on or following two systemic therapies. We are using this drug off label for the purpose of this study
Drug
Ustekinumab
Ustekinumab inhibits the bioactivity of human IL-12 and IL- 23 by preventing these cytokines from binding to the IL- 12Rbeta1 receptor protein expressed on the surface of immune cells. It is FDA approved for the treatment of adult patients with active psoriatic arthritis and more recently, in September 2016, ustekinumab has been approved for the treatment of patients with Crohn s disease.
Eligibility
18 Years–65 Years
All
Not accepted
Inclusion criteria (17)
- Individuals with moderate-to-severe CD, UC, and CGD colitis who are not controlled by and refractory to standard therapy will be eligible for inclusion into this study if they meet the following criteria:Registry-derived · unreviewed
- Are 18 to 65 years of age, inclusive, at enrollment date.Registry-derived · unreviewed
- Have a diagnosis of CD, UC, or CGD colitis that has been endoscopically or radiographically confirmed. A colonoscopy will be required at baseline to document mucosal disease activity. SES-CD for CD and CGD colitis will be obtained with minimum score of 7 and MES for UC patients will be obtained with minimum score of 2.Registry-derived · unreviewed
- Have active CD symptoms as defined by a CDAI score between 220 and 350, UC symptoms defined by a Mayo score of 6 to 10 (moderate) or 10 to 12 (severe), or CGD colitis symptoms defined as an HBI score of 8-16 (moderate) or \> 16 (severe), and demonstrate active symptoms as defined by continued weight loss, abdominal pain and/or diarrhea not controlled by standard therapy.Registry-derived · unreviewed
- The participant must have active CD and UC symptoms (as noted above) and therefore have had an inadequate response to, loss of response to, or intolerance to at least 1 of the following agent groups in control of their disease (as defined below for each individual agent group: Corticosteroids or Immunomodulators or TNF-alpha antagonists or Anti-integrin antibodies or JAK inhibitors or IL-12p19 (IL-23) antagonists). No specific induction therapy or long-term treatment for CGD colitis patients has been defined; therefore all symptomatic patients will be evaluated for inclusion on individual basis.Registry-derived · unreviewed
- CorticosteroidsRegistry-derived · unreviewed
- Signs and symptoms of persistently active disease despite a history of at least one 4-week induction regimen that included a dose equivalent to prednisone \>=30 mg PO once daily (QD) for 2 weeks or intravenously (IV) for 1 week ORRegistry-derived · unreviewed
- ii. One failed attempt to taper corticosteroids to below a dose equivalent to prednisone 10 mg PO QD or to taper to below a dose of 9 mg of budesonideRegistry-derived · unreviewed
- ORRegistry-derived · unreviewed
- iii. History of intolerance of corticosteroids at the discretion of the principal investigator (PI) (including but not limited to Cushing s syndrome, osteopenia/osteoporosis, hyperglycemia, insomnia, or infection)Registry-derived · unreviewed
- ImmunomodulatorsRegistry-derived · unreviewed
- Signs and symptoms of persistently active disease despite a history of at least one 12-week regimen of oral azathioprine (AZA) (\>= 2.5 mg/kg/Day) or 6-MP (\>= 1.5 mg/kg/Day) ORRegistry-derived · unreviewed
- ii. Signs and symptoms of persistently active disease despite a history of at least one 12-week regimen of MTX (\>= 25 mg/week) ORRegistry-derived · unreviewed
- iii. History of intolerance of at least one immunomodulator (including but not limited to nausea/vomiting leading to discontinuation, abdominal pain, pancreatitis, liver function test abnormalities, lymphopenia, thiopurine methyltransferase genetic mutation, or serious infection)Registry-derived · unreviewed
- TNF-alpha antagonists with signs and symptoms of persistently active disease despite a history of receiving infliximab, adalimumab, or certolizumab at a dose approved for the treatment of CD or UC and:Registry-derived · unreviewed
- Patient had an inadequate response after completing the full induction regimen, per approved product labelingRegistry-derived · unreviewed
- ii. Responded initially but then lost response with continued therapyRegistry-derived · unreviewed
Exclusion criteria (71)
- Anti-integrin antibodies:Registry-derived · unreviewed
- with signs and symptoms of persistently active disease despite a history of receiving an anti-integrin antibody agent (natalizumab or vedolizumab) at a dose approved for the treatment of CD or UC and:Registry-derived · unreviewed
- Patient had an inadequate response after completing the full induction regimen, per approved product labelingRegistry-derived · unreviewed
- ii. Responded initially but then lost response with continued therapyRegistry-derived · unreviewed
- JAK inhibitor:Registry-derived · unreviewed
- with signs and symptoms of persistently active disease despite a history of receiving a JAK inhibitor (tofacitinib and ruxolitinib) at a dose approved for the treatment of CD or UC and:Registry-derived · unreviewed
- Patient had an inadequate response after completing the full induction regimen, per approved product labelingRegistry-derived · unreviewed
- ii. Responded initially but then lost response with continued therapyRegistry-derived · unreviewed
- Anti-IL-12 p19 (IL-23) antibodies:Registry-derived · unreviewed
- with signs and symptoms of persistently active disease despite a history of receiving an anti-IL-12p19 (IL-23) antibody agent (Skyrizi and Tremfya) at a dose approved for the treatment of CD or UC and:Registry-derived · unreviewed
- Patient had an inadequate response after completing the full induction regimen, per approved product labelingRegistry-derived · unreviewed
- ii. Responded initially but then lost response with continued therapyRegistry-derived · unreviewed
- At the discretion of the PI, concomitant medications will be permitted if the following conditions are met prior to baseline assessment (Day-1):Registry-derived · unreviewed
- 5-aminosalicylic acid (ASA)-based compounds are permissible if:Registry-derived · unreviewed
- Oral 5-ASA-based compounds must be at a stable dose for at least 3 weeks prior to baseline orRegistry-derived · unreviewed
- ii. Recently discontinued oral 5-ASA-based compounds must have been discontinued at least 3 weeks prior to baseline orRegistry-derived · unreviewed
- iii. Rectal 5-ASA-based compounds are not permissible during the study and must have been discontinued at least 3 weeks prior to baseline.Registry-derived · unreviewed
- Corticosteroids (e.g., prednisone, budesonide) are permissible if:Registry-derived · unreviewed
- Oral corticosteroids must be at a prednisone-equivalent dose of \<= 40 mg/day, or 9 mg/day of budesonide, and have been at a stable dose for at least 3 weeks prior to baseline orRegistry-derived · unreviewed
- ii. Discontinuation of oral corticosteroids must have been completed at leastRegistry-derived · unreviewed
- 3 weeks prior to baseline orRegistry-derived · unreviewed
- iii. Parenteral (subcutaneous, intramuscular, or IV) or rectal corticosteroids are not permitted during the study and must not have been used within a 3- week period prior to baselineRegistry-derived · unreviewed
- CD, UC, or CGD colitis-specific antibiotics are permissible if using an antibiotic for treatment of CD,UC, or CGD colitis (i.e., metronidazole, ciprofloxacin, rifaximin, ampicillin, sulfonamide and tetracycline)Registry-derived · unreviewed
- Participants must have been using the antibiotic for at least 3 weeks before baseline at a stable dose orRegistry-derived · unreviewed
- ii. If not currently using a CD, UC, or CGD colitis-specific antibiotic, the stop date must have been at least 3 weeks prior to baseline.Registry-derived · unreviewed
- Immunomodulators are permissible if:Registry-derived · unreviewed
- Participants receiving chronic (i.e., \>= 12 weeks) treatment with AZA, 6- MP, or MTX prior to baseline must be on a stable dose for at least 6-8 weeks prior to baseline and must continue on this same dose during the study. ORRegistry-derived · unreviewed
- ii. Participants who have discontinued therapy with AZA, 6-MP, or MTX must have stopped the medication at least 4 weeks prior to baseline. ORRegistry-derived · unreviewed
- iii. Participants must not have received therapy with other known immunomodulators (e.g. cyclosporine, tacrolimus, sirolimus, pentoxifylline, or mycophenolate mofetil) or experimental agents (e.g. granulocyte- or macrophage colony stimulating factor) for at least 8 weeks or 5 half-lives of agent from baseline, whichever is longer.Registry-derived · unreviewed
- The use of Anti-TNF, Anti-integrin, JAK inhibitors, Anti-IL-12p19 (IL-23) therapy or other biological therapy listed below will not be permitted and the following washout period will be required in order for participant to be eligible:Registry-derived · unreviewed
- Three months washout prior to baseline for certolizumab or natalizumab.Registry-derived · unreviewed
- ii. Two months washout prior to baseline for adalimumab, infliximab, and vedolizumab, tofacitinib, ruxolitinib, Skyrizi and Tremfya.Registry-derived · unreviewed
- iii. 8-week washout prior to baseline for cyclosporine, pimecrolimus, tacrolimus, and any other systemic immunosuppressant.Registry-derived · unreviewed
- 6\. Participants must have a primary medical care provider.Registry-derived · unreviewed
- 7\. Male participants must agree to employ birth control measures to prevent pregnancy in female partners from start of treatment and continuing through 3 months post treatment.Registry-derived · unreviewed
- 8\. Females of childbearing potential must not be breast-feeding, possibly or actually pregnant, must not have had unprotected intercourse for one month prior to dosing, and must agree not to become pregnant beginning from enrollment in the study to at least 6 months after the end of treatment. Participants must remain completely abstinent of potentially reproductive sexual intercourse (e.g. due to a committed lifestyle) or to consistently use BOTH a barrier method with a spermicide (male or female condom) AND ALSO one of the below listed methods of birth control:Registry-derived · unreviewed
- Continuous/daily hormonal methods including oral contraceptive pills, patch, implant/injection, etc.Registry-derived · unreviewed
- Surgical sterilization of either partner, of sufficient duration to be effective, and NOT known to have failed.Registry-derived · unreviewed
- Intrauterine device.Registry-derived · unreviewed
- Individuals who meet ANY of the following criteria will be excluded from participation in thisRegistry-derived · unreviewed
- Presence of clinically significant systemic infection (e.g., chronic or acute infection, urinary tract infection, or upper respiratory tract infection) within three months of screening.Registry-derived · unreviewed
- History or presence of recurrent or chronic infection (e.g., viral infection \[including hepatitis B (HBV), hepatitis C (HCV), human immunodeficiency virus (HIV)\], bacterial infection, systemic fungal infection, or syphilis).Registry-derived · unreviewed
- Positive for tuberculosis (TB) via QuantiFERON-Gold (QFT-G). Individuals who are known to have received the tuberculosis vaccine will be administered the QFT-G. Patients cannot have received tuberculosis vaccine within 12 months prior to start of study and cannot receive tuberculosis vaccine while on study or within 12 months from the time of conclusion of study participation.Registry-derived · unreviewed
- Has a history of active tuberculosis (TB) or a chest x-ray (CXR) with findings suggestive of old TB infection including calcified nodular lesions, apical fibrosis, or pleural scarring), acute or chronic HBV, HCV, HIV, or opportunistic infections.Registry-derived · unreviewed
- A conduction abnormality on baseline electrocardiogram (ECG) that in the opinion of a cardiologist, is deemed significant.Registry-derived · unreviewed
- At the discretion of the principal investigator, off-label use of any small molecule therapeutics that are immune modulators (e.g., naltrexone) within 90 days of beginning screening or at any time during the last 30-days of the screening window.Registry-derived · unreviewed
- Presence of abnormal hematological and biochemical parameters, including:Registry-derived · unreviewed
- Neutrophil count \< 1500 cells/mm3Registry-derived · unreviewed
- Hemoglobin \< 9 g/dLRegistry-derived · unreviewed
- Platelet count \<= 150,000 cells/mm3Registry-derived · unreviewed
- Creatinine \>= 1.2 times the upper limit of normal (ULN)Registry-derived · unreviewed
- Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) \>= 1.5 timesRegistry-derived · unreviewed
- ULNRegistry-derived · unreviewed
- Prothrombin time-international normalized ratio (PT-INR) \> 1.0 ULNRegistry-derived · unreviewed
- Serum bilirubin level \> 1.0 times ULNRegistry-derived · unreviewed
- Individuals on chronic anticoagulation medications.Registry-derived · unreviewed
- Stool sample positive for GI pathogens potentially causing disease (as assessed by FilmArray GI panel for 22 viral, bacterial, and parasitic organisms that can cause infectious diarrhea \[GI pathogen panel\]). The principal investigator will consult with an infectious disease specialist to review results and decide whether treatment is warranted.Registry-derived · unreviewed
- Presence of cytomegalovirus (CMV) infection as defined by positive immunohistochemical staining on tissue intestine biopsy.Registry-derived · unreviewed
- History of low-grade or high-grade colonic mucosal dysplasia.Registry-derived · unreviewed
- History of bowel surgery other than perianal (e.g., fistulotomy, seton placement, or abscess drainage) within 6 months prior to beginning the CDAI screening diary, Mayo scoring, or Harvey Bradshaw index or drawing screening blood samples.Registry-derived · unreviewed
- Presence of surgical changes to gut anatomy that preclude administration of clinical activity indices; this includes but is not limited to ileostomy, colostomy, or subtotal colectomy with ileorectal anastomosis.Registry-derived · unreviewed
- Known or suspected short bowel syndrome.Registry-derived · unreviewed
- Requirement of parenteral, total parenteral, elemental oral, or nasogastric nutrition.Registry-derived · unreviewed
- History or current evidence of cancer, other than non-melanomatous cancer of the skin, or participants that have undergone excision of basal cell carcinoma, squamous cell carcinoma of the skin. All patients receiving ustekinumab will be monitored for the appearance of non-melanoma skin cancer. Patients greater than 60 years of age, those with a medical history of prolonged immunosuppressant therapy and those with a history of PUVA treatment will be followed closely.Registry-derived · unreviewed
- Unwillingness or inability to comply with study requirements.Registry-derived · unreviewed
- Presence of only small bowel disease that is inaccessible by standard colonoscopy for harvest of research biopsies. Individuals with only upper gastrointestinal disease or only perianal fistulizing disease are also excluded for this reason.Registry-derived · unreviewed
- Refusal to abstain from using COX-2 inhibitors or non-steroidal anti-inflammatory drugs (NSAIDs) throughout the study agent administration period.Registry-derived · unreviewed
- Has uncontrolled diabetesRegistry-derived · unreviewed
- Is taking anti-seizure medication, such as valproic acid or its derivative (i.e., Depakote).Registry-derived · unreviewed
- Presence of any condition that, in the opinion of the principal investigator, contraindicates participation in this study.Registry-derived · unreviewed
- Has participated in another investigational trial within 8 weeks (or 5 half-lives of any investigational study agent), whichever is greater, prior to the pre-trial (screening) visit. The window will be derived from the last date of treatment on the previous trial.Registry-derived · unreviewed
This information can identify a possible match, conflict, or item needing confirmation. Only the study team can determine eligibility.
Study outcomes
Primary outcome
To evaluate the safety and tolerability of vorinostat in patients with moderate to severe CD as measured by the rate, frequency, and severity of adverse events (AEs) after 12 weeks of treatment.
Time frame: Days 28, 56 and 12 and 24 weeks after start of treatment
This is assessing safety issue
Secondary outcome
170 or greater score on IBDQ
Time frame: end of Phase III
Change in Inflammatory Bowel Disease Questionnaire (IBDQ) score from baseline and proportion of participants with a total score of 170 or greater in response to vorinostat.
Secondary outcome
Determine safety and tolerability of ustekinumab maintenance
Time frame: end of study
To determine if ustekinumab is safe and tolerated in CD patients that have received treatment with vorinostat as measured by the rate, frequency, and severity of adverse events (AEs).
Secondary outcome
Mucosal healing from use of Vorinostat
Time frame: end of Phase III
To determine the number of participants with mucosal healing, as assessed by a decrease in endoscopic scores from baseline to zero (Simple Endoscopic Score Crohn s Disease \[SES-CD\] for CD) or the number of participants with mucosal response as assessed by a decrease from baseline in SES-CD by 50% in response to vorinostat
Secondary outcome
Changes in CDAI score equal to or greater than 70
Time frame: weeks 12 and 24
To determine the number of participants participants that achievea clinical response at week 12 and week 36, as defined by a decrease in CDAI from baseline by greater than or equal to 70 points for CD patients, upon completion of study Phase II and Phase III
Secondary outcome
Acheive clinical remission
Time frame: weeks 12 and 24
To determine the number of participants that achieve clinical remission at Week 12 and week 36 as defined by a CDAI score of 150 points or less, upon completion of study Phase II and Phase III.
Secondary outcome
Mucosal healing after ustekinumab maintenance
Time frame: end of study
To determine the number of participants with mucosal healing, as assessed by a decrease in endoscopic scores from baseline (vorinostat therapy at week 36) to zero in response to ustekinumab (Simple Endoscopic Score Crohn s Disease \[SES-CD\] for CD) or the number of participants with mucosal response as assessed by a decrease from baseline in SES-CD by 50% in response to ustekinumab upon completion of Phase IV.
Secondary outcome
Achieve continued remission with ustekinumab
Time frame: end of study
To determine the number of participants that achieve either a continued remission (CDAI \< 150) or response after vorinostat therapy at week 36 as defined by a decrease in CDAI from baseline by greater than or equal to 70 points in response to ustekinumab upon completion of Phase IV.
Recruiting locations in the United States
National Institutes of Health Clinical Center
RecruitingBethesda, Maryland, 20892, United States
For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)800-411-1222prpl@cc.nih.gov
Central study contacts
Registry dates
- First posted
- May 30, 2017
- Primary completion
- Jun 30, 2035
- Overall completion
- Jun 30, 2035
Trial information comes from ClinicalTrials.gov and may change. Confirm current status, eligibility, and site details with the study team. Aidy does not provide medical advice or determine eligibility.