An Open-Label, Proof of Consent Study of Vorinostat for the Treatment of Mdoerate-to-Severe Crohn s Disease and Maintenance Therapy With Ustekinumab

Recruiting now · Phase 1/Phase 2

Conditions studied: Crohn's Disease

In brief

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....

Key facts

Study ID

NCT03167437

Run by

National Institute of Allergy and Infectious Diseases (NIAID)

People needed

35

Starts

2017-10-30

Expected to finish

2035-06-30

Last updated by the study team

2026-08-04

Who can join

Age: 18 and older, up to 65. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

• Individuals who meet ANY of the following criteria will be excluded from participation in this
• study:
• 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.
• 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).
• 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.
• 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.
• A conduction abnormality on baseline electrocardiogram (ECG) that in the opinion of a cardiologist, is deemed significant.
• 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.
• Presence of abnormal hematological and biochemical parameters, including:
• Neutrophil count < 1500 cells/mm3
• Hemoglobin < 9 g/dL
• Platelet count <= 150,000 cells/mm3
• Creatinine >= 1.2 times the upper limit of normal (ULN)
• Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >= 1.5 times
• ULN
• Prothrombin time-international normalized ratio (PT-INR) > 1.0 ULN
• Serum bilirubin level > 1.0 times ULN
• Individuals on chronic anticoagulation medications.
• 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.
• Presence of cytomegalovirus (CMV) infection as defined by positive immunohistochemical staining on tissue intestine biopsy.
• History of low-grade or high-grade colonic mucosal dysplasia.
• 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.
• 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.
• Known or suspected short bowel syndrome.
• Requirement of parenteral, total parenteral, elemental oral, or nasogastric nutrition.

Where it is running

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (enrolling)

Full record on ClinicalTrials.gov

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