Ulcerative Colitis
Conditions
Keywords
ulcerative colitis
Brief summary
The purpose of this research study is to test the efficacy and safety of the study intervention, CurQD or placebo (non-active pill), in combination with vedolizumab prescribed as standard of care for patients with ulcerative colitis (UC)..
Detailed description
A prospective, 30-weeks long, treat-through, multi-center, parallel-group, double blind, placebo controlled, randomized pragmatic clinical trial to examine if there is added clinical benefit in participants with active UC receiving a combination VDZ+CurQD versus VDZ alone (with placebo). Moderately to severely active UC participants for whom VDZ was prescribed by their physician irrespective of the present trial as part of routine clinical care will be eligible. Moderate to severely active UC will be defined as a modified Mayo score of 5 to 9, with rectal bleeding score of ≥1, and with a sigmoidoscopy or colonoscopy sub-score of at least 2.
Interventions
DRUGCurQD
Capsule doses 235mg - 385mg curcumin/150mg-300mg QingDai
DRUGPlacebo
Matching capsules
DRUGVedolizumab
as prescribed by participant's provider as part of routine clinical care
Sponsors
Ryan C Ungaro
United States Department of Defense
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
participants are blinded
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Age 18 to 80 years old (inclusive) at time of consent * Understand and sign the written voluntary informed consent form prior to any protocol specific procedures * History of established UC for \>3 months as determined by standard clinical criteria * Active UC defined as a modified Mayo score of 5-9 with a rectal bleeding sub score \[RBS\] ≥1 and Mayo endoscopic score \[MES\] ≥2 * Participant will have a minimum disease extent of at least 5 cm proximal from the anal verge * Subjects must be on stable doses of concomitant medications, defined as: * Participants on oral corticosteroids must be on a stable dose \>2 weeks (dose not exceeding 20 mg/day prednisone, 9mg/day of budesonide, or equivalent) prior to screening * Participants on methotrexate (MTX), azathioprine (AZA), or 6-mercaptopurine (6-MP) must be on treatment at a stable dose \>4 weeks prior to screening and until end of study * Participants on oral 5-aminosalicylates, mesalamine, or sulfasalazine must be on a stable dose for \>4 weeks prior to screening and until end of study * Probiotics or anti-diarrheal at a stable dose ≥ 2 weeks prior to Screening and until the end of study * Participants who have been diagnosed with UC for ≥8 years must be up to date on their colorectal cancer screening per local guidelines by the time of randomization.
Exclusion criteria
* Diagnosis of inflammatory bowel disease unclassified (IBD-U) or Crohn's colitis * Previously received VDZ or etrolizumab (another anti-integrin biologic therapy) * Receiving corticosteroids at a dose \>20mg/day of prednisone within two weeks prior to enrollment * Participants who have been exposed to more than one advanced therapy medication (biologic or small molecule drug) before enrollment will be excluded * Receiving or planned concomitant biologic or small targeted small molecule advanced therapy (tumor necrosis factor antagonist, interleukin \[IL\]-12/23 antagonist, IL-23 antagonist, Janus kinase \[JAK\] inhibitor and/or sphingosine-1-phosphate \[S1P\] receptor modulator) with vedolizumab * Any calcineurin inhibitor use within 4 weeks prior to screening (e.g., cyclosporine, tacrolimus) * Participant with known hepatitis B or C infection * Participant with active or latent tuberculosis (that has not been adequately treated) * Participant has any active infection * Participant has fecal sample positive for enteric infection at screening * History of prior colectomy or ileal pouch anal anastomosis * Participants with fulminant UC, toxic megacolon, or hospitalized for UC currently or within prior 2 weeks * Severe lab abnormalities including hemoglobin \< 8.0 g/dl, albumin \< 3.0 g/dl, platelets \< 100/mcl, AST \> 2X upper limit of normal (ULN), ALT \>2X ULN, total bilirubin \>1.5X ULN * Participant with history of colon cancer or colonic dysplasia not adequately treated (i.e. polyp removed) * Any serious underlying disease other than UC that in the opinion of the investigator may interfere with the participant's ability to participate fully in the study or would compromise participant safety (such as any unstable or uncontrolled medical disorder, class III or IV congestive heart failure, demyelinating disease) * History of primary sclerosing cholangitis * Renal impairment and reduced creatinine clearance defined as estimated glomerular filtration rate GFR (eGFR)\<60mL/min * History of chronic liver disease (autoimmune hepatitis, cirrhosis, etc.) * Currently requiring total parental nutrition * History of solid organ transplantation * History of malignancy or lymphoproliferative disorder in the prior 5 years, other than * adequately treated localized carcinoma in situ of the cervix or nonmetastatic squamous * cell carcinoma, or nonmetastatic basal cell carcinoma of the skin. * History of venothromboembolism (DVT or PE) or known inherited or acquired hyper coagulation disorder * Currently taking anti-platelet agent (other than aspirin) or anti-coagulant (coumadin, * rivaroxaban, etc.) * History of human immunodeficiency virus (HIV) infection * Participant is pregnant or lactating or actively trying to become pregnant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with clinical remission | Week 14 | Clinical remission is defined as a modified Mayo score (mMS) of 2 or lower with stool frequency subscore of 0 or 1, rectal bleeding subscore of 0, and an endoscopic sub-score 0 or 1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with a clinical response | 14 weeks | Clinical response is defined as a decrease from baseline in the mMS of f ≥ 2 points and at least 30% reduction from baseline, and a decrease in RBS of ≥1 or an absolute RBS of 0 or 1. |
| Number of participants with corticosteroid-free remission | Week 30 | Corticosteroid-free remission at week 30 (end of maintenance phase of clinical trial) is defined as a mMS of 2 or lower with stool frequency sub-score of 0 or 1, rectal bleeding sub-score of 0, and an endoscopic sub-score of 0 or 1 without escalation of vedolizumab therapy (increase in dosing frequency) and without corticosteroid exposure for at last 8 weeks prior to assessment. |
| Number of participants with endoscopic improvement | Week 14 and Week 30 | Endoscopic improvement at weeks 14 and 30 defined as a centrally read endoscopy sub-score of 0 or 1 (score of 1 excludes friability). The endoscopic subscore is part of the Mayo Endoscopic Score (MES). The MES endoscopic subscore is graded: * 0\. No friability or granularity, intact vascular pattern * 1\. Mild-erythema, diminished or absent vascular markings, mild granularity * 2\. Moderate-marked erythema, absent vascular marking, granularity, friability, no ulceration * 3\. Severe-marked erythema, absent vascular markings, granularity, friability, spontaneous bleeding in the lumen, ulcerations |
| Number of participants with endoscopic remission | Week 14 and Week 30 | Endoscopic remission at weeks 14 and 30 defined as a centrally read endoscopy sub-score of 0. The endoscopic subscore is part of the Mayo Endoscopic Score (MES). The MES endoscopic subscore is graded: * 0\. No friability or granularity, intact vascular pattern * 1\. Mild-erythema, diminished or absent vascular markings, mild granularity * 2\. Moderate-marked erythema, absent vascular marking, granularity, friability, no ulceration * 3\. Severe-marked erythema, absent vascular markings, granularity, friability, spontaneous bleeding in the lumen, ulcerations |
| Number of participants with durable clinical remission | Week 14 and Week 30 | Durable clinical remission defined as clinical remission at both week 14 and 30. Clinical response is defined as a decrease in the mMS of ≥ 2 points and at least 30% reduction, and a decrease in RBS of ≥1 or an absolute RBS of 0 or 1. |
Countries
United States
Contacts
CONTACTNicole Lewis
CONTACTMiriam San Lucas
PRINCIPAL_INVESTIGATORRyan Ungaro, MD MS
Icahn School of Medicine at Mount Sinai
Outcome results
None listed