Evaluating the Combined Effect of Vedolizumab and Semi-Vegetarian Diet on Ulcerative Colitis.

NCT03309865 | Withdrawn Early Phase 1 DMC

• 1 other identifier: IRB 17-005613
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Research of fecal microflora and dysbiosis status in ulcerative colitis (UC) has shown its influential role on the disease pathogenesis. Vedolizumab, a humanized monoclonal antibody blocking the migration of leukocytes into inflamed intestinal tissue, has been shown to achieve remission in about half of active UC patients. Dietary intervention in UC patients has not been adequately studied. There is a significant clinical gap to achieve a higher efficacy and better clinical outcomes on the treatment of active UC patients. This study proposes to assess the integrated effect of normalization of intestinal dysbiosis through a structured semi-vegetarian dietary intervention in active UC patients who will also be under the standard of care medical therapy (vedolizumab). Significance of investigation for innovation: The pathogenesis of UC has been found to be multi-factorial, including host genetics and dysregulated inflammatory response, and recent research has shown the influential role of gut environmental factors - dysbiosis which has been found the key feature of UC. Vedolizumab has been shown effective (e.g. 47% clinical response rate vs. 25% in placebo group) and is part of the current standard of care treatment in UC. With the observation of drastic increase of IBD patients in Asia, in which has historically low incidence of IBD, it is generally accepted that the westernized diet and urbanization of life style play an important role in IBD pathogenesis. Enteral nutritional therapy has been demonstrated effective in pediatric Crohn's disease (CD) patients; however, the application to adult IBD patients has not been widely accepted partly because of the compliance issue. In addition, unlike CD, neither enteral nutrition nor non-enteral nutrition in patients with active UC has been adequately studied. Therefore, this study proposes a novel approach to assess the integrated effect of a structured dietary intervention in active UC patients who will also be under the current standard of care medical therapy (vedolizumab). After this study achieves the proposed primary or secondary outcome, it will further support the hypothesized synergistic interactive therapeutic effect between the normalization of dysbiosis in the intestine (through dietary intervention) and anti-inflammatory biologics (vedolizumab).

Conditions

Ulcerative Colitis; Dietary Modification

Keywords

semi-vegetarian diet; vedolizumab; ulcerative colitis

Outcome Measures

Primary Outcomes (1)

• Clinical response at week 6

  Clinical response at week 6 (which is defined as ≥3 improvement in Mayo score, and a decrease of at least 30% from the baseline score).

  6 weeks

Secondary Outcomes (1)

• Clinical response at week 14

  14 weeks

Study Arms (1)

Combined diet and vedolizumab

EXPERIMENTAL

Intervention: vedolizumab injection (300mg, IV infusions at week 0, 2, 6, 14) and concurrently on structured semi-vegetarian diet; Duration of Therapy: 14 weeks

Dietary Supplement: semi-vegetarian diet; Drug: Vedolizumab Injection

Interventions

semi-vegetarian diet DIETARY_SUPPLEMENT

semi-vegetarian dietary intervention: Duration of Therapy: 14 weeks;

Combined diet and vedolizumab

Vedolizumab Injection DRUG

vedolizumab (300mg) IV infusions at week 0, 2, 6, 14; Duration of Therapy: 14 weeks

Also known as: vedolizumab

Combined diet and vedolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years or older
• diagnosed with active UC (with a Mayo score ≥4, with an endoscopic Mayo Clinic score ≥1, and disease that extended 15 cm or more from the anal verge)
• failed with prior mesalamine therapy
• Patients who were previously exposed to mesalamine or steroids will have a 30-day washout period before being enrolled
• Patients who were previously exposed to tumor necrosis factor (TNF) antagonists will have a 60-day washout period before being enrolled
• For patients who were previously exposed to glucocorticoids, immunosuppressive medications (i.e., azathioprine, 6-mercaptopurine, or methotrexate), or TNF antagonists, a documentation of unsuccessful previous treatment (i.e., lack of response or unacceptable adverse events) is required
• A diagnosis of UC confirmed by biopsy obtained at the index colonoscopy or flexible sigmoidoscopy.

You may not qualify if:

• Patients who have been on semi-vegetarian diet before the trial will be excluded
• pregnancy or lactation
• an unstable or uncontrolled medical disorder
• an anticipated requirement for major surgery
• history of subtotal colectomy with ileorectostomy or colectomy with ileoanal pouch, Koch pouch, or ileostomy for UC, or planned bowel surgery
• unable to give informed consent
• current diagnosis of fulminant colitis or toxic megacolon, abdominal abscess, symptomatic colonic stricture, stoma
• disease limited to the rectum (ulcerative proctitis)
• current total parenteral nutrition
• positive Clostridium difficile stool assay
• history of an infection requiring intravenous antimicrobial therapy within 1 month or oral antimicrobial therapy within 2 weeks
• history of listeria, histoplasmosis, chronic or active hepatitis B or C infection, human immunodeficiency virus, immunodeficiency syndrome, untreated tuberculosis
• history of central nervous system demyelinating disease
• history of malignancy other than a successfully treated nonmetastatic cutaneous squamous cell or basal cell carcinoma or localized carcinoma in situ of the cervix, or evidence of dysplasia or malignancy on the screening colonoscopy/flexible sigmoidoscopy with biopsy
• Any of the following laboratory abnormalities during the screening period:

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

Location

MeSH Terms

Conditions

Colitis, Ulcerative

Interventions

vedolizumab

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Study Officials

• Ming-Hsi Wang, MD, PhD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 7, 2017
• First Posted: October 16, 2017
• Study Start: December 25, 2017
• Primary Completion: August 31, 2018
• Study Completion: December 31, 2018
• Last Updated: September 26, 2018

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)