Fecal Microbiota Therapy Vs 5-aminosalicylates for Induction of Remission in Newly Diagnosed Mild-moderately Active UC

NCT03716388 | Unknown Phase 3 DMC

• 1 other identifier: 2018-362
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Ulcerative colitis is a chronic idiopathic inflammatory disease of the colon that is characterized by abdominal pain and bloody diarrhea. The pathogenesis of UC involves a complex interplay of genetic factors, immune dysregulation and environmental triggers. Conventional therapies for UC (including 5-aminosalicylates, corticosteroids, azathioprine or 6-mercaptopurine and biologics) focus on altering the immune response by suppression of immune cells. However, the primary pathogenic mechanism underlying UC maybe gut microbiota dysbiosis and a dysfunctional intestinal barrier resulting in an aberrant host immune response. Several studies have shown reduced microbial diversity in UC patients with under representation of anti-inflammatory phyla (Bacteroides and Firmicutes), and a relative increase of pro-inflammatory phyla (Proteobacteria and Actinobacteria). Motivated by this, therapies targeting intestinal dysbiosis (prebiotics, probiotics, synbiotics and fecal microbiota transplant (FMT)) have thus been tried in patients with UC. Though several case series and subsequently four high quality randomized controlled trails have established the efficacy of FMT in induction of remission in active UC, all these studies have used it as an add-on therapy, along with the previously ongoing conventional therapies. The investigators aim to assess the safety and efficacy of FMT as the sole modality for induction of remission in patients with newly diagnosed active UC.

Conditions

Ulcerative Colitis Chronic Mild; Ulcerative Colitis Chronic Moderate

Keywords

Fecal Microbiota Transplantation; Ulcerative Colitis; Induction of Remission

Outcome Measures

Primary Outcomes (1)

• Clinical remission

  Mayo score ≤2, each subscore ≤1

  Week 14

Secondary Outcomes (3)

• Clinical response

  Weeks 0,2,6,10,14

• Endoscopic remission

  Week 14

• Histological remission

  Week 14

Study Arms (3)

FMT Vs Placebo

EXPERIMENTAL

Fecal microbiota transplantation (fresh sample, colonoscopic administration at weeks 0,2,6,10,14) plus placebo granules (4g/day)

Biological: Fecal Microbiota Transplantation; Other: Placebo granules

FMT Vs Mesalamine

ACTIVE COMPARATOR

Fecal microbiota transplantation (fresh sample, colonoscopic administration at weeks 0,2,6,10,14) plus mesalamine granules (4g/day)

Biological: Fecal Microbiota Transplantation; Drug: Mesalamine Granules

Placebo Infusion Vs Mesalamine

ACTIVE COMPARATOR

Placebo infusion (colonoscopic administration at weeks 0,2,6,10,14) plus mesalamine granules (4g/day)

Drug: Mesalamine Granules; Other: Placebo infusion

Interventions

Fecal Microbiota Transplantation BIOLOGICAL

Freshly passed stools (80 g) will be diluted with normal saline (200 ml) and homogenized using a blender, filtered, filled into 4 syringes (50 ml each) and used within 1 hour of preparation or 6 hours of passage of stools. Polyethylene glycol lavage will be done for bowel preparation and the slurry administered into the ileum and/or caecum by colonoscopy. Post FMT, recipients will be encouraged to retain the slurry for 4-6 hours. FMT sessions will be scheduled at weeks 0,2,6,10,14.

FMT Vs Mesalamine; FMT Vs Placebo

Mesalamine Granules DRUG

Mesalamine granules 4 grams a day

Also known as: Rowasa

FMT Vs Mesalamine; Placebo Infusion Vs Mesalamine

Placebo infusion OTHER

Water with food grade colour to resemble fecal slurry

Placebo Infusion Vs Mesalamine

Placebo granules OTHER

Granules resembling mesalamine granules, 4 grams a day

FMT Vs Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Active UC:
• UC diagnosed based on history of chronic (\>4 weeks), inflammatory (with blood and mucous) diarrhoea
• Total Mayo Score 4-10, Mayo endoscopic sub-score of \>1
• Histopathology suggestive of UC

You may not qualify if:

• Severe UC (Total Mayo 11-12, Endoscopic Mayo Score 3)
• Uncertainty about diagnosis of UC : Infective colitis/ Indeterminate Colitis/ Crohn's Colitis
• Associated irritable bowel syndrome (IBS)
• Past history of surgery or colorectal surgery
• Exposure to antibiotics or probiotics in the last 4 weeks
• Patients with evidence of infections like C. difficile, cytomegalovirus, HIV, parasitic infections or extra-intestinal infections requiring antibiotics.
• Significant cardiopulmonary co-morbidities (high risk for repeated colonoscopy)
• Pregnancy
• Refusal to consent for repeated colonoscopies.
• Donor
• Single donor (voluntary healthy individual) after informed consent
• No personal or family history of UC or any other autoimmune disease or malignancy
• Screened by stool microscopy and culture for common detectable enteric pathogens (Salmonella, Shigella, Campylobacter, Vibrio cholera, E. coli, Clostridium difficile, Giardia lamblia and Cryptosporidium) at the start of the study and every 4 weeks thereafter.
• Negative for antibodies against hepatitis A, C and E, hepatitis B surface antigen (HBsAg), syphilis and human immunodeficiency virus (HIV).
• High-risk sexual behaviors

Sponsors & Collaborators

• Dayanand Medical College and Hospital: lead
• Colitis & Crohn's Foundation (India): collaborator

Study Sites (1)

Dayanand Medical College and Hospital

Ludhiana, Punjab, 141001, India

RECRUITING

MeSH Terms

Conditions

Colitis, Ulcerative

Interventions

Fecal Microbiota Transplantation; Mesalamine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics; meta-Aminobenzoates; Aminobenzoates; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Aminosalicylic Acids; Salicylates; Hydroxybenzoates; Hydroxy Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenols

Study Officials

• Ajit Sood, DM

  Professor and Head Gastroenterology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ajit Sood, DM

CONTACT

+919779497094; ajitsood10@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Head, Gastroenterology

Study Record Dates

• First Submitted: October 21, 2018
• First Posted: October 23, 2018
• Study Start: December 1, 2018
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2019
• Last Updated: February 12, 2019

Record last verified: 2019-02

Locations

IN (1)