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

NCT ID: NCT03716388

Last Updated: 2019-02-12

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-01
• Study Completion Date: 2019-12-01

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.

Detailed Description

This will be a prospective randomised placebo-controlled trial. Newly diagnosed treatment naive patients with mild to moderately severe UC will be recruited (n=15). The patients will be randomized into 3 groups; i.e group I (n=5): FMT with placebo, group II (n=5): FMT with mesalamine, group III (n=5): Placebo infusion with mesalamine. The patients will undergo colonoscopic administration of fecal slurry (groups I and II) or placebo (group III) at weeks 0,2,6,10 and 14. Mesalamine will be administered in a dose of 4g/day. In case of clinical worsening during the study, a short course of steroids will be added. The primary end point will be clinical remission (Mayo score ≤2, all subscores ≤ 1) at week 14. Secondary end points will be achievement of endoscopic remission (endoscopic Mayo score 0) and histological remission (Nancy grade 0, 1) at the end of 14 weeks.

Conditions

Ulcerative Colitis Chronic Mild; Ulcerative Colitis Chronic Moderate

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

FMT Vs Placebo

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

Group Type: EXPERIMENTAL

Fecal Microbiota Transplantation

Intervention Type: 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.

Placebo granules

Intervention Type: OTHER

Granules resembling mesalamine granules, 4 grams a day

FMT Vs Mesalamine

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

Group Type: ACTIVE_COMPARATOR

Fecal Microbiota Transplantation

Intervention Type: 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.

Mesalamine Granules

Intervention Type: DRUG

Mesalamine granules 4 grams a day

Placebo Infusion Vs Mesalamine

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

Group Type: ACTIVE_COMPARATOR

Mesalamine Granules

Intervention Type: DRUG

Mesalamine granules 4 grams a day

Placebo infusion

Intervention Type: OTHER

Water with food grade colour to resemble fecal slurry

Interventions

Fecal Microbiota Transplantation

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.

Intervention Type: BIOLOGICAL

Mesalamine Granules

Mesalamine granules 4 grams a day

Intervention Type: DRUG

Placebo infusion

Water with food grade colour to resemble fecal slurry

Intervention Type: OTHER

Placebo granules

Granules resembling mesalamine granules, 4 grams a day

Intervention Type: OTHER

Other Intervention Names

Rowasa

Eligibility Criteria

Inclusion Criteria

• Active UC:

1. UC diagnosed based on history of chronic (>4 weeks), inflammatory (with blood and mucous) diarrhoea

2. Total Mayo Score 4-10, Mayo endoscopic sub-score of >1

3. Histopathology suggestive of UC

• 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).

Exclusion Criteria

• 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

• High-risk sexual behaviors
• Communicable illnesses
• Antibiotic treatment within the past 3 months
• Intrinsic gastrointestinal illnesses such as irritable bowel syndrome, inflammatory bowel disease, gastrointestinal malignancies or major gastrointestinal surgical procedures
• Ongoing immune-modulator therapy for any concurrent illness
• Chronic pain syndromes
• Neurologic/neurodevelopmental disorders
• Metabolic syndrome
• Obesity (BMI >30 kg/m2)
• Malignant illnesses
• Donor's diet will be monitored with a diet diary.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Colitis & Crohn's Foundation (India)

UNKNOWN

Sponsor Role: collaborator

Dayanand Medical College and Hospital

OTHER

Sponsor Role: lead

Responsible Party

Ajit Sood

Professor and Head, Gastroenterology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ajit Sood, DM

Role: PRINCIPAL_INVESTIGATOR

Professor and Head Gastroenterology

Locations

Dayanand Medical College and Hospital

Ludhiana, Punjab, India

Site Status: RECRUITING

Countries

India

Central Contacts

Ajit Sood, DM

Role: CONTACT

ajitsood10@gmail.com

+919779497094

Facility Contacts

Ajit Sood, DM

Role: primary

Other Identifiers

2018-362

Identifier Type: -

Identifier Source: org_study_id