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

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ClinicalTrials.gov Identifier: NCT03716388
Recruitment Status : Recruiting
First Posted : October 23, 2018
Last Update Posted : February 12, 2019
Sponsor:
Collaborator:
Colitis & Crohn's Foundation (India)
Information provided by (Responsible Party):
Ajit Sood, Dayanand Medical College and Hospital

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.

Condition or disease Intervention/treatment Phase
Ulcerative Colitis Chronic Mild Ulcerative Colitis Chronic Moderate Biological: Fecal Microbiota Transplantation Drug: Mesalamine Granules Other: Placebo infusion Other: Placebo granules Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
Official Title: Fecal Microbiota Therapy Vs 5-aminosalicylates for Induction of Remission in Newly Diagnosed Mild-moderately Active UC : a Pilot Study
Actual Study Start Date : December 1, 2018
Estimated Primary Completion Date : December 1, 2019
Estimated Study Completion Date : December 1, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: FMT Vs Placebo
Fecal microbiota transplantation (fresh sample, colonoscopic administration at weeks 0,2,6,10,14) plus placebo granules (4g/day)
Biological: 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.

Other: Placebo granules
Granules resembling mesalamine granules, 4 grams a day

Active Comparator: FMT Vs Mesalamine
Fecal microbiota transplantation (fresh sample, colonoscopic administration at weeks 0,2,6,10,14) plus mesalamine granules (4g/day)
Biological: 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.

Drug: Mesalamine Granules
Mesalamine granules 4 grams a day
Other Name: Rowasa

Active Comparator: Placebo Infusion Vs Mesalamine
Placebo infusion (colonoscopic administration at weeks 0,2,6,10,14) plus mesalamine granules (4g/day)
Drug: Mesalamine Granules
Mesalamine granules 4 grams a day
Other Name: Rowasa

Other: Placebo infusion
Water with food grade colour to resemble fecal slurry




Primary Outcome Measures :
  1. Clinical remission [ Time Frame: Week 14 ]
    Mayo score ≤2, each subscore ≤1


Secondary Outcome Measures :
  1. Clinical response [ Time Frame: Weeks 0,2,6,10,14 ]
    Reduction of Mayo score ≥30% and ≥3 points compared to baseline

  2. Endoscopic remission [ Time Frame: Week 14 ]
    Endoscopic Mayo subscore 0

  3. Histological remission [ Time Frame: Week 14 ]
    Nancy grade 0 or 1



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

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
  • Inclusion criteria for donor

    • 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 for donor

    • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03716388


Contacts
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Contact: Ajit Sood, DM +919779497094 ajitsood10@gmail.com

Locations
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India
Dayanand Medical College and Hospital Recruiting
Ludhiana, Punjab, India, 141001
Contact: Ajit Sood, DM         
Sponsors and Collaborators
Dayanand Medical College and Hospital
Colitis & Crohn's Foundation (India)
Investigators
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Principal Investigator: Ajit Sood, DM Professor and Head Gastroenterology

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Responsible Party: Ajit Sood, Professor and Head, Gastroenterology, Dayanand Medical College and Hospital
ClinicalTrials.gov Identifier: NCT03716388     History of Changes
Other Study ID Numbers: 2018-362
First Posted: October 23, 2018    Key Record Dates
Last Update Posted: February 12, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Ajit Sood, Dayanand Medical College and Hospital:
Fecal Microbiota Transplantation
Ulcerative Colitis
Induction of Remission

Additional relevant MeSH terms:
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Colitis
Ulcer
Colitis, Ulcerative
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Inflammatory Bowel Diseases
Mesalamine
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents