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

Primary Purpose

Ulcerative Colitis Chronic Mild, Ulcerative Colitis Chronic Moderate

Status
Unknown status
Phase
Phase 3
Locations
India
Study Type
Interventional
Intervention
Fecal Microbiota Transplantation
Mesalamine Granules
Placebo infusion
Placebo granules
Sponsored by
Dayanand Medical College and Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ulcerative Colitis Chronic Mild focused on measuring Fecal Microbiota Transplantation, Ulcerative Colitis, Induction of Remission

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Dayanand Medical College and HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Active Comparator

Arm Label

FMT Vs Placebo

FMT Vs Mesalamine

Placebo Infusion Vs Mesalamine

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

Clinical remission
Mayo score ≤2, each subscore ≤1

Secondary Outcome Measures

Clinical response
Reduction of Mayo score ≥30% and ≥3 points compared to baseline
Endoscopic remission
Endoscopic Mayo subscore 0
Histological remission
Nancy grade 0 or 1

Full Information

First Posted
October 21, 2018
Last Updated
February 10, 2019
Sponsor
Dayanand Medical College and Hospital
Collaborators
Colitis & Crohn's Foundation (India)
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1. Study Identification

Unique Protocol Identification Number
NCT03716388
Brief Title
Fecal Microbiota Therapy Vs 5-aminosalicylates for Induction of Remission in Newly Diagnosed Mild-moderately Active UC
Official Title
Fecal Microbiota Therapy Vs 5-aminosalicylates for Induction of Remission in Newly Diagnosed Mild-moderately Active UC : a Pilot Study
Study Type
Interventional

2. Study Status

Record Verification Date
February 2019
Overall Recruitment Status
Unknown status
Study Start Date
December 1, 2018 (Actual)
Primary Completion Date
December 1, 2019 (Anticipated)
Study Completion Date
December 1, 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Dayanand Medical College and Hospital
Collaborators
Colitis & Crohn's Foundation (India)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ulcerative Colitis Chronic Mild, Ulcerative Colitis Chronic Moderate
Keywords
Fecal Microbiota Transplantation, Ulcerative Colitis, Induction of Remission

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare Provider
Allocation
Randomized
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
FMT Vs Placebo
Arm Type
Experimental
Arm Description
Fecal microbiota transplantation (fresh sample, colonoscopic administration at weeks 0,2,6,10,14) plus placebo granules (4g/day)
Arm Title
FMT Vs Mesalamine
Arm Type
Active Comparator
Arm Description
Fecal microbiota transplantation (fresh sample, colonoscopic administration at weeks 0,2,6,10,14) plus mesalamine granules (4g/day)
Arm Title
Placebo Infusion Vs Mesalamine
Arm Type
Active Comparator
Arm Description
Placebo infusion (colonoscopic administration at weeks 0,2,6,10,14) plus mesalamine granules (4g/day)
Intervention Type
Biological
Intervention Name(s)
Fecal Microbiota Transplantation
Intervention Description
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
Drug
Intervention Name(s)
Mesalamine Granules
Other Intervention Name(s)
Rowasa
Intervention Description
Mesalamine granules 4 grams a day
Intervention Type
Other
Intervention Name(s)
Placebo infusion
Intervention Description
Water with food grade colour to resemble fecal slurry
Intervention Type
Other
Intervention Name(s)
Placebo granules
Intervention Description
Granules resembling mesalamine granules, 4 grams a day
Primary Outcome Measure Information:
Title
Clinical remission
Description
Mayo score ≤2, each subscore ≤1
Time Frame
Week 14
Secondary Outcome Measure Information:
Title
Clinical response
Description
Reduction of Mayo score ≥30% and ≥3 points compared to baseline
Time Frame
Weeks 0,2,6,10,14
Title
Endoscopic remission
Description
Endoscopic Mayo subscore 0
Time Frame
Week 14
Title
Histological remission
Description
Nancy grade 0 or 1
Time Frame
Week 14

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ajit Sood, DM
Phone
+919779497094
Email
ajitsood10@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ajit Sood, DM
Organizational Affiliation
Professor and Head Gastroenterology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Dayanand Medical College and Hospital
City
Ludhiana
State/Province
Punjab
ZIP/Postal Code
141001
Country
India
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ajit Sood, DM

12. IPD Sharing Statement

Plan to Share IPD
Undecided

Learn more about this trial

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

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