Clinical trial NCT03716388: 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
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Ulcerative Colitis Chronic Mild
Ulcerative Colitis Chronic Moderate
Keywords: Fecal Microbiota Transplantation
Ulcerative Colitis
Induction of Remission
Lead sponsor: Dayanand Medical College and Hospital
Sponsor class: OTHER
Collaborators: name: Colitis & Crohn's Foundation (India)
First posted: 2018-10-23
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

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.

Primary outcomes:
measure: Clinical remission
timeFrame: Week 14
Secondary outcomes:
measure: Clinical response
timeFrame: Weeks 0,2,6,10,14
measure: Endoscopic remission
timeFrame: Week 14
measure: Histological remission
timeFrame: Week 14
Other outcomes:
Locations:
city: Ludhiana
country: India
facility: Dayanand Medical College and Hospital
state: Punjab
Study officials:
affiliation: Professor and Head Gastroenterology
name: Ajit Sood, DM
role: PRINCIPAL_INVESTIGATOR
References: