Clinical trial NCT03006809: Optimal Fecal Microbiota Transplant Dosing for Mild to Moderate Ulcerative Colitis
Official title: Optimal Fecal Microbiota Transplant Dosing for Mild to Moderate Ulcerative Colitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Ulcerative Colitis
Keywords: Ulcerative colitis
FMT
fecal transplant
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
First posted: 2016-12-30
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a prospective unblinded, randomized trial for the use of Fecal Microbiota Transplantation (FMT) for the treatment of Ulcerative Colitis (UC), in combination with or without antibiotic pretreatment.

Detailed description: This is a prospective open-label, randomized trial for the use of Fecal Microbiota Transplantation (FMT) for the treatment of Ulcerative Colitis (UC), in combination with or without antibiotic pretreatment.

This trial involves 11 study visits at UCSF in San Francisco, CA.

The routes of administration will be via colonoscopy for all subjects with maintenance therapy administered orally (i.e. using encapsulated FMT) for half of the subjects and per rectum by enema in the other half of the subjects. Additionally, the utility of pretreatment antibiotics will be assessed.

Eligibility criteria: Inclusion Criteria:

* Patients with history of mild to moderate Ulcerative Colitis confirmed by endoscopy and pathology.
* Total Mayo score 4-9, endoscopic subscore ≥1; patients who have not had endoscopic evaluation within one year of enrollment will have flexible sigmoidoscopy for evaluation.
* Age 18 - 64 and deemed otherwise healthy at the discretion of the investigator.
* Concurrent therapies with mesalamine (stable x 4 weeks), immunomodulators (stable x 3 months), and biologic agents (stable x 3 months) will be allowed to continue during study.
* If patient is on prednisone, the dose must be ≤ 10mg/day at the time of treatment and will be weaned by 2.5mg/week during the study period.

Exclusion Criteria:

* Severe or refractory UC defined as Mayo score ≥10, endoscopic disease activity score 3
* Untreated enteric infection (positive stool test for any of the following: Clostridium difficile, Salmonella, Shigella, Yersinia, Campylobacter, enteropathogenic E. coli or other enteric infection at the discretion of the investigator.
* History of colectomy
* Disease limited to distal proctitis
* Patients taking probiotics within 6 weeks of planned FMT therapy.
* Severe immunodeficiency, inherited or acquired (e.g. HIV, chemotherapy or radiation therapy)
* Patients with the following laboratory abnormalities: absolute neutrophil count (ANC) \< 1000 / µl, platelets \<50 x 10\^9 /L,, hemoglobin \<6.5 g/dL..
* History of anaphylaxis (severe allergic reaction) to food allergens (e.g. tree nuts, shellfish)
* Dysphagia (oropharyngeal, esophageal, functional, neuromuscular)
* History of recurrent aspiration episodes
* Documented severe gastroparesis
* Active intestinal obstruction
* Patients with renal insufficiency (GFR \< 50ml/min)
* Allergy to the following generally regarded as safe ingredients (GRAS): glycerol, acid resistant HPMC, gellan gum, cocoa butter, titanium dioxide
* Adverse event attributable to any previous FMT
* Allergy/intolerance to proton pump inhibitor therapy
* Allergy/intolerance to vancomycin, metronidazole, or neomycin.
* Non-steroidal inflammatory medications (NSAIDs) as long-term treatment, defined as use for at least 4 days a week each month.
* Cholestyramine use
* Any condition in which the investigator thinks the FMT treatment may pose a health risk (e.g. severely immunocompromised)
* Simultaneous participation in another interventional clinical trial
* Patients who are pregnant, breast feeding or planning pregnancy during study trial period.
* During the trial period until one week after the trial end: Non-use of appropriate contraceptives in females of childbearing potential (e.g. condoms, intrauterine device (IUD), hormonal contraception, or other means considered adequate by the responsible investigator) or in males with a child-fathering potential (condoms, or other means considered adequate by the responsible investigator during treatment) or well-founded doubt about the patient's cooperation
* Patients with any other significant medical condition that could confound or interfere with evaluation of safety, tolerability or prevent compliance with the study protocol at the discretion of the investigator
* Life expectancy \<6 months

Primary outcomes:
measure: The occurrence of a Serious Adverse event (SAE), solicited and unsolicited AE, new gastrointestinal medical condition and diagnoses from FMT treatment or new infection from FMT treatment
timeFrame: up to 1 year
measure: Steroid-free Clinical Remission at week 9 + endoscopic remission or response defined as total Mayo score ≤ 2 with all four sub-scores ≤ 1 and a ≥ 1 point reduction in endoscopy sub-score
timeFrame: 8 weeks post initial treatment
Secondary outcomes:
measure: Changes in microbiome with FMT therapy. Changes in the microbiome: assessed by frequent stool sampling for 16S rRNA analysis prior to each FMT therapy and after the last capsule/enema dose
timeFrame: up to 1 year
measure: Clinical Response: decrease in Mayo score by ≥ 3 points, decrease in bleeding subscore by ≥ 1, or absolute subscore of 0-1
timeFrame: 8 weeks post initial treatment
measure: Progression of disease defined by initiation of anti-TNF agents or Corticosteroids: Initiation of anti-TNF agents (such as infliximab, adalimumab, certolizumab, vedolizumab and steroids). Includes time gap until additional agents are started.
timeFrame: 2, 4 and 8 weeks post initial FMT
measure: Progression of disease defined by increase in dosages of current UC medications
timeFrame: 2, 4 and 8 weeks post initial FMT
measure: Progression of disease defined by time to colectomy
timeFrame: up to one year post initial FMT
measure: Time to death secondary to UC
timeFrame: up to one year post initial FMT
measure: Progression of disease defined by clinical flare (Time to next flare)
timeFrame: 2, 4 and 8 weeks post initial FMT
measure: Increase in Quality of Life (based on RAND SF-36 survey and score)
timeFrame: 8 weeks post initial FMT
measure: Changes in Mood/Depression Score (based on PHQ-9 survey and score)
timeFrame: 8 weeks post initial FMT
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF Division of Gastroenterology at Mount Zion
state: California
Study officials:
References:
citation: Smith BJ, Piceno Y, Zydek M, Zhang B, Syriani LA, Terdiman JP, Kassam Z, Ma A, Lynch SV, Pollard KS, El-Nachef N. Strain-resolved analysis in a randomized trial of antibiotic pretreatment and maintenance dose delivery mode with fecal microbiota transplant for ulcerative colitis. Sci Rep. 2022 Apr 1;12(1):5517. doi: 10.1038/s41598-022-09307-5.