Clinical trial NCT03928808: Fecal Microbiota Transplantation (FMT) in Treatment of Severe and Enduring Anorexia Nervosa
Official title: Safety and Efficacy of Fecal Microbiota Transplantation (FMT) in the Treatment of Severe and Enduring Anorexia Nervosa (SE-AN)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: EARLY_PHASE1
Conditions: Anorexia Nervosa
Keywords: Fecal Microbiota Transplantation
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: OpenBiome
name: Foundation of Hope, North Carolina
First posted: 2019-04-26
Enrollment: 0
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open Label Pilot Study
Primary purpose: OTHER

Brief summary: This is an open-label pilot study designed to explore the safety, feasibility, tolerability, and acceptability of fecal microbiota transplantation (FMT) in the treatment of severe and enduring anorexia nervosa (SE-AN).

Detailed description: Open-label investigation of 10 individuals seeking inpatient treatment for severe and enduring anorexia nervosa. In addition to standard inpatient treatment, patients receive one FMT per week for 4 weeks, with follow-ups at 8 weeks and 6 months. Patients will receive 30 mL of healthy fecal microbial preparation (OpenBiome, FMP30) into the upper GI tract via a nasogastric tube weekly for 4 weeks. Primary outcomes are to determine safety, feasibility, tolerability, and acceptability of FMT for the treatment of AN. Secondary outcomes are: to determine preliminary efficacy as indexed by weight gain and weight retention over follow-up; to assess positive change in psychological metrics; to measure the efficiency of microbial transfer from the FMT material to the recipient intestinal microbiota; and to determine the duration of this effect via repeat stool sampling paired with 16S rRNA gene and/or shallow shotgun metagenomics.

Eligibility criteria: Inclusion Criteria:

* Provision of signed and dated informed consent form.
* Stated willingness to comply with all study procedures and availability for the duration of the study.
* Female aged 18-45.
* Diagnosed with SE-AN, defined here as having suffered from AN for five or more years and having participated in two or more inpatient or residential treatment programs followed by weight relapse.
* Sufficiently medically stable to receive FMT (serum electrolytes within normal limits, normal EKG)
* Willing to adhere to the FMT dosing regimen.
* For females of reproductive potential, in sexual relationships with men, must use an acceptable method of contraception from 30 days prior to enrollment until 4 weeks after completing study treatment.\* Participants must also be willing to be subjected to periodic pregnancy tests.
* Agreement to adhere to Lifestyle Considerations throughout study duration.
* Adequate insurance to cover inpatient stay.

  * Lifestyle Considerations: During this study, participants are asked to:

    * Participate in standard inpatient treatment at UNC-Chapel Hill's CEED.
    * Remain nil per os (npo) on the morning of each dosing session and for two hours after receiving FMT, on four individual instances of FMT administration.
    * Abstain from sexual activity or use a condom or other form of highly effective birth control during the 30-day active stage of the clinical trial.
    * Inform the research team as soon as possible if they become pregnant during the eight-week and six-month follow-up periods.
    * If a trial participant has begun a course of one of this trial's prohibited medications during the eight-week or six-month follow-up periods, participants will be asked only to report the name of the medication, dose, and duration of treatment.

Exclusion Criteria:

* Male or outside of the 18-45 range
* Previous FMT or microbiome-based products at any time excluding this study
* Patients with allergies to ingredients Generally Recognized As Safe (GRAS)
* Patients with a history of severe anaphylactic or anaphylactoid food allergy
* Patient received antibiotics in the last 48 hours. Patients will be eligible to enroll if antibiotic therapy is discontinued for at minimum 48 hours prior to start of study
* Requires continued antibiotic use or anticipates antibiotic use in the upcoming 4 weeks
* Concurrent intensive induction chemotherapy, radiation therapy, or biological treatment for active malignancy.
* Pregnancy or lactation
* Febrile illness within past month
* Treatment with another investigational drug within the past month
* Alcohol or drug dependence either at time of the study or within the last year
* Active gastrointestinal infection at time of enrollment
* Any gastrointestinal or potentially intestinal microbiota-related conditions, including: Severe gastroparesis (e.g., gastric pacemaker) and any history of gastrointestinal illness (including but not limited to inflammatory bowel disease, irritable bowel syndrome, celiac disease, any gastrointestinal cancer, etc.)
* Major gastrointestinal surgery (e.g. significant bowel resection) within 3 months before enrollment. This does not include appendectomy or cholecystectomy
* Type 1 or 2 diabetes mellitus
* Known or suspected toxic megacolon and/or known small bowel ileus
* History of total colectomy or bariatric surgery
* Solid organ transplant recipients less than or equal to 90 days posttransplant or on active treatment for rejection
* If at risk for CMV/EBV associated disease (at investigator's discretion, e.g. immunocompromised), negative IgG testing for cytomegalovirus (CMV) or Epstein-Barr Virus (EBV).
* Patients who are immunocompromised
* Unable or unwilling to comply with protocol requirements
* Expected life expectancy \< 6 months
* A condition that would jeopardize the safety or rights of the subject, would make it unlikely for the subject to complete the study, or would confound the results of the study

Primary outcomes:
measure: Proportion of Participants with Adverse Events (AEs)
timeFrame: Through day 30 (±3 days)
measure: Proportion of Participants with a Severe Adverse Event (SAE)
timeFrame: Through day 30 (±3 days)
measure: Number of Participants Recruited
timeFrame: 3 years
measure: Number of Participants Able to Complete 4 FMT Administrations
timeFrame: 3 years
measure: Number of Participants Reporting Acceptable Levels of GI distress Post FMT
timeFrame: Through Week 4
Secondary outcomes:
measure: Change in BMI Across Treatment and Follow-Up
timeFrame: Pre-Treatment through Follow-Up (Month 6)
measure: Change in Percent Body Fat Across Treatment and Follow-Up
timeFrame: Pre-Treatment through Follow-Up (Month 6)
measure: Eating Disorder Examination Questionnaire (EDE-Q) Scores over Time
timeFrame: Pre-Treatment through Follow-Up (Month 6)
measure: PHQ-9 Scores Over Time
timeFrame: Pre-Treatment through Follow-Up (Month 6)
measure: GAD-7 Scores Over Time
timeFrame: Pre-Treatment through Follow-Up (Month 6)
measure: PROMIS-GI Scores Over Time
timeFrame: Pre-Treatment through Follow-Up (Month 6)
Other outcomes:
measure: FMT Transfer Efficiency
timeFrame: Pre-Treatment through Follow-Up (Month 6)
Locations:
city: Chapel Hill
country: United States
facility: UNC Chapel Hill
state: North Carolina
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Mary Kimmel, MD
role: PRINCIPAL_INVESTIGATOR
References: