Fecal Microbiota Transplantation (FMT) in Treatment of Severe and Enduring Anorexia Nervosa

Safety and Efficacy of Fecal Microbiota Transplantation (FMT) in the Treatment of Severe and Enduring Anorexia Nervosa (SE-AN)

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).

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.

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