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

Study Overview
=================
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.

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

Conditions
-----------------
Anorexia Nervosa

Intervention / Treatment
-----------------
* Biological: Fecal Microbiota Transplantation (FMT)


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Interventional Model Description: Open Label Pilot Study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FMT for SE-AN<br>Inpatients at the UNC-Chapel Hill Center of Excellence for Eating Disorders (CEED) and will receive weekly fecal microbiota transplantations for four weeks. This will be in addition to standard care at CEED. | Biological: Fecal Microbiota Transplantation (FMT)<br>* Nasogastric administration of OpenBiome 25 g/mL solution administered nasogastrically once weekly for 4 consecutive weeks<br>* Other names: FMP30;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants with Adverse Events (AEs) | Safety 1 | Through day 30 (±3 days) | 
| Proportion of Participants with a Severe Adverse Event (SAE) | Safety 2 | Through day 30 (±3 days) | 
| Number of Participants Recruited | Feasibility 1, Ability to Recruit 10 Participants with SE-AN | 3 years | 
| Number of Participants Able to Complete 4 FMT Administrations | Tolerability 1 | 3 years | 
| Number of Participants Reporting Acceptable Levels of GI distress Post FMT | Tolerability 2 | Through Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in BMI Across Treatment and Follow-Up | BMI calculated as weight in kg / height in meters squared | Pre-Treatment through Follow-Up (Month 6) | 
| Change in Percent Body Fat Across Treatment and Follow-Up | Body fat percentage (to the nearest 0.1%) will be measured using a Tanita Dual Frequency Total Body Composition Analyzer that assesses weight and bioelectrical impedance for adiposity. | Pre-Treatment through Follow-Up (Month 6) | 
| Eating Disorder Examination Questionnaire (EDE-Q) Scores over Time | The EDE-Q is a 28-item questionnaire measuring eating pathology and is derived directly from the Eating Disorder Examination Interview. The EDE-Q focuses on the past 28 days to assess the main behavioral (eating and purging) and attitudinal features of eating disorders. The 28 items are rated by the participant on a 7-point scale (ranging from 0 to 6), with higher scores indicating increased pathology. The EDE-Q includes 4 subscales: Restraint, Eating Concern, Weight Concern, and Shape Concern. The global score is the average of all 28 items, with a range of 0 to 6. | Pre-Treatment through Follow-Up (Month 6) | 
| PHQ-9 Scores Over Time | The Patient Health Questionnaire (PHQ-9) has 9 items with each rated from 0 to 3. Overall scores ranges from 0 to 27 with 1-4 being minimal depression, 5-9 being mild depression, 10-14 being moderate depression, 15-19 being moderately severe depression and 20-27 being severe depression. | Pre-Treatment through Follow-Up (Month 6) | 
| GAD-7 Scores Over Time | Anxiety symptoms as measured by the Generalized Anxiety Disorder (GAD-7) 7-item scale. The range of the measure is 0 to 21, with higher scores indicating greater anxiety symptoms. | Pre-Treatment through Follow-Up (Month 6) | 
| PROMIS-GI Scores Over Time | Self-reported outcome of GI symptom burden measured using the Patient-Reported Outcomes Measurement Information System (PROMIS) gastro-intestinal (GI) Symptoms scale on the study iPad. The scale includes 4 items and responses to each item are on a 1 (Never) to 5 (Almost Always) scale. Higher scores indicate greater GI symptom burden. | Pre-Treatment through Follow-Up (Month 6) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Fecal Microbiota Transplantation