Feasibility Study of Using Fecal Microbiota Transplants in Anorexia Nervosa

Study Overview
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Brief Summary
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The investigators hypothesize that prolonged undernutrition in anorexia nervosa alters the microbiome to a different steady-state (dysbiotic) composition that sustains the disease, even after returning to normal diet. The investigators propose that transplanting a fully ecologically functioning GM from a healthy donor, through a FMT, can reboot the gut-brain-axis, ameliorate symptoms and improve clinical outcomes. To approach this, in the challenging AN patient group, the investigators want to conduct a FMT feasibility/pilot study.

Detailed Description
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Anorexia nervosa (AN) still carries the highest fatality rate of any psychiatric disease, and less than half of the patients recover, completely refractory to any treatment. The etiology remains unknown and evidence for treatment is lacking. We have an established collaboration bridging several disciplines and people in medicine, bioinformatics and biology with a focus on the pathological role of gut microbiome in the psychiatric disorder Anorexia nervosa. The GM in healthy people has been shown to affect weight gain, appetite and behavior through the gut-brain axis. We hypothesize that prolonged undernutrition in AN alters the microbiome to a different steady-state (dysbiotic) composition that sustains the disease, even after returning to normal diet. AN patients enter voluntarily into programs of therapeutic weight gain and reintroduction to normal food intake. The investigators propose that transplanting a fully ecologically functioning GM from a healthy donor, through a FMT, can reboot the gut-brain-axis, ameliorate symptoms and improve clinical outcomes. To approach this, in the challenging AN patient group, we want to conduct a FMT feasibility/pilot study. The investigators want approach the FMT intervention, with 20 AN patients in sequence before any attempt at more complex blinded /placebo clinical trials. The investigators will collect GM samples and clinical data from these patients and describe the altered composition and diversity of the AN-GM and how it changes with FMT. Ultimately, the investigators aim to provide evidence that GM modulation with FMT can ameliorateclinical outcomes of AN. The investigators will investigate the feasibility of using FMT in supportive treatment of AN and by identifying specific bacterial and viral changes with FMT, we will lay the groundwork for randomized placebo-controlledstudies, to develop new GM interventions to complement current treatment of AN.

Official Title
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Feasibility Study of Using Fecal Microbiota Transplants (FMT) in Supportive Treatment of Anorexia Nervosa

Conditions
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Anorexia Nervosa, Microbiome Dysbiosis

Intervention / Treatment
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* Biological: Fecal Microbiome Transplant


Participation Criteria
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Eligibility Criteria
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Inclusion: Women referred to the participating specialized centers or by advertising who fulfill the of a diagnosis of Anorexia Nervosa according to the criteria as specified in the Diagnostic and Statistical Manual of Mental Disorders(DSM) version 5. Exclusion: Age <18 years. Known ongoing abuse of laxatives. Antibiotic treatment within the last three months. Probiotics within the last month Inflammatory bowel disease, colorectal cancer or other known chronic bowel disorder

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Interventional Model Description: 1 single FMT event either oral route or rectal. Sampling fecal matter and blood at baseline and 1 week after FMT.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FMT<br>rectal or oral route FMT | Biological: Fecal Microbiome Transplant<br>* Fecal matter from healthy age/sex matched established and screened donors, recruited from the Danish Blood-donor system<br>* Other names: Fecal Matter Transplant;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of FMT in AN patients | The recruitment and compliance of 10-20 patients/year is feasible | 2 years | 
| Preferred route of FMT (questionnaire) | FMT is offered as a Capsule-treatment orally or as an enema-rectally | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A single FMT treatment can alter GM composition in AN patients short term | 16S rRNA gene sequencing: Outcome: we expect GM to normalize towards the donor GM composition e.g higher diversity and composition of species, within the single patient and also compared to both healthy(NO-FMT) and AN(NO-FMT) controls. | 2 yrs | 
| A single FMT treatment can alter gut brain signaling in serum. might changes serum signal molecules related to appetite and metabolism with in same patien | measuring appetite related biomarkers: PYY might changes serum signal molecules related to appetite and metabolism with in same patient comparison, before and 1 week after FMT in a direction for higher appetite | 2 yrs | 
| A single FMT treatment can alter gut brain signaling in serum. might changes serum signal molecules related to appetite and metabolism with in same patien | measuring appetite related biomarkers: Leptin might changes serum signal molecules related to appetite and metabolism with in same patient comparison, before and 1 week after FMT in a direction for higher appetite | 2 yrs | 
| A single FMT treatment can alter gut brain signaling in serum. might changes serum signal molecules related to appetite and metabolism with in same patien | measuring appetite related biomarkers: Ghrelin, | 2 yrs | 
| A single FMT treatment can alter gut brain signaling in serum. might changes serum signal molecules related to appetite and metabolism with in same patien | measuring appetite related biomarkers: Insulin | 2 yrs | 
| A single FMT treatment can alter gut brain signaling in serum. might changes serum signal molecules related to appetite and metabolism with in same patien | measuring appetite related biomarkers: Glucagon | 2 yrs | 
| A single FMT treatment can alter gut brain signaling in serum. might changes serum signal molecules related to appetite and metabolism with in same patien | measuring appetite related biomarkers: GLP-1 | 2 yrs |