Fecal Microbiota Transplantation (FMT) in Treatment of Severe and Enduring Anorexia Nervosa
Primary Purpose
Anorexia Nervosa
Status
Withdrawn
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Fecal Microbiota Transplantation (FMT)
Sponsored by
About this trial
This is an interventional other trial for Anorexia Nervosa focused on measuring Fecal Microbiota Transplantation
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
Sites / Locations
- UNC Chapel Hill
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
FMT for SE-AN
Arm Description
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.
Outcomes
Primary Outcome Measures
Proportion of Participants with Adverse Events (AEs)
Safety 1
Proportion of Participants with a Severe Adverse Event (SAE)
Safety 2
Number of Participants Recruited
Feasibility 1, Ability to Recruit 10 Participants with SE-AN
Number of Participants Able to Complete 4 FMT Administrations
Tolerability 1
Number of Participants Reporting Acceptable Levels of GI distress Post FMT
Tolerability 2
Secondary Outcome Measures
Change in BMI Across Treatment and Follow-Up
BMI calculated as weight in kg / height in meters squared
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.
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.
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.
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.
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.
Full Information
NCT ID
NCT03928808
First Posted
April 23, 2019
Last Updated
January 26, 2023
Sponsor
University of North Carolina, Chapel Hill
Collaborators
OpenBiome, Foundation of Hope, North Carolina
1. Study Identification
Unique Protocol Identification Number
NCT03928808
Brief Title
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
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Withdrawn
Why Stopped
Withdrawn due to covid-19 protocols on inpatient eating disorders unit.
Study Start Date
April 1, 2023 (Anticipated)
Primary Completion Date
March 2024 (Anticipated)
Study Completion Date
September 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of North Carolina, Chapel Hill
Collaborators
OpenBiome, Foundation of Hope, North Carolina
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anorexia Nervosa
Keywords
Fecal Microbiota Transplantation
7. Study Design
Primary Purpose
Other
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Model Description
Open Label Pilot Study
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
FMT for SE-AN
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Fecal Microbiota Transplantation (FMT)
Other Intervention Name(s)
OpenBiome FMT Upper Delivery formulation, FMP30
Intervention Description
Nasogastric administration of OpenBiome 25 g/mL solution administered nasogastrically once weekly for 4 consecutive weeks
Primary Outcome Measure Information:
Title
Proportion of Participants with Adverse Events (AEs)
Description
Safety 1
Time Frame
Through day 30 (±3 days)
Title
Proportion of Participants with a Severe Adverse Event (SAE)
Description
Safety 2
Time Frame
Through day 30 (±3 days)
Title
Number of Participants Recruited
Description
Feasibility 1, Ability to Recruit 10 Participants with SE-AN
Time Frame
3 years
Title
Number of Participants Able to Complete 4 FMT Administrations
Description
Tolerability 1
Time Frame
3 years
Title
Number of Participants Reporting Acceptable Levels of GI distress Post FMT
Description
Tolerability 2
Time Frame
Through Week 4
Secondary Outcome Measure Information:
Title
Change in BMI Across Treatment and Follow-Up
Description
BMI calculated as weight in kg / height in meters squared
Time Frame
Pre-Treatment through Follow-Up (Month 6)
Title
Change in Percent Body Fat Across Treatment and Follow-Up
Description
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.
Time Frame
Pre-Treatment through Follow-Up (Month 6)
Title
Eating Disorder Examination Questionnaire (EDE-Q) Scores over Time
Description
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.
Time Frame
Pre-Treatment through Follow-Up (Month 6)
Title
PHQ-9 Scores Over Time
Description
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.
Time Frame
Pre-Treatment through Follow-Up (Month 6)
Title
GAD-7 Scores Over Time
Description
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.
Time Frame
Pre-Treatment through Follow-Up (Month 6)
Title
PROMIS-GI Scores Over Time
Description
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.
Time Frame
Pre-Treatment through Follow-Up (Month 6)
Other Pre-specified Outcome Measures:
Title
FMT Transfer Efficiency
Description
The investigators will establish which particular taxa of bacteria from the FMT material successfully engrafted into the recipient's intestinal tract. FMT transfer efficiency is the percentage of bacterial taxa that successfully transfer from the donor FMT to the FMT recipient's stool.
Time Frame
Pre-Treatment through Follow-Up (Month 6)
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mary Kimmel, MD
Organizational Affiliation
University of North Carolina, Chapel Hill
Official's Role
Principal Investigator
Facility Information:
Facility Name
UNC Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Deidentified individual participant data (IPD) will be made available by controlled access. Qualified researchers with documented evidence of ethical approval and a clear research and statistical analysis plan will be given access through a secure file transfer protocol (FTP) site. Data to be shared include diagnostic information, age, non-identifying demographic data (including BMI and other anthropometric measures), psychometric, and sequence data along with a data dictionary.
IPD Sharing Time Frame
6 months after publication of the primary publication
IPD Sharing Access Criteria
To qualified applicants with documented IRB approval and analytic plan. A Data Use Agreement must be executed with UNC prior to actual sharing of data.
Links:
URL
https://www.openbiome.org/treatment-information/
Description
Details about OpenBiome's different fecal microbiota transplantation formulations. This study will use the FMT Upper Delivery method (FMP30).
Learn more about this trial
Fecal Microbiota Transplantation (FMT) in Treatment of Severe and Enduring Anorexia Nervosa
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