Clinical Trial to Evaluate the Efficacy of Fecal Microbiota Transplantation in Patients With Alopecia Areata

Phase 2

Withdrawn

• Conditions: Alopecia Areata; Alopecia Universalis; Alopecia Totalis
• Interventions: Drug: Fecal material transfer therapy; Procedure: 4mm Punch Biopsy of Scalp; Diagnostic Test: Blood draw; Procedure: Skin Microbiome sampling; Procedure: Hair Microbiome Sampling; Drug: Pre-FMT Antibiotic Cocktail; Drug: Bowel Prep

• Registration Number: NCT04238091
• Lead Sponsor: Lindsey Bordone

Brief Summary

The purpose of this study is to examine fecal transfer as a potential treatment for Alopecia Areata (AA). This trial will attempt to discover if fecal transfer can treat immune-related hair loss.

Detailed Description

Alopecia areata (AA) is an autoimmune condition resulting in chronic and relapsing hair loss. AA patchy is associated with well-circumscribed patches of hair loss, commonly on the scalp or face, while alopecia totalis (AT) and alopecia universalis (AU) are two severe types of AA characterized by 95% or more hair loss on the scalp (AT) or body (AU). Although the exact underlying mechanisms that cause AA are unknown, T lymphocyte cells are implicated, as they release pro-inflammatory cytokines and chemokines around the hair follicles, triggering a cascade and ultimately resulting in hair loss.

Fecal microbiota transfer (FMT) involves the transfer of stool (feces) from a healthy donor to an AA recipient. Research suggests that changing the type of bacteria in an individual's intestine may carry the potential to alter (increase or decrease) the recipient's potential for certain conditions, even autoimmune conditions.

Study Timeline

• Study Start: 2019-12-19
• Study First Submitted: 2020-01-14
• Study First Submitted QC: 2020-01-21
• Study First Posted: 2020-01-23
• Status Verified: 2022-03
• Primary Completion: 2022-03-02
• Study Completion: 2022-03-02
• Last Update Submitted: 2022-03-04
• Last Update Posted: 2022-03-21

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

• Patients 18 to 75 years of age with moderate to severe alopecia areata (SALT score >30%)
• Patients with a diagnosis of patch type alopecia areata, totalis, or universalis.
• Duration of hair loss greater than 3 months.
• No evidence of active, ongoing regrowth present at baseline.
• Females of childbearing potential must have a negative urine or serum pregnancy test at screening and immediately prior to FMT on the day of FMT, and
• Females of childbearing potential must agree to use an effective form of contraception from 14 days prior to study antibiotics through at least 30 days after FMT. Acceptable forms of contraception include Oral/intramuscular (IM) contraceptives, intrauterine device (IUD), surgical sterilization.

Exclusion Criteria

• Inability (e.g. dysphagia) to or unwilling to swallow capsules
• Active gastrointestinal infection at time of enrollment
• 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 treatment.
• Requires continued antibiotic use or anticipates antibiotic use in the upcoming 4 weeks
• Known or suspected toxic megacolon and/or known small bowel ileus
• Major gastrointestinal surgery (e.g. significant bowel resection) within 3 months before enrollment. This does not include appendectomy or cholecystectomy
• History of total colectomy or bariatric surgery
• Concurrent intensive induction chemotherapy, radiation therapy or biological treatment for active malignancy
• Unable or unwilling to comply with protocol requirements
• Expected life expectancy < 6 months
• Previous FMT or microbiome-based products at any time excluding this study
• Patients with a history of severe anaphylactic or anaphylactoid food allergy
• Solid organ transplant recipients 90 days post-transplant or on active treatment for rejection
• If at risk for CMV/EBV associated disease (at investigator's discretion, e.g. immunocompromised), negative immunoglobulin G (igG) testing for cytomegalovirus (CMV) or Epstein Barr Virus (EBV).
• 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
• Patients with a history of or existing skin diseases affecting the scalp such as psoriasis or seborrheic dermatitis and patients with evidence of infection or skin cancer in the treated areas
• Patients in whom the diagnosis of alopecia areata is questionable
• Patients in whom regrowth is present/evident at baseline in the areas to be treated
• Patients with active medical conditions or malignancies (except adequately treated basal or squamous cell carcinoma of the skin) which in the opinion of the investigator would increase the risks associated with study participation, including patients with a history of recurrent infections
• Patients known to be HIV or hepatitis B or C positive or otherwise immunocompromised
• Patients unwilling or unable to discontinue treatments known to affect hair regrowth in alopecia areata
• Patients who have been treated with intralesional steroids, systemic steroids, anthralin, squaric acid, diphenylcyclopropenone (DPCP), protopic, minoxidil, Janus kinase (JAK) inhibitors or other medication which in the opinion of the investigator may affect hair regrowth, within one month of the baseline visit.
• Patients determined by the investigator to have extreme diets.
• Patients (children) under the age of 18.
• Pregnant and breastfeeding females.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Antibiotics prior to FMT	Pre-FMT Antibiotic Cocktail	Participants will take a standardized regimen of antibiotics for three days prior to fecal transplant.
Antibiotics prior to FMT	Bowel Prep	Participants will take a standardized regimen of antibiotics for three days prior to fecal transplant.
No Antibiotics prior to FMT	Fecal material transfer therapy	Participants will not take antibiotics before the transplant.
No Antibiotics prior to FMT	Hair Microbiome Sampling	Participants will not take antibiotics before the transplant.
Antibiotics prior to FMT	Fecal material transfer therapy	Participants will take a standardized regimen of antibiotics for three days prior to fecal transplant.
Antibiotics prior to FMT	4mm Punch Biopsy of Scalp	Participants will take a standardized regimen of antibiotics for three days prior to fecal transplant.
Antibiotics prior to FMT	Blood draw	Participants will take a standardized regimen of antibiotics for three days prior to fecal transplant.
Antibiotics prior to FMT	Skin Microbiome sampling	Participants will take a standardized regimen of antibiotics for three days prior to fecal transplant.
Antibiotics prior to FMT	Hair Microbiome Sampling	Participants will take a standardized regimen of antibiotics for three days prior to fecal transplant.
No Antibiotics prior to FMT	Blood draw	Participants will not take antibiotics before the transplant.
No Antibiotics prior to FMT	Bowel Prep	Participants will not take antibiotics before the transplant.
No Antibiotics prior to FMT	4mm Punch Biopsy of Scalp	Participants will not take antibiotics before the transplant.
No Antibiotics prior to FMT	Skin Microbiome sampling	Participants will not take antibiotics before the transplant.

Primary Outcome Measures

Name	Time	Method
Number of responders in patients treated with FMT	24 weeks post-treatment	Responders are defined as subjects achieving 50% or greater (% change, NOT absolute change) hair re-growth from baseline as assessed by SALT (Severity of Alopecia Tool) score where 0 indicates no hair and 100 is a full head of hair (i.e. 50% regrowth at week 24). A higher SALT score/ higher percent change indicate a better outcome.
Proportion of participants with a serious adverse event (SAE) through day 30 (±3 days) after FMT	30 days post-treatment
Proportion of participants with an adverse event (AE) through day 30 (±3 days) after FMT	30 days post-treatment
Proportion of participants with newly acquired transmissible infectious diseases which are considered adverse events of special interest (AESI) through day 30 (±3 days) after FMT	30 days post-treatment

Secondary Outcome Measures

Name	Time	Method
Proportion of participants with a SAE at month 6 (±14 days) after randomization	6 months post-randomization
Proportion of participants with a SAE at month 12 (±14 days) after randomization	12 months post-randomization
Percent hair regrowth from baseline	24 weeks post-treatment	This will be determined by SALT measurements.
Time of relapse in responders	24 weeks post-treatment	The timing of relapse in responders will be followed for 6 months post therapy.
Proportion of participants with an AE through week 4 (±5 days) after FMT	4 weeks post-treatment
Proportion of participants with an SAE through week 4 (±5 days) after FMT	4 weeks post-treatment