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

NCT04238091 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: AAAS4183
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Alopecia Areata; Alopecia Totalis; Alopecia Universalis

Keywords

Hair Loss; Alopecia

Outcome Measures

Primary Outcomes (4)

• Number of responders in patients treated with FMT

  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.

  24 weeks 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 a serious adverse event (SAE) 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 Outcomes (6)

• Time of relapse in responders

  24 weeks post-treatment

• 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

• 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

Study Arms (2)

Antibiotics prior to FMT

ACTIVE COMPARATOR

Participants will take a standardized regimen of antibiotics for three days prior to fecal transplant.

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

No Antibiotics prior to FMT

ACTIVE COMPARATOR

Participants will not take antibiotics before the transplant.

Drug: Fecal material transfer therapy; Procedure: 4mm Punch Biopsy of Scalp; Diagnostic Test: Blood draw; Procedure: Skin Microbiome sampling; Procedure: Hair Microbiome Sampling; Drug: Bowel Prep

Interventions

Fecal material transfer therapy DRUG

Fecal microbiota transplants will be performed as follows: FMP Retention Enema: (FMP 250 mL) Dosage Form: Screened human donor stool, suspended in diluent of 12.5% glycerol and sterile normal saline buffer (0.9% NaCl) standardized to a 5X concentration (1g stool : 5mL diluent ratio), homogenized, filtered to 330 microns and aliquoted to sterile 250mL vessels. Route of Administration: Fecal transplant will be performed under medical supervision. Lubricated enema tube will be inserted into rectum and contents expelled into the distal colon with the subject requested to retain material for a target dwell time of 3 to 24 hours with a mean target of 10 hours. Participants will lie in the left lateral decubitus position but if mobility permits will rotate to supine and right lateral decubitus position. One half of study subjects will receive a 3 day course of antibiotics prior to fecal transplant, while the other half will not.

Also known as: FMT

Antibiotics prior to FMT; No Antibiotics prior to FMT

4mm Punch Biopsy of Scalp PROCEDURE

For the skin biopsy, the doctor will select an appropriate area on the scalp (or skin) as the biopsy site. The area will then be numbed (anesthetized). The study doctor or his/hers designee will then use a cylindrical instrument with a sharp edge (similar to a small cookie-cutter) to remove a 4mm cylinder of skin (smaller than the size of a pencil eraser). After the skin is removed, the biopsy site will be closed with absorbable stitches when appropriate. Approximately 2 to 4 stitches may be placed at the wound site to improve healing. Multiple skin punch biopsies may be taken throughout the entire length of the study

Also known as: Punch Biopsy of Scalp

Antibiotics prior to FMT; No Antibiotics prior to FMT

Blood draw DIAGNOSTIC_TEST

Blood will be collected by a standard venipuncture procedure. 60-80cc of blood will be drawn from a patient per blood draw occurrence. Blood samples will be transferred to the research facility. Samples will be used to either stained with cell surface antibodies for fluorescence acquisition cell sorting (FACS) analysis (FACS experiments will allow for assessment of the subset and activation status of immune cells involved in AA or other cutaneous disorder pathology) or to extract DNA for the purposes of exome or genomic sequencing or genotyping of disease associated genes

Antibiotics prior to FMT; No Antibiotics prior to FMT

Skin Microbiome sampling PROCEDURE

Skin microbiome will be collected using skin swabs at the time of recruitment according to established protocols outlined by the Human Microbiome Project. Sterile (germ-free) techniques will be used for collection of all specimens, with careful avoidance of contamination of collection area by gloved hands. The sites that will be sampled are (in sequence): Lesional AA skin, non-lesional scalp skin, retro-auricular crease, ante-cubital fossa, and anterior nares. Skin surface specimens will be collected with a Catch-All Sample Collection Swab swab that looks similar to a q-tip and is, moistened with sterile solution. Skin will be swabbed approximately 50 times along the scalp, behind your ear and on your arm, and twisted 2 times around the front of the nose.

Antibiotics prior to FMT; No Antibiotics prior to FMT

Hair Microbiome Sampling PROCEDURE

Hair follicle microbiome (bacteria that live in the hair follicle) will be collected as follows: several hairs will be plucked from the scalp at a time using tweezers, once plucked the bulbs of the hairs will be cut using sterile surgical scissors and processed. Approximately 10-15 hairs will be plucked for processing. The number of hairs plucked may be increased depending on the number of hairs containing bulbs. Up to 50 hairs may be plucked, as long as the subject is able to tolerate it. Only several hairs will be plucked at a time in order to minimize pain and discomfort of the procedure.

Antibiotics prior to FMT; No Antibiotics prior to FMT

Pre-FMT Antibiotic Cocktail DRUG

For three days prior to the transplant, one half (20) of the subjects enrolled will be treated with antibiotics to reduce the burden of the existing microbiome. The antibiotic regimen will consist of: oral vancomycin 250 mg qid, ciprofloxacin 500 mg bid, and metronidazole 500 mg tid. For subjects who have antibiotic allergies, appropriate antibiotic substitutions will be made. Subjects will stop the antibiotics 48 hours before the fecal transplant.

Antibiotics prior to FMT

Bowel Prep DRUG

The night before the transplant, all enrolled subjects will take 20 mg of bisacodyl and a large volume bowel preparation (GoLyteley 4000cc). Fecal transplant will be performed under medical supervision. After the transplant, subjects will take 4 mg of loperamide to increase transplant retention.

Antibiotics prior to FMT; No Antibiotics prior to FMT

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Lindsey Bordone: lead

Related Publications (2)

• Xie WR, Yang XY, Xia HH, Wu LH, He XX. Hair regrowth following fecal microbiota transplantation in an elderly patient with alopecia areata: A case report and review of the literature. World J Clin Cases. 2019 Oct 6;7(19):3074-3081. doi: 10.12998/wjcc.v7.i19.3074.

  PMID: 31624757 BACKGROUND

• Rebello D, Wang E, Yen E, Lio PA, Kelly CR. Hair Growth in Two Alopecia Patients after Fecal Microbiota Transplant. ACG Case Rep J. 2017 Sep 13;4:e107. doi: 10.14309/crj.2017.107. eCollection 2017.

  PMID: 28932754 BACKGROUND

MeSH Terms

Conditions

Alopecia Areata; Alopecia universalis; Alopecia

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Hypotrichosis; Hair Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Lindsey Bordone, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Dermatology

Study Record Dates

• First Submitted: January 14, 2020
• First Posted: January 23, 2020
• Study Start: December 19, 2019
• Primary Completion: March 2, 2022
• Study Completion: March 2, 2022
• Last Updated: March 21, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share