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

Primary Purpose

Alopecia Areata, Alopecia Totalis, Alopecia Universalis

Status

Withdrawn

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

Fecal material transfer therapy

4mm Punch Biopsy of Scalp

Blood draw

Skin Microbiome sampling

Hair Microbiome Sampling

Pre-FMT Antibiotic Cocktail

Bowel Prep

About this trial

This is an interventional treatment trial for Alopecia Areata focused on measuring Hair Loss, Alopecia

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Antibiotics prior to FMT

No Antibiotics prior to FMT

Arm Description

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

Participants will not take antibiotics before the transplant.

Outcomes

Primary Outcome Measures

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.

Proportion of participants with an adverse event (AE) through day 30 (±3 days) after FMT

Proportion of participants with a serious adverse event (SAE) through day 30 (±3 days) after FMT

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

Secondary Outcome Measures

Time of relapse in responders

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

Proportion of participants with an SAE through week 4 (±5 days) after FMT

Proportion of participants with a SAE at month 6 (±14 days) after randomization

Proportion of participants with a SAE at month 12 (±14 days) after randomization

Percent hair regrowth from baseline

This will be determined by SALT measurements.

Full Information

NCT ID

NCT04238091

First Posted

January 14, 2020

Last Updated

March 4, 2022

Sponsor

Lindsey Bordone

1. Study Identification

Unique Protocol Identification Number

NCT04238091

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2022

Overall Recruitment Status

Withdrawn

Why Stopped

Investigator is no longer interested in moving forward with this study

Study Start Date

December 19, 2019 (Actual)

Primary Completion Date

March 2, 2022 (Actual)

Study Completion Date

March 2, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Lindsey Bordone

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Alopecia Areata, Alopecia Totalis, Alopecia Universalis

Keywords

Hair Loss, Alopecia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Antibiotics prior to FMT

Arm Type

Active Comparator

Arm Description

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

Arm Title

No Antibiotics prior to FMT

Arm Type

Active Comparator

Arm Description

Participants will not take antibiotics before the transplant.

Intervention Type

Drug

Intervention Name(s)

Fecal material transfer therapy

Other Intervention Name(s)

FMT

Intervention Description

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.

Intervention Type

Procedure

Intervention Name(s)

4mm Punch Biopsy of Scalp

Other Intervention Name(s)

Punch Biopsy of Scalp

Intervention Description

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

Intervention Type

Diagnostic Test

Intervention Name(s)

Blood draw

Intervention Description

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

Intervention Type

Procedure

Intervention Name(s)

Skin Microbiome sampling

Intervention Description

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.

Intervention Type

Procedure

Intervention Name(s)

Hair Microbiome Sampling

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Pre-FMT Antibiotic Cocktail

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Bowel Prep

Intervention Description

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.

Primary Outcome Measure Information:

Title

Number of responders in patients treated with FMT

Description

Time Frame

24 weeks post-treatment

Title

Proportion of participants with an adverse event (AE) through day 30 (±3 days) after FMT

Time Frame

30 days post-treatment

Title

Proportion of participants with a serious adverse event (SAE) through day 30 (±3 days) after FMT

Time Frame

30 days post-treatment

Title

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

Time Frame

30 days post-treatment

Secondary Outcome Measure Information:

Title

Time of relapse in responders

Description

The timing of relapse in responders will be followed for 6 months post therapy.

Time Frame

24 weeks post-treatment

Title

Proportion of participants with an AE through week 4 (±5 days) after FMT

Time Frame

4 weeks post-treatment

Title

Proportion of participants with an SAE through week 4 (±5 days) after FMT

Time Frame

4 weeks post-treatment

Title

Proportion of participants with a SAE at month 6 (±14 days) after randomization

Time Frame

6 months post-randomization

Title

Proportion of participants with a SAE at month 12 (±14 days) after randomization

Time Frame

12 months post-randomization

Title

Percent hair regrowth from baseline

Description

This will be determined by SALT measurements.

Time Frame

24 weeks post-treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Lindsey Bordone, MD

Organizational Affiliation

Columbia University

Official's Role

Principal Investigator

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

31624757

Citation

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.

Results Reference

background

PubMed Identifier

28932754

Citation

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.

Results Reference

background

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

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