Efficacy of Fecal Microbial Transplantation Treatment in Adults With Atopic Dermatitis

Phase 3

• Conditions: Atopic Dermatitis
• Interventions: Biological: Fecal Microbial Transplantation; Biological: placebo fecal transplantation

• Registration Number: NCT04283968
• Lead Sponsor: Tel-Aviv Sourasky Medical Center

Brief Summary

Prospective double-blinded placebo-controlled study, among adult patients suffering from moderate-to-severe atopic dermatitis (AD), insufficiently responsive to topical and systemic treatment. In the first group all patients will receive 4 fecal microbial transplantations (FMTs) from healthy donors each 2 weeks apart. In the second group all patients will receive 4 placebo transplantations each 2 weeks apart. Patients will be allowed to continue with their baseline medical topical treatment, including moisturizers and glucocorticoids, during the study period, but no new therapy should be commenced. The patients of the second group, who received the placebo treatment will have the possibility to enter an open label phase in which they will receive 4 fecal microbial transplantations (FMTs) from healthy donors each 2 weeks apart. The severity of AD and the fecal microbiome profile will be evaluated by the Scoring Atopic Dermatitis Score (SCORAD score), Investigator Global Assessment scale for Atopic Dermatitis (IGA) and the weekly use of topical corticosteroids, at the beginning of the study, before every FMT, and 1-6 months after the last FMT.

Detailed Description

This is a prospective, double-blinded, placebo-controlled study aimed to assess the safety and clinical efficacy of FMT for the treatment of mild-moderate AD, and to assess the change in the fecal microbiota following FMT in the study population. The study will include 2 groups. In the first group all patients will receive 4 fecal microbial transplantations (FMTs) from healthy donors each 2 weeks apart. In the second group all patients will receive 4 placebo transplantations each 2 weeks apart. Patients will be allowed to continue with their baseline medical topical treatment, including moisturizers and glucocorticoids, during the study period, but no new therapy should be commenced. The patients of the second group, who received the placebo treatment, will have the possibility to enter an open label phase in which they will receive 4 fecal microbial transplantations (FMTs) from healthy donors each 2 weeks apart. The clinical activity of AD, adverse events and the fecal microbiome profile will be evaluated at the beginning of the study, before every FMT, and 1-6 months after the last FMT, using the SCORAD score, the IGA assessment scale, and the weekly use of topical corticosteroids.

During the study period, patients will be allowed to use only topical therapy including emollients and glucocorticoids or calcineurin inhibitors.

FMT preparation and delivery:

Volunteer donors will be healthy, non-pregnant adults aged 18 to 50 years, with a normal body mass index. They will be excluded for any significant medical history or for any use of antibiotics in the preceding 3 months. Candidates should be eligible according to the Israeli Ministry of Health guidelines which include a physical examination and laboratory screening tests including fecal enteric pathogens, serum antibodies to hepatitis A, B, and C; human immunodeficiency virus; HTLV, and Treponema pallidum as well as celiac, CBC (and additional tests that comply with the guidelines of the Israeli Ministry of Health). Stool will be delivered within minutes post defecation in a clean closed plastic container and will be processed at the Tel Aviv Medical Center stool bank facility to prepare capsulized FMT. Briefly, fecal material will be diluted with normal saline (600ml/100g of fecal material), filtered and concentrated the preparation in a centrifuge. The pellet will be suspended in sterile saline and glycerol (20%) that will be added as a bacterial cryoprotectant. This material will be then pipetted into acid-resistant capsules, which will be closed and then secondarily sealed with additional set of capsules. Capsules will be stored frozen at -80°C. Placebo capsules will have identical visually and contained diluted glycerol only.

Capsulized FMT procedure:

FMT will be administered two doses of 15 FMT capsules on two consecutive days (a total of 30 capsules), at the Bacteriotherapy clinic of the Tel Aviv medical center (TLVMC). On the day of administration, capsules frozen at -80°C will be taken out of the freezer and transported to the clinic on ice. Fifteen capsules will be handed individually to the patient and the patient will ingest the capsules immediately with some water. Patients will be asked to fast overnight prior to capsule intake.

Fecal microbial analysis:

In order to examine whether the clinical effect may be mediated by colonization of new bacterial strains, we developed a robust and sensitive method to calculate pairwise DNA sequence dissimilarity between bacterial strains of the same species across distinct metagenomics samples. Donor stool samples that will be used for FMT capsules and stool samples that will be collected from the patients during the study period will be sequenced into metagenomics reads. Reads that will be mapped will be piled up to obtain per-position variant information for every detected species. Difference in the variant of a particular species at a given position between two samples will be defined as having no intersection between the set of detected alleles in the two samples being compared. The estimated species DNA sequence dissimilarity for a pair of samples is then the number of different positions divided by the total number of positions being compared.

Study Timeline

• Study First Submitted: 2020-02-19
• Study First Submitted QC: 2020-02-21
• Study First Posted: 2020-02-25
• Study Start: 2020-10-15
• Status Verified: 2022-07
• Last Update Submitted: 2022-07-21
• Last Update Posted: 2022-07-22
• Primary Completion: 2023-06-01
• Study Completion: 2024-06-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

• Patients who are ≥18 years of age, with moderate-to-severe atopic dermatitis, as defined by a Scoring Atopic Dermatitis Score (SCORAD) score ≥25, with disease duration minimum of 3 years that was inadequately controlled by topical and systemic therapy

Exclusion Criteria

1. Age under 18 years
2. Pregnancy
3. Another concomitant active dermatologic disease.
4. Receiving systemic therapy including phototherapy within 4 weeks before the beginning of the study.
5. receiving any antibiotic or probiotic treatment within 2 weeks before the beginning of the study or during the study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment arm	Fecal Microbial Transplantation	All patients will receive 4 fecal microbial transplantations from healthy donors each 2 weeks apart
Placebo followed by treatment arm	Fecal Microbial Transplantation	All patients will receive 4 placebo fecal transplantations followed by 4 fecal microbial transplantations from healthy donors each 2 weeks apart
Placebo followed by treatment arm	placebo fecal transplantation	All patients will receive 4 placebo fecal transplantations followed by 4 fecal microbial transplantations from healthy donors each 2 weeks apart

Primary Outcome Measures

Name	Time	Method
Assessment of the change in the severity of Atopic Dermatitis after treatment with Fecal Microbial Transplantation	2 weeks after each FMT, and 8 weeks or more after the last FMT	Overall mean change from baseline of the Scoring atopic dermatitis score (SCORAD), described and validated by the European Task Force on Atopic Dermatitis, used for the assessment of the severity of Atopic Dermatitis. The minimal SCORAD score, describing a situation without any signs of atopic dermatitis is 0, the disease is not visible, while the maximal score, describing the most severe presentation of atopic dermatitis, is 103.

Secondary Outcome Measures

Name	Time	Method
Association between the improvement in disease severity and the degree of bacterial strain transmission from donor to patient.	2 weeks after each FMT, and 8 weeks or more after the last FMT	Assessment of the relation between the microbiome of donors and patients by calculating DNA sequence dissimilarity between bacterial strains of the same species across donor stool samples that were used for FMT capsules and stool samples that were collected from the patients during the study period.

Trial Locations

Locations (2)

Department of Dermatology, Tel Aviv Sourasky medical center; 🇮🇱 Tel Aviv, Israel

Dep. of Gastroenterology, Tel Aviv Sourasky Medical Center; 🇮🇱 Tel Aviv, Israel