Safety and Feasibility of FMT for Immune Recovery After HSCT

NCT07755319 | Not Yet Recruiting Phase 1

• 1 other identifier: SOOCHOW-WXJ-2026699
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 1

Brief Summary

Patients who undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT) often experience slow and incomplete recovery of their immune system, particularly the part responsible for producing antibodies (humoral immunity). This can lead to increased risk of infections and other complications. Previous studies suggest that the gut microbiome and its metabolites, such as short-chain fatty acids (propionate and butyrate), play a critical role in immune recovery. This study has two phases. In the first phase, we will observe changes in immune function, lymphocyte subsets, and gut metabolites (propionate and butyrate) before and at 1, 3, and 6 months after transplantation in 50-80 patients. We will compare patients with severe immune deficiency to those with normal recovery to identify differences in gut bacteria and metabolites. In the second phase, we will perform selective fecal microbiota transplantation (FMT) in 6 patients who still have severe humoral immunodeficiency at 6 months post-transplant. The FMT capsules will be specially selected from donors whose gut bacteria are rich in both propionate-producing and butyrate-producing strains. Patients will receive 20 capsules daily for 3 consecutive days (60 capsules total). We will evaluate the safety and feasibility of this approach, and observe whether fecal secretory immunoglobulin A (sIgA) shows signs of recovery at 3 months after FMT. The study is expected to take approximately 2 years to complete. Findings may provide a new precision microbiome-based strategy to promote immune recovery after transplantation.

Conditions

Humoral Immunodeficiency; Hematopoietic Stem Cell Transplantation

Outcome Measures

Primary Outcomes (1)

• Composite Endpoint of Safety and Feasibility of Selective FMT in Post-Allo-HSCT Patients

  Safety is assessed by the incidence, severity (CTCAE v5.0), and attribution of treatment-emergent adverse events (TEAEs) within 3 months post-FMT, with particular monitoring for grade ≥3 AEs, serious adverse events (SAEs), and FMT-related exacerbation of GVHD or bacteremia. Feasibility is measured by the FMT completion rate, defined as the proportion of enrolled patients who successfully receive ≥90% of the planned total dose (≥54 of 60 oral capsules). The study will be considered to have demonstrated safety and feasibility if: (a) the completion rate is ≥80% (lower bound of 95% CI \>60%); (b) the incidence of FMT-related grade ≥3 AEs is ≤15% (upper bound of 95% CI \<30%); and (c) no FMT-related SAEs occur that are definitely or probably attributed to the intervention. Independent safety review will be performed after every 5 patients, with predefined stopping rules.

  3 months post-FMT

Secondary Outcomes (5)

• Change in Fecal Secretory Immunoglobulin A (sIgA) Concentration

  Baseline to 3 months post-FMT

• Change in Serum Immunoglobulin Levels

  Baseline to 3 months post-FMT

• Change in Fecal Short-Chain Fatty Acid Concentrations

  Baseline to 2 weeks post-FMT

• Change in Peripheral Blood B-Cell Subsets

  Baseline to 3 months post-FMT

• Donor Microbiota Engraftment Rate

  3 months post-FMT

Study Arms (1)

FMT Treatment Group

EXPERIMENTAL

Oral administration of human-derived gut microbiota capsules, each containing no fewer than 2×10¹¹ organisms, given at a dose of 20 capsules per day for 3 consecutive days (total 60 capsules per course).

Biological: Fecal microbiota transplantation (FMT)

Interventions

Fecal microbiota transplantation (FMT) BIOLOGICAL

The FMT capsules are prepared from healthy donor feces screened according to international consensus guidelines. Oral administration of human-derived gut microbiota capsules, each containing no fewer than 2×10¹¹ organisms, given at a dose of 20 capsules per day for 3 consecutive days (total 60 capsules per course).No dose adjustments will be made during the study. The total treatment duration is 3 days. This is a single-arm, open-label, phase I/IIa proof-of-concept safety exploratory trial. Participants will be followed for 3 months post-FMT to assess safety, feasibility, and preliminary biological signals of immune recovery.

FMT Treatment Group

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years
• Receiving first allogeneic hematopoietic stem cell transplantation (allo-HSCT) with myeloablative or reduced-intensity conditioning
• Able to complete scheduled follow-up visits and sample collections
• Willing and able to provide written informed consent
• For Phase 2 (FMT intervention): participants must additionally meet all of the following criteria at 6 months post-transplant:
• Serum IgA \< 0.07 g/L with IgG and IgM not yet recovered to normal range
• No active grade III-IV acute graft-versus-host disease (GVHD)
• Off systemic antibiotics for at least 2 weeks
• Willing to receive fecal microbiota transplantation (FMT) and sign dedicated informed consent for the intervention

You may not qualify if:

• Early post-transplant death or loss to follow-up
• Active grade III-IV acute GVHD (at time of screening)
• Continuous use of high-dose immunosuppressants (prednisone-equivalent dose \> 1 mg/kg/day)
• Refusal to participate or inability to comply with study procedures
• For Phase 2 (FMT intervention): participants meeting any of the following criteria will be excluded from the FMT phase:
• Gastrointestinal obstruction, perforation, or severe intestinal dysfunction
• Severe cardiac, hepatic, or renal insufficiency that would preclude safe FMT administration
• Known allergy or hypersensitivity to any component of the FMT preparation

Sponsors & Collaborators

• The First Affiliated Hospital of Soochow University: lead

Study Sites (1)

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, 215006, China

Location

Related Publications (3)

• Shin JH, Tillotson G, MacKenzie TN, Warren CA, Wexler HM, Goldstein EJC. Bacteroides and related species: The keystone taxa of the human gut microbiota. Anaerobe. 2024 Feb;85:102819. doi: 10.1016/j.anaerobe.2024.102819. Epub 2024 Jan 10.

  PMID: 38215933 RESULT

• Qu S, Gao Y, Ma J, Yan Q. Microbiota-derived short-chain fatty acids functions in the biology of B lymphocytes: From differentiation to antibody formation. Biomed Pharmacother. 2023 Oct 27;168:115773. doi: 10.1016/j.biopha.2023.115773. Online ahead of print.

  PMID: 39491858 RESULT

• Goguyer-Deschaumes R, Waeckel L, Killian M, Rochereau N, Paul S. Metabolites and secretory immunoglobulins: messengers and effectors of the host-microbiota intestinal equilibrium. Trends Immunol. 2022 Jan;43(1):63-77. doi: 10.1016/j.it.2021.11.005. Epub 2021 Nov 27.

  PMID: 34848167 RESULT

MeSH Terms

Interventions

Fecal Microbiota Transplantation

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Central Study Contacts

xiaojin Wu, M.D., Ph.D.

CONTACT

+86-051267976360; wuxiaojin@suda.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2026
• First Posted: August 10, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): October 31, 2028
• Study Completion (Estimated): October 31, 2028
• Last Updated: August 10, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: De-identified IPD and supporting documents will be available starting 6 months after publication of the primary study results and will remain accessible for 5 years thereafter, in accordance with the data retention policy of the participating institution and funding agency requirements.
• Access Criteria: Access will be granted to qualified academic and non-commercial researchers who submit a methodologically sound research proposal with scientific merit. Requesters will have access to de-identified individual participant data (including 16S sequencing, SCFA concentrations, serum Ig, fecal sIgA, TBNK subsets, and clinical outcomes), study protocol, SAP, ICF, CSR, and analytic code. Data will be provided via a secure data-sharing platform after execution of a data access agreement and approval by the Institutional Review Board of the participating institution. Raw sequencing data will be publicly accessible through NCBI SRA, and metabolomics data through MetaboLights, with accession numbers provided in the publication. Requests should be directed to the Principal Investigator at the institutional email address. Data use is restricted to the approved research purpose, and re-identification or redistribution is prohibited.

Locations

CN (1)