Safety and Feasibility of FMT for Immune Recovery After HSCT
Trial statusNot yet recruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorThe First Affiliated Hospital of Soochow University
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
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
Trial design
Design model
Single group
Treatments tested in this trial
Fecal microbiota transplantation (FMT)
Biological/VaccineThe 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.
Treatment groups
86 Participants
are divided into 1 treatment groupGroup A: FMT Treatment GroupExperimental treatment 1 intervention
Trial outcomes
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.
Time frame
3 months post-FMTSecondary outcomes
1
Change in Fecal Secretory Immunoglobulin A (sIgA) Concentration
Fecal sIgA concentration (µg/g feces) will be measured using a commercially available enzyme-linked immunosorbent assay (ELISA) kit specific for human secretory immunoglobulin A. Stool samples will be collected at baseline (pre-FMT) and at 3 months post-FMT. The endpoint is defined as the absolute and percentage change from baseline to 3 months post-FMT, with a signal of immune reconstitution defined as an increase of ≥50% from baseline or normalization to ≥50 µg/g feces. The assay will be performed according to the manufacturer's instructions, and results will be expressed as µg per gram of feces.
Time frame
Baseline to 3 months post-FMT2
Change in Serum Immunoglobulin Levels
Serum IgA, IgM, and IgG concentrations (g/L) will be measured using a commercially available immunoturbidimetric or nephelometric assay on an automated clinical chemistry analyzer. Blood samples will be collected at baseline (pre-FMT) and at 3 months post-FMT. The endpoint is defined as the absolute and percentage change from baseline to 3 months post-FMT. Assays will be performed in the institutional clinical laboratory according to standard operating procedures, and results will be expressed as grams per liter.
Time frame
Baseline to 3 months post-FMT3
Change in Fecal Short-Chain Fatty Acid Concentrations
Fecal propionate and butyrate concentrations (µmol/g feces) will be quantified using gas chromatography-mass spectrometry (GC-MS). Stool samples will be collected at baseline (pre-FMT) and at 2 weeks post-FMT. Briefly, fecal samples will be acidified, extracted with organic solvent, and derivatized prior to GC-MS analysis. The endpoint is defined as the absolute and percentage change from baseline to 2 weeks post-FMT. The assay will be performed according to established laboratory protocols, and results will be expressed as µmol per gram of feces.
Time frame
Baseline to 2 weeks post-FMT4
Change in Peripheral Blood B-Cell Subsets
Peripheral blood B-cell subsets will be characterized by multi-parameter flow cytometry. Whole blood samples will be collected in EDTA tubes at baseline (pre-FMT) and at 3 months post-FMT. The following B-cell subsets will be quantified as percentages of total CD19⁺ B cells: plasmablasts (CD19⁺CD27ʰⁱCD38ʰⁱ), IgA⁺ B cells (CD19⁺IgA⁺), and exhausted B cells (CD19⁺CD21ˡᵒʷCD11c⁺). A minimum of 200,000 events will be acquired per sample using a flow cytometer. Data will be analyzed using FlowJo software. The endpoint is defined as the absolute and percentage change in each subset frequency from baseline to 3 months post-FMT.
Time frame
Baseline to 3 months post-FMTSponsors and contacts
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Source ClinicalTrials.gov
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