Microbiota Transplant With Antibiotic Preconditioning and Fiber Supplementation in PAH.

Phase 1Not Yet RecruitingNCT07751120

University of Minnesota24 enrolled

Overview

This pilot clinical trial analysis will evaluate the initial safety, feasibility, and pharmacokinetics of microbiota transplant therapy (MTT) with antibiotic pre-conditioning and fiber supplementation vs. placebo in patients with pulmonary arterial hypertension (PAH). This trial will inform development of future trials of MTT as a treatment for PAH. 24 PAH patients will be randomized to receive either MTT with antibiotic preconditioning + fiber supplementation, MTT with antibiotic preconditioning + placebo supplementation, or placebo + placebo supplementation. MTT will in a capsule form composed of freeze-dried, encapsulated intestinal microbiota from healthy donors. Fiber supplementation will be 10-14 gm oral fiber supplement. Patients will be followed at week 1, week 2, week 4, week 12, and week 24. Patient will undergo stool sample collection at baseline, week 1, week 4, and week 12, blood sample collection at baseline, week 4, and week,12. In addition, patient will undergo an echocardiogram, six-minute walk test (6MWT) and quality of life questionnaire at baseline and at week 12.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

SUPPORTIVE_CARE

Masking

DOUBLE

Enrollment

Conditions

Pulmonary Arterial Hypertension

Interventions

MTT with antibiotic preconditioning + fiber supplementationDRUG

MTT will in a capsule form composed of freeze-dried, encapsulated intestinal microbiota from healthy donors. Fiber supplementation will be 10-14 gm oral fiber supplement. Patients will be followed at week 1, week 2, week 4, week 12, and week 24. Patient will undergo stool sample collection at baseline, week 1, week 4, and week 12, blood sample collection at baseline, week 4, and week, 12. In addition, patient will undergo an echocardiogram, six-minute walk test (6MWT) and quality of life questionnaire at baseline and at week 12.

MTT with antibiotic preconditioning + placebo supplementationDRUG

MTT will in a capsule form composed of freeze-dried, encapsulated intestinal microbiota from healthy donors. Patients will be followed at week 1, week 2, week 4, week 12, and week 24. Patient will undergo stool sample collection at baseline, week 1, week 4, and week 12, blood sample collection at baseline, week 4, and week, 12. In addition, patient will undergo an echocardiogram, six-minute walk test (6MWT) and quality of life questionnaire at baseline and at week 12.

MTT with placebo + placebo supplementation.DRUG

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Provision of signed and dated consent form * Ages 18-75 * Diagnosis of PAH * On stable treatment for PAH for one month prior to enrollment * Able to swallow capsules * Able to provide blood sample and fecal sample * Stated willingness to comply with all study procedures and availability for the duration of trial to follow-up by telephone, in-person, email, and/or video visits or correspondence. Exclusion Criteria: * Dysphagia to pills * Clinically active inflammatory bowel disease * Pregnancy or breastfeeding. A pregnancy test will be obtained from females of child- bearing potential at the screening visit or day 1 (prior to the receipt of MTT). Patients with a positive pregnancy test will be excluded. A negative result will be required for subjects who are females of child-bearing potential to receive MTT. Patients will be counseled to avoid pregnancy which is the standard of care for patients with PAH. * Life expectancy of \< 6 months * Presence of ileostomy or colostomy * Patients on immunosuppressants (calcineurin inhibitors, prednisone ≥ 20 mg/day, methotrexate, azathioprine, immunosuppressive biologics, JAK inhibitors). * Patients with neutropenia (an absolute neutrophil count \< 0.5 x 10 9 cells/L)

Outcomes

Primary Outcomes

Donor engraftment comparison

The difference in donor microbiota engraftment between the three study groups at week 12

Time frame: Week 12

Secondary Outcomes

Safety of MTT with antibiotic preconditioning and fiber supplementation in patients with PAH

The difference in frequency of serious adverse events and other adverse events between the three study groups

Time frame: Week 12

Feasibility of MTT with antibiotic preconditioning and fiber supplementation in patients with PAH

The differences in proportion of subjects taking 100% of the MTT per protocol between the three study groups

Time frame: Week 12

Change in inflammatory markers

The differences in the change in circulating markers of inflammation (serum CRP and cytokine levels) and microbial metabolites (short chain fatty acids, secondary bile acids, and trimethylamine oxide) from baseline to week 12 between the three study groups.

Time frame: From Baseline to Week 12

Compare right ventricular function, measure 1

The differences in the change in six-minute walk distance (6MWD) from baseline to week 12 between the three study groups

Time frame: Week 12

Compare right ventricular function

The differences in the change in right ventricular ejection fraction from baseline to week 12 between the three study groups

Time frame: Week 12

Compare right ventricular function

The differences in the change in quality of life survey from baseline to week 12 between the three study groups

Time frame: Week 12

Microbiota Transplant With Antibiotic Preconditioning and Fiber Supplementation in PAH.

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts