A Placebo-controlled, Randomized Clinical Trial to Assess the Safety, Feasibility, and Pharmacokinetics of Microbiota Transplant Therapy With Antibiotic Preconditioning and Fiber Supplementation in Patients With Pulmonary Arterial Hypertension

Phase 1

Recruiting

• Conditions: Pulmonary Arterial Hypertension
• Interventions: Drug: MTT with antibiotic preconditioning + placebo supplementation; Other: MTT with placebo + placebo supplementation.; Drug: MTT with antibiotic preconditioning + fiber supplementation

• Registration Number: NCT06481852
• Lead Sponsor: University of Minnesota

Brief Summary

This pilot clinical trial 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-06-24
• Study First Submitted QC: 2024-06-28
• Study First Posted: 2024-07-01
• Study Start: 2024-09-01
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-01
• Last Update Posted: 2024-10-03
• Primary Completion: 2026-09-01
• Study Completion: 2026-09-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 24

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) obtained on a complete blood count with differential at screening
• History of solid organ or bone marrow transplant
• Anticipated recurrent antibiotic use (patients with frequent urinary tract infections or sinusitis)
• History of severe anaphylactic food allergy
• History of celiac disease
• Patients receiving cancer chemotherapy, immunotherapy, or radiation

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control 1	MTT with antibiotic preconditioning + placebo supplementation	MTT with antibiotic preconditioning + placebo supplementation
Control 2	MTT with placebo + placebo supplementation.	placebo + placebo supplementation.
Drug group	MTT with antibiotic preconditioning + fiber supplementation	PAH patients randomized to MTT with antibiotic preconditioning + fiber supplementation

Primary Outcome Measures

Name	Time	Method
donor engraftment comparison	week 12	The difference in donor microbiota engraftment between the three study groups at week 12

Secondary Outcome Measures

Name	Time	Method
safety of MTT with antibiotic preconditioning and fiber supplementation in patients with PAH	week 12	The difference in frequency of serious adverse events and other adverse events between the three study groups
change in inflammatory markers	week 12	The differences in the change in circulating markers of inflammation and microbial metabolites from baseline to week 12 between the three study groups
compare right ventricular function, measure 1	week 12	The differences in the change in six-minute walk distance (6MWD) from baseline to week 12 between the three study groups
compare right ventricular function	week 12	The differences in the change in quality of life survey from baseline to week 12 between the three study groups
feasibility of MTT with antibiotic preconditioning and fiber supplementation in patients with PAH	week 12	The differences in proportion of subjects taking 100% of the MTT per protocol between the three study groups

Trial Locations

Locations (1)

University of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States