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

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.

Study Overview

• Status: Recruiting
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: MTT with antibiotic preconditioning + fiber supplementation; Drug: MTT with antibiotic preconditioning + placebo supplementation; Other: MTT with placebo + placebo supplementation.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Gretchen Peichel; Email: gpeichel@umn.edu

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55414
      • Recruiting
      • University of Minnesota
      • Contact: Gretchen Peichel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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
• Patients with severe Irritable bowel syndrome (IBS) defined by an IBS score >250

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Drug group; PAH patients randomized to MTT with antibiotic preconditioning + fiber supplementation	Drug: MTT with antibiotic preconditioning + fiber 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.
Active Comparator: Control 1; MTT with antibiotic preconditioning + placebo supplementation	Drug: MTT with antibiotic preconditioning + placebo supplementation; 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.
Placebo Comparator: Control 2; placebo + placebo supplementation.	Other: MTT with placebo + placebo supplementation.; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
donor engraftment comparison	The difference in donor microbiota engraftment between the three study groups at week 12	week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	week 12
change in inflammatory markers	The differences in the change in circulating markers of inflammation and microbial metabolites from baseline to week 12 between the three study groups	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	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	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	week 12

Collaborators and Investigators

• Sponsor: University of Minnesota
• Investigators: Principal Investigator: Thenappan Thenappan, MD, University of Minnesota; Principal Investigator: Alexander Khoruts, MD, University of Minnesota; Principal Investigator: Levi Teigen, MD, PhD, University of Minnesota; Principal Investigator: Christopher Staley, PhD, University of Minnesota; Principal Investigator: Kurt Prins, MD,PhD, University of Minnesota; Principal Investigator: Edward Weirs, MD, University of Minnesota

Study record dates

Study Major Dates

• Study Start (Actual): October 28, 2024
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): April 30, 2027

Study Registration Dates

• First Submitted: June 24, 2024
• First Submitted That Met QC Criteria: June 28, 2024
• First Posted (Actual): July 1, 2024

Study Record Updates

• Last Update Posted (Estimated): October 15, 2025
• Last Update Submitted That Met QC Criteria: October 10, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Pulmonary Arterial Hypertension; Anti-Infective Agents; Antitubercular Agents; monooxyethylene trimethylolpropane tristearate
• Other Study ID Numbers: CV-2024-32994

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No