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

NCT06481852 | Recruiting Phase 1 FDA Drug

• 1 other identifier: CV-2024-32994
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Pulmonary Arterial Hypertension

Outcome Measures

Primary Outcomes (1)

• donor engraftment comparison

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

  week 12

Secondary Outcomes (6)

• safety of MTT with antibiotic preconditioning and fiber supplementation in patients with PAH

  week 12

• feasibility of MTT with antibiotic preconditioning and fiber supplementation in patients with PAH

  week 12

• change in inflammatory markers

  week 12

• compare right ventricular function, measure 1

  week 12

• compare right ventricular function

  week 12

Study Arms (3)

Drug group

EXPERIMENTAL

PAH patients randomized to MTT with antibiotic preconditioning + fiber supplementation

Drug: MTT with antibiotic preconditioning + fiber supplementation

Control 1

ACTIVE COMPARATOR

MTT with antibiotic preconditioning + placebo supplementation

Drug: MTT with antibiotic preconditioning + placebo supplementation

Control 2

PLACEBO COMPARATOR

placebo + placebo supplementation.

Other: MTT with placebo + placebo supplementation.

Interventions

MTT with antibiotic preconditioning + fiber supplementation DRUG

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.

Drug group

MTT with antibiotic preconditioning + placebo supplementation DRUG

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.

Control 1

MTT with placebo + placebo supplementation. OTHER

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.

Control 2

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Minnesota: lead

Study Sites (1)

University of Minnesota

Minneapolis, Minnesota, 55414, United States

RECRUITING

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

monooxyethylene trimethylolpropane tristearate

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Thenappan Thenappan, MD

  University of Minnesota

  PRINCIPAL INVESTIGATOR

• Levi Teigen, MD, PhD

  University of Minnesota

  PRINCIPAL INVESTIGATOR

• Alexander Khoruts, MD

  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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gretchen Peichel

CONTACT

gpeichel@umn.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 24, 2024
• First Posted: July 1, 2024
• Study Start: October 28, 2024
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): April 30, 2027
• Last Updated: October 15, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)