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

University of Minnesota (UMN)

Status and phase: Enrolling; Phase 1

Conditions: Pulmonary Arterial Hypertension

Treatments: Other: MTT with placebo + placebo supplementation.; Drug: MTT with antibiotic preconditioning + placebo supplementation; Drug: MTT with antibiotic preconditioning + fiber supplementation

Study type: Interventional

Funder types: Other

Identifiers

NCT06481852

CV-2024-32994

Details and patient eligibility

About

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.

Enrollment: 24 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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24 participants in 3 patient groups, including a placebo group

Drug group

Experimental group

Description:

PAH patients randomized to MTT with antibiotic preconditioning + fiber supplementation

Treatment:

Drug: MTT with antibiotic preconditioning + fiber supplementation

Control 1

Active Comparator group

Description:

MTT with antibiotic preconditioning + placebo supplementation

Treatment:

Drug: MTT with antibiotic preconditioning + placebo supplementation

Control 2

Placebo Comparator group

Description:

placebo + placebo supplementation.

Treatment:

Other: MTT with placebo + placebo supplementation.