A Pilot Study of Microbiota Transplant With Antibiotic Preconditioning and Fiber Supplementation in Pulmonary Arterial Hypertension (GUT RESTORE-PAH).
Trial Snapshot
- Phase
- Phase 1
- Status
- Active, not recruiting
- Sponsor
- University of Minnesota
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- Donor engraftment comparison
Study Overview
Brief Summary
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 Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Supportive Care
- Masking
- Double (Participant, Outcomes Assessor)
Masking Description
Double (Participant, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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)
Arms & Interventions
Drug Group
PAH patients randomized to MTT with antibiotic preconditioning + fiber supplementation
Intervention: MTT with antibiotic preconditioning + fiber supplementation (Drug)
Control 1
MTT with antibiotic preconditioning + placebo supplementation
Intervention: MTT with antibiotic preconditioning + placebo supplementation (Drug)
Control 2
placebo + placebo supplementation.
Intervention: MTT with placebo + placebo supplementation. (Drug)
Outcomes
Primary Outcomes
Donor engraftment comparison
Time Frame: Week 12
The difference in donor microbiota engraftment between the three study groups at week 12
Secondary Outcomes
- 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(From Baseline to Week 12)
- Compare right ventricular function, measure 1(Week 12)
- Compare right ventricular function(Week 12)