Pulmonary Arterial Hypertension
Conditions
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.
Interventions
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.
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.
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.
Sponsors
University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
Double (Participant, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Donor engraftment comparison | Week 12 | The difference in donor microbiota engraftment between the three study groups at week 12 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| Change in inflammatory markers | From Baseline to Week 12 | The differences in the change in circulating markers of inflammation (serum CRP and cytokine levels) and microbial metabolites (short chain fatty acids, secondary bile acids, and trimethylamine oxide) 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 right ventricular ejection fraction from baseline to week 12 between the three study groups |
Countries
United States
Contacts
CONTACTGretchen Peichel
CONTACTThenappan Thenappan, MD
PRINCIPAL_INVESTIGATORLevi Teigen, MD, PhD
University of Minnesota
PRINCIPAL_INVESTIGATORThenappan Thenappan, MD
University of Minnesota
PRINCIPAL_INVESTIGATORAlexander Khoruts, MD
University of Minnesota
PRINCIPAL_INVESTIGATORChristopher Staley, PhD
University of Minnesota
PRINCIPAL_INVESTIGATORKurt Prins, MD,PhD
University of Minnesota
PRINCIPAL_INVESTIGATOREdward Weirs, MD
University of Minnesota
Outcome results
None listed