Clinical trial NCT06481852: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Pulmonary Arterial Hypertension
Lead sponsor: University of Minnesota
Sponsor class: OTHER
First posted: 2024-07-01
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.


Eligibility criteria: 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

Primary outcomes:
measure: donor engraftment comparison
timeFrame: week 12
Secondary outcomes:
measure: safety of MTT with antibiotic preconditioning and fiber supplementation in patients with PAH
timeFrame: week 12
measure: feasibility of MTT with antibiotic preconditioning and fiber supplementation in patients with PAH
timeFrame: week 12
measure: change in inflammatory markers
timeFrame: week 12
measure: compare right ventricular function, measure 1
timeFrame: week 12
measure: compare right ventricular function
timeFrame: week 12
measure: compare right ventricular function
timeFrame: week 12
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
Study officials:
affiliation: University of Minnesota
name: Thenappan Thenappan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Minnesota
name: Levi Teigen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Minnesota
name: Alexander Khoruts, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Minnesota
name: Christopher Staley, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Minnesota
name: Kurt Prins, MD,PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Minnesota
name: Edward Weirs, MD
role: PRINCIPAL_INVESTIGATOR
References: