NCT04884971

Microbiota Transplant Therapy for Pulmonary Arterial Hypertension: Early Safety and Feasibility Study

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 11 (actual)
• Sponsor: University of Minnesota · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

This pilot clinical trial will evaluate the initial safety and feasibility of intestinal microbiota transplantation (IMT) in patients with pulmonary arterial hypertension (PAH). This trial will inform development of future trials in treatment of PAH. Active drug in capsule form composed of freeze-dried, encapsulated intestinal microbiota from healthy donors will be administered to patients with PAH. This study will also allow for limited evaluation of pharmacokinetics in terms of donor microbiota engraftment and pharmacodynamics in terms of potential mechanisms. It will also allow for limited evaluation of cardiac endurance and function prior to and after IMT.

Detailed description

Pulmonary arterial hypertension (PAH) is a chronic disease characterized by pulmonary vascular remodeling of precapillary pulmonary arteries resulting in obstruction, increased pulmonary vascular resistance, right-sided cardiac failure, and ultimately death. Although pharmacologic therapies have been developed, these modestly improve cardiac function and primarily act to improve symptoms and quality of life; therefore, PAH remains a very lethal disease. Perivascular lung inflammation drives these vascular changes in PAH. This inflammatory profile could be driven by an imbalance of pro- and anti-inflammatory intestinal microbial metabolites, cytokines, other mediators, and/or direct effects of circulating bacteria all stemming from dysbiosis, gut-barrier dysfunction, and possibly, decreased hepatic filtration. Because PAH is characterized by a microbiome distinct from healthy controls, the investigators hypothesize that intestinal microbiota transplant (IMT) will help to reduce severity of PAH and improve quality of life, and that the healthy microbiome may exert these effects by decreasing inflammation. In this pilot clinical trial, the investigators aim to test the safety and feasibility of IMT from healthy donors into patients with PAH. Additionally, in the exploratory objectives, the investigators will obtain limited data to study pharmacokinetics of IMT, including engraftment and stability of donor intestinal microbiota, and pharmacodynamics to include circulating microbial products and markers of inflammation. Proposed circulating markers that may be assessed include interleukin-6, C-reactive protein, soluble CD14, lipopolysaccharide (LPS), phenylacetylglutamine, trimethylamine N-oxide, intestinal fatty acid binding protein, zonulin, claudin, short-chain fatty acids (SCFAs), tumor necrosis factor-α, interleukin-1β, and transforming growth factor-β.

Conditions

• Pulmonary Arterial Hypertension

Interventions

Type	Name	Description
DRUG	Intestinal microbiota transplant (IMT)	Two size 00 capsules from a single lot will be taken daily. Approximately 2.0 x 10\^11 bacteria from a healthy donor are contained in each capsule.

Timeline

• Start date: 2021-11-03
• Primary completion: 2023-12-31
• Completion: 2023-12-31
• First posted: 2021-05-13
• Last updated: 2024-02-12

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study