Microbiota Transplant Therapy for Pulmonary Arterial Hypertension: Early Safety and Feasibility Study
Condition: Pulmonary Arterial Hypertension
MeSH terms: Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Hypertension
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): Intestinal microbiota transplant (IMT)
Intervention type(s): Drug
Intervention description(s): 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.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment