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

NCT ID: NCT04884971

Last Updated: 2024-02-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-03
• Study Completion Date: 2023-12-31

Brief 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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Microbiota Treatment Arm

Participants will receive the encapsulated microbiota intervention daily for seven days and will be subsequently monitored for six months.

Group Type: EXPERIMENTAL

Intestinal microbiota transplant (IMT)

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Diagnosis of pulmonary arterial hypertension (PAH)
• On stable treatment for PAH for one month prior to enrollment
• Able to swallow capsultes
• Able to provide blood sample and fecal sample

Exclusion Criteria

• Dysphagia to pills
• Clinically active inflammatory bowel disease
• Pregnancy or breastfeeding
• Life expectancy of <6 months
• Presence of ileostomy or colostomy
• Taking immunosuppressants (calcineurin inhibitors, prednisone greater than or equal to 20mg/day, methotrexate, azathioprine, immunosuppressive biologics, JAK inhibitors)
• Neurotropenia (an absolute neurotrophil count < 0.5 x 10^9 cells/L)
• History of solid organ or bone marrow transplant
• Anticipated recurrent antibiotic use (participants with frequent urinary tract infections or sinusitis)
• History of severe anaphylactic food allergy
• History of celiac disease
• History of receiving cancer chemotherapy, immunotherapy, or radiation

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Minnesota

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thenappan Thenappan, MD

Role: PRINCIPAL_INVESTIGATOR

University of Minnesota Division of Cardiology

Kurt Prins, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Minnesota Division of Cardiology

Edward Weir, MD

Role: PRINCIPAL_INVESTIGATOR

University of Minnesota Division of Cardiology

Alexander Khoruts, MD

Role: PRINCIPAL_INVESTIGATOR

University of Minnesota Division of Gastroenterology

Locations

University of Minnesota

Minneapolis, Minnesota, United States

Countries

United States

References

Moutsoglou D, Blake M, Belhasan DC, Peichel G, Vang BM, Weir EK, Lopez S, Prins KW, Kabage AJ, Prisco SZ, Kremer BP, Khoruts A, Thenappan T. Microbiota Transplant Therapy Is Safe and Feasible in Pulmonary Arterial Hypertension. JACC Basic Transl Sci. 2025 Sep;10(9):101347. doi: 10.1016/j.jacbts.2025.101347. Epub 2025 Aug 12.

Reference Type: DERIVED

PMID: 40803054 (View on PubMed)

Other Identifiers

CV-2021-29604

Identifier Type: -

Identifier Source: org_study_id