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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04884971
Recruitment Status : Recruiting
First Posted : May 13, 2021
Last Update Posted : December 3, 2021
Information provided by (Responsible Party):
University of Minnesota

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.

Condition or disease Intervention/treatment Phase
Pulmonary Arterial Hypertension Drug: Intestinal microbiota transplant (IMT) Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Microbiota Transplant Therapy for Pulmonary Arterial Hypertension: Early Safety and Feasibility Study
Actual Study Start Date : November 3, 2021
Estimated Primary Completion Date : December 2023
Estimated Study Completion Date : December 2023

Arm Intervention/treatment
Experimental: Microbiota Treatment Arm
Participants will receive the encapsulated microbiota intervention daily for seven days and will be subsequently monitored for six months.
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.

Primary Outcome Measures :
  1. Frequency of Serious Adverse Events [ Time Frame: 6 months ]
    In order to assess the safety of the trial, the frequency of adverse events will be reported. Outcome will be reported as the mean number of serious adverse events per participant.

  2. Proportion of IMT Compliance [ Time Frame: 6 months ]
    In order to assess the feasibility of the trial, the proportion of subjects taking 100% of the intestinal microbiota transplantation (IMT) doses per protocol will be reported. Outcome is reported as the percent of participants who consume 100% of IMT doses.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04884971

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Contact: Daphne Moutsoglou, MD, PhD 612-899-6344
Contact: Thenappan Thenappan, MD 612-899-2722

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United States, Minnesota
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
University of Minnesota
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Principal Investigator: Daphne Moutsoglou, MD, PhD University of Minnesota Division of Gastroenterology
Principal Investigator: Thenappan Thenappan, MD University of Minnesota Division of Cardiology
Principal Investigator: Kurt Prins, MD, PhD University of Minnesota Division of Cardiology
Principal Investigator: Edward Weir, MD University of Minnesota Division of Cardiology
Principal Investigator: Alexander Khoruts, MD University of Minnesota Division of Gastroenterology
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Responsible Party: University of Minnesota Identifier: NCT04884971    
Other Study ID Numbers: CV-2021-29604
First Posted: May 13, 2021    Key Record Dates
Last Update Posted: December 3, 2021
Last Verified: December 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Pulmonary Arterial Hypertension
Familial Primary Pulmonary Hypertension
Vascular Diseases
Cardiovascular Diseases
Hypertension, Pulmonary
Lung Diseases
Respiratory Tract Diseases