- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04884971
Microbiota Transplant Therapy for Pulmonary Arterial Hypertension: Early Safety and Feasibility Study
February 9, 2024 updated by: University of Minnesota
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
11
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Daphne Moutsoglou, MD, PhD
- Phone Number: 612-899-6344
- Email: dmmoutso@umn.edu
Study Contact Backup
- Name: Thenappan Thenappan, MD
- Phone Number: 612-899-2722
- Email: tthenapp@umn.edu
Study Locations
-
-
Minnesota
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Minneapolis, Minnesota, United States, 55455
- University of Minnesota
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 75 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / 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.
|
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
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6 months
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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.
|
6 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- 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
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
November 3, 2021
Primary Completion (Actual)
December 31, 2023
Study Completion (Actual)
December 31, 2023
Study Registration Dates
First Submitted
May 7, 2021
First Submitted That Met QC Criteria
May 7, 2021
First Posted (Actual)
May 13, 2021
Study Record Updates
Last Update Posted (Actual)
February 12, 2024
Last Update Submitted That Met QC Criteria
February 9, 2024
Last Verified
February 1, 2024
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CV-2021-29604
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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