Pulmonary Arterial HypertensionPhase 1NCT04884971
Microbiota Transplant Therapy for Pulmonary Arterial Hypertension: Early Safety and Feasibility Study
A Phase 1 study testing Intestinal microbiota transplant (IMT) in people with Pulmonary Arterial Hypertension, run by University of Minnesota at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Pulmonary Arterial Hypertension
- What is being tested?
- Intestinal microbiota transplant (IMT)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Nov 2021to 31 Dec 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Minnesota
Minneapolis, Minnesota, 55455
About this study
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.
Read the 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
- Being tested
- Intestinal microbiota transplant (IMT)
- Medical subject headings
- Pulmonary Arterial Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intestinal microbiota transplant (IMT)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.
| Study group | Role | What they receive |
|---|---|---|
| Microbiota Treatment Arm | Experimental | Participants will receive the encapsulated microbiota intervention daily for seven days and will be subsequently monitored for six months. Receives: Drug: Intestinal microbiota transplant (IMT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency of Serious Adverse Events
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.
Measured: 6 months
Proportion of IMT Compliance
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.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2021
- Study start3 Nov 2021
- Primary completion31 Dec 2023
- Study completion31 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
- More trials run by University of MinnesotaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Thenappan Thenappan, MD, Principal investigator, University of Minnesota Division of CardiologyKurt Prins, MD, PhD, Principal investigator, University of Minnesota Division of CardiologyEdward Weir, MD, Principal investigator, University of Minnesota Division of CardiologyAlexander Khoruts, MD, Principal investigator, University of Minnesota Division of Gastroenterology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04884971
- Sponsor's protocol ID
- CV-2021-29604
- Status last verified
- Feb 2024
- First submitted
- 7 May 2021
- Last updated
- 12 Feb 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 40803054
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Microbiota Transplant Therapy for Pulmonary Arterial Hypertension: Early Safety and Feasibility Study
- ClinicalTrials.gov ID
- NCT04884971
- Acronym / sponsor ID
- CV-2021-29604
- Conditions
- Pulmonary Arterial Hypertension
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- University of MinnesotaUniversity, hospital or other
- Study start
- 3 Nov 2021 (actual)
- Primary completion
- 31 Dec 2023 (actual)
- Study completion
- 31 Dec 2023 (actual)
- First posted
- 13 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Microbiota Treatment Arm | Experimental | Drug: Intestinal microbiota transplant (IMT)Participants will receive the encapsulated microbiota intervention daily for seven days and will be subsequently monitored for six months. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (12 listed)
- Dysphagia to pills
- Clinically active inflammatory bowel disease
- Pregnancy or breastfeeding
- Life expectancy of <6 months
- Presence of ileostomy or colostomy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Drug | Microbiota Treatment Arm |
Primary outcome
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.
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2024.
- Derived from this study: PubMed 40803054Moutsoglou 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Thenappan Thenappan, MD principal investigator
University of Minnesota Division of Cardiology
Kurt Prins, MD, PhD principal investigator
University of Minnesota Division of Cardiology
Edward Weir, MD principal investigator
University of Minnesota Division of Cardiology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Intestinal microbiota transplant (IMT) in people with Pulmonary Arterial Hypertension, run by University of Minnesota at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Frequency of Serious Adverse Events (time frame: 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04884971, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Feb 2024.