Microbiota Transplant Therapy for Pulmonary Hypertension

Overseen By Gretchen Peichel

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Minnesota

Must not be taking: Immunosuppressants, Chemotherapy

Disqualifiers: Pregnancy, Inflammatory bowel disease, others

Compensation: Varies

Number of Visits: 25

Duration: 12 weeks

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for pulmonary arterial hypertension (PAH), a condition where high blood pressure affects arteries in the lungs. Researchers aim to determine if microbiota transplant therapy (MTT), delivered in capsules, is safe and can be absorbed by the body. Participants will receive either MTT with a fiber supplement, MTT with a placebo, or a full placebo treatment. Individuals living with PAH and on stable treatments might be suitable for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but you must be on stable treatment for pulmonary arterial hypertension for at least one month before joining. If you are on immunosuppressants or receiving cancer treatments, you cannot participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Earlier studies have found microbiota transplant therapy (MTT) to be safe for people with pulmonary arterial hypertension (PAH). Research shows that patients tolerated the treatment well, with no major safety problems reported. Some studies even observed reduced inflammation and improved quality of life. This therapy uses gut bacteria from healthy donors, and some participants experienced modest benefits. As this trial is in an early stage, it primarily focuses on safety and determining the right dose. Researchers continue to collect more data to confirm these early results. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for pulmonary hypertension, which often involve medications like endothelin receptor antagonists or phosphodiesterase-5 inhibitors, the investigational therapy being explored here is Microbiota Transplant Therapy (MTT). MTT is unique because it leverages the power of gut microbiota, which is a completely different approach from traditional drugs that target the blood vessels or heart function directly. Researchers are excited about MTT because it includes antibiotic preconditioning and fiber supplementation, which could reshape the gut environment and potentially offer a novel way to manage pulmonary hypertension. This approach might not only impact the lungs but also improve overall gut health, providing a dual benefit that traditional therapies do not offer.

What evidence suggests that this trial's treatments could be effective for pulmonary hypertension?

Research suggests that microbiota transplant therapy (MTT) could benefit people with pulmonary arterial hypertension (PAH). This treatment transfers healthy gut bacteria to patients to enhance their health. In this trial, participants will be randomized into different treatment arms. One group will receive MTT with antibiotic preconditioning and fiber supplementation, while another will receive MTT with antibiotic preconditioning and placebo supplementation. A third group will receive a placebo with placebo supplementation. Some studies have shown that MTT is safe for people with PAH. The healthy bacteria might help reduce symptoms by positively affecting the body. While more research is needed to fully understand its effects, early findings suggest it could be a promising option. ^{4 6 7 8 9}

Who Is on the Research Team?

Kurt Prins, MD,PhD

Principal Investigator

University of Minnesota

Thenappan Thenappan, MD

Principal Investigator

University of Minnesota

Christopher Staley, PhD

Principal Investigator

University of Minnesota

Edward Weirs, MD

Principal Investigator

University of Minnesota

Levi Teigen, MD, PhD

Principal Investigator

University of Minnesota

Alexander Khoruts, MD

Principal Investigator

University of Minnesota

Are You a Good Fit for This Trial?

This trial is for adults aged 18-75 with pulmonary arterial hypertension (PAH) who have been on stable PAH treatment for at least a month. Participants must be able to swallow capsules, provide blood and stool samples, and commit to the study's schedule including follow-ups.

Inclusion Criteria

I can provide blood and stool samples.

I have signed and agreed to the consent form.

I have been on a stable treatment for PAH for at least one month.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive microbiota transplant therapy (MTT) with antibiotic preconditioning and fiber supplementation or placebo

12 weeks

Visits at week 1, week 2, week 4, and week 12

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Visit at week 24

What Are the Treatments Tested in This Trial?

Interventions

• MTT with antibiotic preconditioning + fiber supplementation
• MTT with antibiotic preconditioning + placebo supplementation
• MTT with placebo + placebo supplementation

Trial Overview The trial tests microbiota transplant therapy (MTT) with antibiotic preconditioning and fiber supplementation versus placebo in PAH patients. It aims to assess safety, feasibility, and how the body processes MTT. Patients are randomly assigned to one of three groups: MTT plus fiber, MTT plus placebo fiber or double placebo.

How Is the Trial Designed?

Group I: Drug group Experimental Treatment 1 Intervention

PAH patients randomized to MTT with antibiotic preconditioning + fiber supplementation

Group II: Control 1 Active Control 1 Intervention

MTT with antibiotic preconditioning + placebo supplementation

Group III: Control 2 Placebo Group 1 Intervention

placebo + placebo supplementation.

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

Published Research Related to This Trial

Fecal microbiota transplantation (FMT) is effective in treating recurrent Clostridium difficile infections, as demonstrated in a case study of a woman who was successfully treated with this method.

The case raises concerns about potential side effects, such as new-onset obesity, when using stool from overweight donors, suggesting the need for further research on the impact of donor characteristics on FMT outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weight gain after fecal microbiota transplantation. Alang, N., Kelly, CR.[2022]

Fecal microbiota transplantation (FMT) is highly effective and considered safe for treating recurrent Clostridium difficile infections, even in patients with complex medical conditions like tetraplegia.

In this case, a self-advancing nasal jejunal feeding tube was successfully used for a minimally invasive FMT, but the patient experienced persistent arterial hypertension post-procedure, suggesting a potential new side effect and a possible link between the intestinal microbiome and blood pressure regulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-invasive fecal microbiota transplantation for recurrent Clostridium difficile infection in a patient presenting with hypertensive disorder post interventionem. Goeser, F., Schlabe, S., Ruiner, CE., et al.[2020]

Pulmonary arterial hypertension (PAH) in rats leads to gut dysbiosis, characterized by a three-fold increase in the Firmicutes-to-Bacteroidetes ratio, indicating an imbalance in gut bacteria.

The altered microbiota composition in PAH rats, along with reduced serum acetate levels, suggests that these changes could contribute to the disease's pathophysiology by affecting immune, hormonal, and metabolic functions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulmonary Arterial Hypertension Affects the Rat Gut Microbiome. Callejo, M., Mondejar-Parreño, G., Barreira, B., et al.[2019]

The study found that gut microbiota is disrupted in rat models of pulmonary hypertension induced by hypoxia, hypoxia/Sugen5416, and monocrotaline, indicating a potential link between gut health and pulmonary hypertension.

Specific changes in gut microbiota diversity were observed, with distinct patterns in different models of pulmonary hypertension, and six plasma biomarkers associated with the condition were identified, suggesting a complex relationship between gut microbiota and disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gut Microbiota and Metabolome Changes in Three Pulmonary Hypertension Rat Models. Luo, L., Yin, H., Gou, D.[2023]

Fecal microbiota transplantation (FMT) has a total adverse event (AE) incidence rate of 28.5%, with abdominal discomfort being the most common AE reported in 19 studies, highlighting the need for careful monitoring during the procedure.

Serious adverse events (SAEs) occurred in 9.2% of patients, with a notable incidence of death (3.5%) and infections (2.5%), indicating that while FMT can be beneficial, it carries significant risks that require further investigation through high-quality randomized controlled trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Review: Adverse Events of Fecal Microbiota Transplantation. Wang, S., Xu, M., Wang, W., et al.[2023]

Fecal microbiota transplantation (FMT) is a safe and effective treatment for recurrent Clostridium difficile infections and may also help in understanding the link between gut microbiota dysbiosis and cardiovascular and metabolic disorders.

This study provides a detailed protocol for conducting FMT in murine models, which can aid in exploring gut microbiome effects on cardiovascular disease and potentially lead to new microbiota-targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Murine Fecal Isolation and Microbiota Transplantation. Ishimwe, JA., Zhong, J., Kon, V., et al.[2023]

Gut microbiota dysbiosis contributes to the development of pulmonary arterial hypertension (PAH) by increasing gut permeability and allowing harmful bacterial products to enter the bloodstream, which exacerbates inflammation and vascular remodeling.

Emerging therapies like probiotic treatment and fecal microbiota transplantation show promise in complementing existing PAH treatments, highlighting the potential of targeting gut health in managing this serious condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role and Mechanism of Gut Microbiota in Pulmonary Arterial Hypertension. Chen, YH., Yuan, W., Meng, LK., et al.[2022]

Fecal microbiota transplantation (FMT) is a cost-effective treatment for recurrent Clostridium difficile infection (rCDI), with all economic evaluations showing it to be more cost-effective than other standard treatments at a threshold of ≤$50,000 per quality-adjusted life year (QALY).

The systematic review included 9 high-quality economic evaluations, primarily focusing on rCDI and inflammatory bowel disease (IBD), indicating that while FMT is effective for rCDI, further studies are needed to explore its economic impact for other conditions like IBD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review of economic evaluation in fecal microbiota transplantation. Stalder, T., Kapel, N., Diaz, S., et al.[2021]

Fecal microbiota transplantation (FMT) is a safe and effective treatment for recurrent Clostridium difficile infections, and research is expanding to explore its potential for treating other conditions related to chronic inflammation and autoimmunity.

Current studies on FMT for conditions like ulcerative colitis and metabolic syndrome show promise, but many lack rigorous methodology, highlighting the need for more standardized and well-designed trials to validate these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Fecal microbiota transplantation : current status and prospects]. Gilbert, B., Schrenzel, J.[2019]

Mesenchymal stem cell (MSC) therapy effectively reduces pulmonary hypertension (PH) in hypoxia-induced mice, suggesting a potential new treatment avenue for this condition.

The study found that MSC treatment restores gut microbiota balance, reversing harmful bacterial increases and enhancing beneficial bacteria, indicating that gut microbiota may play a significant role in the therapeutic mechanism of MSCs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MSCs Therapy Reverse the Gut Microbiota in Hypoxia-Induced Pulmonary Hypertension Mice. Luo, L., Chen, Q., Yang, L., et al.[2021]

Fecal microbiota transplantation (FMT) using targeted colonic release capsules (FMTcr) showed a slightly higher clinical cure rate for recurrent Clostridium difficile infection (rCDI) at 80.6% compared to 75% for gastric release capsules (FMTgr), although the difference was not statistically significant.

Both FMT formulations were found to be safe with no serious adverse events, but FMTcr was more effective in increasing gut microbial diversity, suggesting better microbial engraftment patterns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplantation Capsules with Targeted Colonic Versus Gastric Delivery in Recurrent Clostridium difficile Infection: A Comparative Cohort Analysis of High and Lose Dose. Allegretti, JR., Fischer, M., Sagi, SV., et al.[2020]

Fecal microbiota transplantation (FMT) shows a higher response rate compared to medical therapy (MT) specifically for recurrent Clostridium difficile infections (RCDI), suggesting it may be a more effective treatment option for these patients.

However, FMT does not demonstrate a significant advantage over MT for treating primary Clostridium difficile infections (CDI), indicating that FMT should not be used universally for all CDI patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplantation and Medical Therapy for Clostridium difficile Infection : Meta-analysis of Randomized Controlled Trials. Singh, T., Bedi, P., Bumrah, K., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12361999/

Microbiota Transplant Therapy Is Safe and Feasible in ... The primary outcome was the safety and feasibility of MTT in PAH patients. We did not designate any secondary outcomes. Exploratory outcomes ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06481852

A Placebo-controlled, Randomized Clinical Trial to Assess ... This pilot clinical trial will evaluate the initial safety, feasibility, and pharmacokinetics of microbiota transplant therapy (MTT) with antibiotic ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8865595/

Microbiome Transplant in Pulmonary Arterial Hypertension We plan to determine if microbiota transplant therapy (MTT), also known as fecal microbiota transplant, can treat PAH. This therapy uses purified bacteria from ...

4. withpower.com withpower.com/trial/phase-1-familial-primary-pulmonary-hypertension-8-2024-425f1

Microbiota Transplant Therapy for Pulmonary Hypertension This pilot clinical trial will evaluate the initial safety, feasibility, and pharmacokinetics of microbiota transplant therapy (MTT) with antibiotic ...

5. studyfinder.umn.edu studyfinder.umn.edu/studies/31464

A placebo-controlled, randomized clinical trial to assess ... We are studying whether transplanting gut microbes from healthy donors using a treatment called microbiota transplant therapy may have beneficial effects on ...

6. jacc.org jacc.org/doi/10.1016/j.jacbts.2025.101347

Microbiota Transplant Therapy Is Safe and Feasible in ... The primary outcome was the safety and feasibility of MTT in PAH patients. We did not designate any secondary outcomes. Exploratory outcomes ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40803054/

Microbiota Transplant Therapy Is Safe and Feasible in ... These findings of decreased systemic inflammation with only modest donor engraftment support the potential of MTT as a novel treatment for PAH.

8. sciencedirect.com sciencedirect.com/science/article/pii/S2452302X25003006

Microbiota Transplant Therapy Is Safe and Feasible in ... Though not statistically significantly, MTT was associated with an increase in 6-minute walk distance and an improvement in emPHasis-10 quality of life scores.

9. atsjournals.org atsjournals.org/doi/10.1164/rccm.202108-1833ED

Microbiome Transplant in Pulmonary Arterial Hypertension We plan to determine if microbiota transplant therapy (MTT), also known as fecal microbiota transplant, can treat PAH. This therapy uses purified bacteria from ...