A Pilot Study of Microbiota Transplant With Antibiotic Preconditioning and Fiber Supplementation in Pulmonary Arterial Hypertension (GUT RESTORE-PAH)

Обзор

This pilot clinical trial will evaluate the initial safety, feasibility, and pharmacokinetics of microbiota transplant therapy (MTT) with antibiotic pre-conditioning and fiber supplementation vs. placebo in patients with pulmonary arterial hypertension (PAH). This trial will inform development of future trials of MTT as a treatment for PAH. 24 PAH patients will be randomized to receive either MTT with antibiotic preconditioning + fiber supplementation, MTT with antibiotic preconditioning + placebo supplementation, or placebo + placebo supplementation. MTT will in a capsule form composed of freeze-dried, encapsulated intestinal microbiota from healthy donors. Fiber supplementation will be 10-14 gm oral fiber supplement. Patients will be followed at week 1, week 2, week 4, week 12, and week 24. Patient will undergo stool sample collection at baseline, week 1, week 4, and week 12, blood sample collection at baseline, week 4, and week,12. In addition, patient will undergo an echocardiogram, six-minute walk test (6MWT) and quality of life questionnaire at baseline and at week 12.

Вмешательства

• Препарат MTT with antibiotic preconditioning + fiber supplementation
  MTT will in a capsule form composed of freeze-dried, encapsulated intestinal microbiota from healthy donors. Fiber supplementation will be 10-14 gm oral fiber supplement. Patients will be followed at week 1, week 2, week 4, week 12, and week 24. Patient will undergo stool sample collection at baseline, week 1, week 4, and week 12, blood sample collection at baseline, week 4, and week, 12. In addition, patient will undergo an echocardiogram, six-minute walk test (6MWT) and quality of life questio
• Препарат MTT with antibiotic preconditioning + placebo supplementation
  MTT will in a capsule form composed of freeze-dried, encapsulated intestinal microbiota from healthy donors. Patients will be followed at week 1, week 2, week 4, week 12, and week 24. Patient will undergo stool sample collection at baseline, week 1, week 4, and week 12, blood sample collection at baseline, week 4, and week, 12. In addition, patient will undergo an echocardiogram, six-minute walk test (6MWT) and quality of life questionnaire at baseline and at week 12.
• Другое MTT with placebo + placebo supplementation.
  MTT will in a capsule form composed of freeze-dried, encapsulated intestinal microbiota from healthy donors. Patients will be followed at week 1, week 2, week 4, week 12, and week 24. Patient will undergo stool sample collection at baseline, week 1, week 4, and week 12, blood sample collection at baseline, week 4, and week, 12. In addition, patient will undergo an echocardiogram, six-minute walk test (6MWT) and quality of life questionnaire at baseline and at week 12.

Первичные конечные точки

• donor engraftment comparison [Срок оценки: week 12]

Вторичные конечные точки (6)

• safety of MTT with antibiotic preconditioning and fiber supplementation in patients with PAH [Срок оценки: week 12]
• feasibility of MTT with antibiotic preconditioning and fiber supplementation in patients with PAH [Срок оценки: week 12]
• change in inflammatory markers [Срок оценки: week 12]
• compare right ventricular function, measure 1 [Срок оценки: week 12]
• compare right ventricular function [Срок оценки: week 12]
• compare right ventricular function [Срок оценки: week 12]

Критерии участия

Критерии включения

• Provision of signed and dated consent form
• Ages 18-75
• Diagnosis of PAH
• On stable treatment for PAH for one month prior to enrollment
• Able to swallow capsules
• Able to provide blood sample and fecal sample
• Stated willingness to comply with all study procedures and availability for the duration of trial to follow-up by telephone, in-person, email, and/or video visits or correspondence.

Критерии исключения

• Dysphagia to pills
• Clinically active inflammatory bowel disease
• Pregnancy or breastfeeding. A pregnancy test will be obtained from females of child- bearing potential at the screening visit or day 1 (prior to the receipt of MTT). Patients with a positive pregnancy test will be excluded. A negative result will be required for subjects who are females of child-bearing potential to receive MTT. Patients will be counseled to avoid pregnancy which is the standard of care for patients with PAH.
• Life expectancy of < 6 months
• Presence of ileostomy or colostomy
• Patients on immunosuppressants (calcineurin inhibitors, prednisone ≥ 20 mg/day, methotrexate, azathioprine, immunosuppressive biologics, JAK inhibitors).
• Patients with neutropenia (an absolute neutrophil count < 0.5 x 10 9 cells/L) obtained on a complete blood count with differential at screening
• History of solid organ or bone marrow transplant
• Anticipated recurrent antibiotic use (patients with frequent urinary tract infections or sinusitis)
• History of severe anaphylactic food allergy
• History of celiac disease
• Patients receiving cancer chemotherapy, immunotherapy, or radiation
• Patients with severe Irritable bowel syndrome (IBS) defined by an IBS score >250

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Поддерживающая терапия

Центры проведения

США · 1 центр

• University of Minnesota — Minneapolis

Идентификаторы

NCT: NCT06481852 · CV-2024-32994

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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