Study Using Prebiotics to Improve Gut Microbiome Diversity After Autologous Cellular Therapy

Официальное название

A Pilot, Randomized, Double-blind, Placebo-controlled Study Using Prebiotics to Improve Gut Microbiome Diversity After Autologous Cellular Therapy in Multiple Myeloma and Lymphoma: The PRIMAL Trial

Обзор

Higher gut microbiome diversity has been associated with improved survival following autologous stem cell transplantation in multiple myeloma and lymphoma. This study hypothesises that prebiotic supplementation with resistant starch (RS) will improve gut microbiome diversity at time of stem cell engraftment. To test this, participants will either have RS or a placebo (maltodextrin) mixed into a food item of their choice for approximately 10 days prior to stem cell infusion and continue to the first day of neutrophil engraftment. The study will look at the difference in gut microbiome diversity between the RS and placebo arm collected at the engraftment timepoint, dietary evaluation to assess the impact of subject diet on microbiome response to intervention and serum sample collection to assess differences to gut permeability during transplant.

Подробное описание

Higher gut microbiome diversity has been associated with improved survival following autologous stem cell transplantation in multiple myeloma and lymphoma, but no strategies have been identified to date that specifically target the gut microbiome. The investigators hypothesize that prebiotic supplementation with resistant starch (RS) will improve gut microbiome diversity at time of stem cell engraftment.

To test this hypothesis, the study will be a randomized, double-blind, placebo-controlled trial of resistant starch versus placebo (maltodextrin) in participants with myeloma or lymphoma undergoing autologous stem cell transplantation. Thirty subjects will be randomized 1:1 to the RS or placebo arm, dosed at 20g daily for 3 days followed by an increased to 20g twice a day mixed into a food item of the participant's choice. The intervention will begin approximately 10 days prior to stem cell infusion and will continue until the first day of neutrophil engraftment (first day absolute neutrophil count \>500) or approximately 30 days in total. Fecal samples will be collected at 4 timepoints for microbiome analysis: 1) at study enrollment 2) day of stem cell infusion 3) day +7 post auto transplant and 4) first day of engraftment defined as absolute neutrophil count \>500 (approximately 10-14 days post-transplant).

The primary endpoint will be the difference in gut microbiome diversity between the RS and placebo arm collected at the engraftment timepoint. Secondary endpoints will include dietary evaluation to assess the impact of subject diet on microbiome response to intervention and serum sample collection to assess differences to gut permeability during transplant.

Вмешательства

• Пищевая добавка Resistant Starch
  A prebiotic nutritional supplement available at commercial grocery and health food stores. Specifically, we will be using Bob's Red Mill® potato starch.
• Пищевая добавка Maltodextrin
  A starch commonly used as a placebo in prebiotic trials that is digested in the stomach and rapidly absorbed

Первичные конечные точки

• Percentage of subjects who adhere to >70% of scheduled doses of the intervention [Срок оценки: 35 Days]

Вторичные конечные точки (4)

• Hospital Duration [Срок оценки: 25 days]
• Rate of Neutropenic Fever [Срок оценки: 25 Days]
• Rate of broad-spectrum antibiotic exposure [Срок оценки: 25 Days]
• Rate of gastrointestinal symptoms [Срок оценки: 35 Days]

Критерии участия

Критерии включения

• Willing to provide informed consent
• Willing to comply with all study procedures and be available for the duration of the study
• Has pathologically confirmed multiple myeloma, Non-Hodgkin lymphoma (DLBCL, mantle cell lymphoma, follicular lymphoma, or peripheral T-cell lymphoma), or Hodgkin lymphoma as determined on medical record review per standard of care transplant procedures (no tissue required for study)
• Meeting a standard-of-care indication for autologous stem cell transplantation for the above diseases as determined by the investigator
• Adult Individuals (male or female) at least 19 years of age
• Meeting indications and recommended for first autologous stem cell transplantation by investigator

Критерии исключения

• History of bariatric surgery (i.e. gastric banding, sleeve gastrectomy, Roux-en-Y bypass), chronic gastrointestinal disease including chronic diarrheal illness or inflammatory bowel disease
• Previous intolerance to fiber supplementation
• Allergy or intolerance to potato starch or maltodextrin
• Subject unwilling to comply with stool sample collection
• Not suitable for study participation due to other reasons at the discretion of the investigators

Eligibility Criteria for CAR T-cell Therapy Cohort

Критерии включения

• Willing to provide informed consent
• Willing to comply with all study procedures and be available for the duration of the study
• Has pathologically confirmed lymphoma or multiple myeloma meeting a commercial indication for CAR-T cell therapy
• Adult Individuals (male or female) at least 19 years of age
• Meeting indications and recommended for CAR-T cell therapy by investigator

Критерии исключения

• History of bariatric surgery (i.e. gastric banding, sleeve gastrectomy, Roux-en-Y bypass), chronic gastrointestinal disease including chronic diarrheal illness or inflammatory bowel disease, or other GI surgery risking diminished effect or tolerance to therapy as determined by investigator
• Previous intolerance to fiber supplementation
• Allergy or intolerance to resistant starch or maltodextrin
• Subject unwilling to comply with stool sample collection
• Not suitable for study participation due to other reasons at the discretion of the investigators

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

Тройное слепое

Основная цель

Поддерживающая терапия

Центры проведения

США · 1 центр

• Unversity of Nebraska Medical Center — Omaha

Идентификаторы

NCT: NCT05135351 · 0821-21-EP

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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