Effect of 4 Weeks of Oral Probiotic Desulfovibrio Piger Supplementation on Immunological and Metabolic Parameters in Individuals With Longstanding Type 1 Diabetes

Обзор

The goal is to establish the effect of oral probiotic Desulfovibrio piger (D. piger) supplementation on immunological and metabolic parameters in individuals with longstanding type 1 diabetes with residual beta cell function. The investigators will perform a double-blind, randomized, placebo-controlled trial in 2x10 participants to measure effects of D. piger on parameters of systemic and intestinal inflammation and residual beta cell function.

Подробное описание

The investigators perform a double-blind, randomized, placebo-controlled trial with two arms (10 participants per arm, total of 20 participants) in adults with longstanding type 1 diabetes with residual beta cell function. The study duration is 6 weeks, with 4 weeks of intervention in which participants will be given D. piger or placebo once daily and 2 weeks of washout period. The main study enpoints include the changes (versus baseline) in parameters of systemic/intestinal inflammation and beta cell function between the placebo and D.piger-treatment arms at the end of treatment (4 weeks). In addition, any long-lasting effects will be determined by assessing the changes in the above described markers after a 2 week washout period (6 weeks).

Secondary endpoints include glucose variability (continuous glucose monitoring, CGM), fecal microbiome composition (including strain engraftment of D. piger, plasma metabolites), immune cell phenotype and frequency and validated questionnaires (gastro-intestinal complaints) at these three timepoints (0,4,6 weeks).

Вмешательства

• Пищевая добавка Probiotic dietary supplement
  Probiotic bacteria D. piger (10\^9 colony forming units (CFU) in 10ml PBS containing 10% glycerol and 10% maltodextrin)
• Пищевая добавка Placebo
  Placebo (10ml PBS containing 10% glycerol and 10% maltodextrin)

Первичные конечные точки

• Parameters of systemic and intestinal inflammation [Срок оценки: From start treatment to the end of treatment at 4 weeks and washout at 6 weeks.]
• Residual beta cell function [Срок оценки: From start treatment to the end of treatment at 4 weeks and washout at 6 weeks.]

Вторичные конечные точки (4)

• Glucose variability [Срок оценки: From start treatment to the end of treatment at 4 weeks and washout at 6 weeks.]
• Immune cell phenotypes and frequency [Срок оценки: From start treatment to the end of treatment at 4 weeks and washout at 6 weeks.]
• Fecal microbiome composition and strain engraftment [Срок оценки: From start treatment to the end of treatment at 4 weeks and washout at 6 weeks.]
• Gastrointestinal Symptom Rating Scale (GSRS) [Срок оценки: From start treatment to the end of treatment at 4 weeks and washout at 6 weeks.]

Критерии участия

Критерии включения

• Males or females, age >18 years
• A diagnosis of type 1 diabetes, with duration of more than 5 years, with minimally one of antiGAD65, IA2, ZnT8 autoantibodies present assessed at diagnosis or routine visits at Diabeter Centrum.
• Evidence of remaining residual beta cell function with detectable UCPCR (more than 0.01 nmol/mmol C-peptide/creatinine ratio) and or fasting plasma C-peptide more than 0.2 mmol/L.
• BMI 18-30 kg/m2

Критерии исключения

• Use of antibiotics or proton-pump inhibitors within the last three months before screening or during study period
• Use of other probiotic supplementation within the last month before screening or during study period
• A history of cholecystectomy
• Overt untreated gastrointestinal disease, inflammatory bowel disease or abnormal bowel habits
• Absence of a large bowel (ie colostomy)
• Evidence for comprised immunity (HIV infection, chemotherapy, other autoimmune diseases, systemic anti-inflammatory therapy)
• History of cardiovascular disaeses (CVD) events
• Hepatic enzymes>2.5 higher than the upper limit of normal range, determined during MARVEL visits/routine visits
• Kidney failure (eGFR <15ml.min/1.73m2), dialysis, kidney transplantation,
• Inability or unwillingness to donate feces or urine.
• Smoking or illicit drug use (e.g. MDMA/amphetamine/cocaine/heroin/GHB) in the past three months or use during the study period.
• Alcohol abuse (equal or above 21 units per week)
• Inability or unwillingness to provide informed consent.

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

Лечение

Центры проведения

Нидерланды · 2 центра

• Diabeter Centrum Amsterdam — Amsterdam
• Amsterdam UMC — Amsterdam

Идентификаторы

NCT: NCT07585994 · 2025.1139

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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