Fiber and Metformin Combination Therapy in Adolescents With Severe Obesity and Insulin Resistance

Официальное название

Fiber Supplementation and Metformin Combination Therapy in Adolescents With Severe Obesity and Insulin Resistance: Interactions With the Gut Microbiome.

Обзор

This is a 12-month, single center, three-arm parallel design, double-blind, randomized clinical trial, to compare the effects of supplemental dietary fiber and metformin (MET) alone and in combination over 12 months on glucose metabolism (insulin resistance \[IR\]), inflammation and BMI in adolescents with obesity and IR, and to assess the relationship between therapeutic intervention(s) and changes in gut microbiome composition and function. Since MET and FIBER have been shown to reduce weight and increase insulin sensitivity through distinct but overlapping mechanisms of action, our central hypothesis is that the combination of FIBER + MET will have a synergistic effect and be more effective than FIBER or MET alone in improving metabolic function (IR) and reducing BMI and inflammation in adolescents with obesity, IR and family history (FM) of T2DM. .

Вмешательства

• Препарат Metformin 850 mg oral tablet bid
  MET dose: 500 mg daily, increasing to 500 bid if tolerated after 2 weeks, then increasing again 2 weeks later to 850 mg bid (1700 mg daily).
• Пищевая добавка Supplemental fiber mixture (35 g total) composed of 6g of Oligofructose + 12g of resistant maltodextrin + 12g of acacia gum + 5g of PGX.
  The first week of treatment will use 1/3 the daily treatment dose; then 2/3 dose for the second and third weeks; then the full dose thereafter, to allow time for adaptation.

Первичные конечные точки

• Changes in HOMA-IR [Срок оценки: Baseline, 6, and 12 months]

Вторичные конечные точки (11)

• Changes in body weight [Срок оценки: Baseline, 6, and 12 months]
• Changes in body mass index (BMI) [Срок оценки: Baseline, 6, and 12 months]
• Changes in body composition [Срок оценки: Baseline, 6, and 12 months]
• Changes in inflammation [Срок оценки: Baseline, 6, and 12 months]
• Changes in metabolic function [Срок оценки: Baseline, 6, and 12 months]
• Changes in satiety hormones [Срок оценки: Baseline, 6, and 12 months]
• Changes in quality of life [Срок оценки: Baseline, 6, and 12 months]
• Changes in perceived hunger and satiety [Срок оценки: Baseline, 6, and 12 months]
• Changes in gut microbiota composition [Срок оценки: Baseline, 6, and 12 months]
• Changes in gut microbiome functions [Срок оценки: Baseline, 6, and 12 months]
• Changes in intestinal barrier integrity [Срок оценки: Baseline, 6, and 12 months]

Критерии участия

Критерии включения

• Age 12-18 years
• BMI percentile > 95% for age/sex;
• Total weight fluctuation over past 6 months < 10%;
• HOMA-IR > 3.16;
• FH of T2DM (first or second-degree relative).

Критерии исключения

• Current use of insulin or diagnosis of T2DM;
• Systolic or diastolic blood pressure (BP) > 99th percentile for age and sex;
• Acute infectious or inflammatory condition over the preceding 1 month; hospitalization > 48 hrs;
• History of chronic disease such as inflammatory bowel disease, chronic severe liver or kidney disease or neurologic disorders;
• Active malignancy;
• Concomitant use of medication/investigational drug known to affect body weight in the past year;
• Antibiotic use in past 60 days; probiotic and/or prebiotic supplements use in the past 30 days; use of lipid-lowering and anti-inflammatory medication.

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

Лечение

Центры проведения

Канада · 1 центр

• University of Alberta — Edmonton

Публикации

• Fahim SM, Huey SL, Palma Molina XE, Agarwal N, Ridwan P, Ji N, Kibbee M, Kuriyan R, Finkelstein JL, Mehta S. Gut microbiome-based interventions for the management of obesity in children and adolescents aged up to 19 years. Cochrane Database Syst Rev. 2025 Jul 10;7(7):CD015875. doi: 10.1002/14651858.CD015875. PMID 40637175
• Deehan EC, Colin-Ramirez E, Triador L, Madsen KL, Prado CM, Field CJ, Ball GDC, Tan Q, Orsso C, Dinu I, Pakseresht M, Rubin D, Sharma AM, Tun H, Walter J, Newgard CB, Freemark M, Wine E, Haqq AM. Efficacy of metformin and fermentable fiber combination therapy in adolescents with severe obesity and insulin resistance: study protocol for a double-blind randomized controlled trial. Trials. 2021 Feb 1 PMID 33596993

Идентификаторы

NCT: NCT04578652 · RN. # 414120

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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