Adipose Tissue Storage in the Rapid Remission of Hepatic and Cardiac Metabolic Dysfunction After Bariatric Surgery

Официальное название

Improved Adipose Tissue Storage of Dietary Fatty Acids as a New Mechanism for the Rapid Remission of Hepatic and Cardiac Metabolic Dysfunction After Bariatric Surgery

Обзор

The present protocol aims to understand and establish whether there is a causal link between adipose tissue metabolic remodeling and Type 2 Diabetes (T2D) remission after bariatric surgery. All participants will have a bariatric surgery, divided in 2 groups: with or without T2D.

Подробное описание

This clinical assay will include 5 visits: the screening visit and four 9-hour postprandial metabolic sessions (A0, A1, B0 and C0) before and after surgery:

* initial visit: screening * before surgery: 2 metabolic sessions A0 and A1 (without/with niacin) will be performed, in random order, at least one week interval. * 12 days post surgery: 1 metabolic session B0 (without niacin) * 1 year post surgery: 1 metabolic session C0 (without niacin)

Each metabolic visit will last 9 hours with:

* perfusion of stable tracers, * ingestion of a liquid meal * Positron-Emitting-Tomography (PET) acquisitions using radiopharmaceuticals such as \[18F\]-fluoro-6-thia-heptadecanoic acid (\[18F\]-FTHA) and \[11C\]-palmitate, * MRI acquisitions.\[18F\]fluoro-6-thia-heptadecanoic acid (FTHA).

The niacin will be given during metabolic visits A1 as a regulator of lipids metabolism. During these visits, the subjects will ingest 150mg every half hour for 6 hours. Niacin will be used as a pharmacological suppressor of dietary fatty acid (DFA) spillover in order to determine the role played by this mechanism in the reduction of postprandial endogen glucose production (EGP) in T2D after bariatric surgery.

Вмешательства

• Процедура Bariatric surgery
  Laparoscopic Sleeve Gastrectomy
• Препарат Nicotinic Acid
  Only during A1. 150mg every half hour for 6 hours. A total dose of 1800mg will be ingested.

Первичные конечные точки

• Change in white adipose tissue dietary fatty acid (DFA) trapping and partitioning [Срок оценки: measured after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)]
• Change in lean organ (liver, heart and muscle) DFA uptake and partitioning [Срок оценки: measured after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)]
• Change in liver non-esterified fatty acid (NEFA) uptake, oxidation, esterification and secretion into very low-density lipoprotein (VLDL). [Срок оценки: measured before and after liquid meal at Baseline (A0), at Day 12 (B0) and at Week 52 (C0)]
• Change in Endogenous Glucose production and meal glucose systemic flux [Срок оценки: measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)]
• Change in cardiac non-esterified fatty acid (NEFA) uptake, oxidation and esterification [Срок оценки: measured before and after liquid meal at Baseline (A0), at Day 12 (B0) and at Week 52 (C0)]

Вторичные конечные точки (11)

• Change in plasma NEFA flux [Срок оценки: measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)]
• Change in hepatic Triglyceride (TG) content [Срок оценки: measured at Baseline (A0), at Day 12 (B0) and at Week 52 (C0)]
• Change in insulin secretion [Срок оценки: measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)]
• Change in total substrate utilisation [Срок оценки: measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)]
• Change in gene and protein expression of white adipose tissue (WAT) [Срок оценки: measured at Baseline (A0), at Day 12 (B0) and at Week 52 (C0)]
• Change in hormonal response [Срок оценки: measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)]
• Change in insulin resistance /sensitivity [Срок оценки: measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)]
• Change in histology of white adipose tissue (WAT) [Срок оценки: measured at Baseline (A0), at Day 12 (B0) and at Week 52 (C0)]
• Change in metabolite response [Срок оценки: measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0]
• Change in plasma distribution of DFA metabolites (WAT DFA spillover) [Срок оценки: measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)]
• Change in glycerol turnover [Срок оценки: measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)]

Критерии участия

Критерии включения

• Aged 18 to 65
• BMI 35 kg/m2
• Diagnosed T2D - according to Diabetes Canada diagnostics criteria.
• Diagnosed non-T2D - according to Diabetes Canada diagnostics criteria.
• Women with a negative serum pregnancy test.

Критерии исключения

• Treatment with an oral contraceptive;
• Treatment with fibrate, thiazolidinedione, insulin, or beta-blocker, drugs that affect metabolism and cannot be stopped temporarily or which have long-lasting effects;
• Presence of overt cardiovascular disease, liver or renal failure or other uncontrolled medical conditions;
• Any other contraindication to surgery or to temporarily suspending current medications for diabetes, lipids or hypertension;
• Smoking or consumption of more than 2 alcoholic beverages per day;
• Any contraindication to MRI;
• A Diabetes Remission (DiaRem) score >8 (low probability of T2D remission);
• Having participated to a research study with exposure to radiation in the last two years before the start of the study;
• Pregnant or breastfeeding women;
• Patients weighing more than 200 kg to respect the weight and gantry limit of our MRI and PET/CT scanners.
• Being allergic to eggs

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

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Фундаментальное исследование

Центры проведения

Канада · 1 центр

• centre de recherche du CHUS — Sherbrooke

Идентификаторы

NCT: NCT05934409 · 2022-4624

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗