Clinical trial NCT05934409: Adipose Tissue Storage in the Rapid Remission of Hepatic and Cardiac Metabolic Dysfunction After Bariatric Surgery
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Diabetes Mellitus Type 2
Keywords: Bariatric surgery
remission from Type 2 diabetes
PET imaging
adipose tissue
Lead sponsor: Université de Sherbrooke
Sponsor class: OTHER
Collaborators: name: Institut universitaire de cardiologie et de pneumologie de Québec, University Laval
name: Centre de recherche du Centre hospitalier universitaire de Sherbrooke
First posted: 2023-07-07
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: It will be a randomized crossover study prior to bariatric surgery (visits A0 and A1) followed by a longitudinal follow-up study after surgery (visits B0 and C0) in two groups (type 2 diabetes vs. controls). Inside each group, the protocol will be carried out as a within-subject, in which each subject will serve as his/her own control.
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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

Primary outcomes:
measure: Change in white adipose tissue dietary fatty acid (DFA) trapping and partitioning
timeFrame: measured after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)
measure: Change in lean organ (liver, heart and muscle) DFA uptake and partitioning
timeFrame: measured after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)
measure: Change in liver non-esterified fatty acid (NEFA) uptake, oxidation, esterification and secretion into very low-density lipoprotein (VLDL).
timeFrame: measured before and after liquid meal at Baseline (A0), at Day 12 (B0) and at Week 52 (C0)
measure: Change in Endogenous Glucose production and meal glucose systemic flux
timeFrame: measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)
measure: Change in cardiac non-esterified fatty acid (NEFA) uptake, oxidation and esterification
timeFrame: measured before and after liquid meal at Baseline (A0), at Day 12 (B0) and at Week 52 (C0)
Secondary outcomes:
measure: Change in plasma NEFA flux
timeFrame: measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)
measure: Change in hepatic Triglyceride (TG) content
timeFrame: measured at Baseline (A0), at Day 12 (B0) and at Week 52 (C0)
measure: Change in insulin secretion
timeFrame: measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)
measure: Change in total substrate utilisation
timeFrame: measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)
measure: Change in gene and protein expression of white adipose tissue (WAT)
timeFrame: measured at Baseline (A0), at Day 12 (B0) and at Week 52 (C0)
measure: Change in hormonal response
timeFrame: measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)
measure: Change in insulin resistance /sensitivity
timeFrame: measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)
measure: Change in histology of white adipose tissue (WAT)
timeFrame: measured at Baseline (A0), at Day 12 (B0) and at Week 52 (C0)
measure: Change in metabolite response
timeFrame: measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0
measure: Change in plasma distribution of DFA metabolites (WAT DFA spillover)
timeFrame: measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)
measure: Change in glycerol turnover
timeFrame: measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)
Other outcomes:
Locations:
city: Sherbrooke
country: Canada
facility: centre de recherche du CHUS
state: Quebec
Study officials:
affiliation: Université de Sherbrooke
name: André Carpentier, MD
role: PRINCIPAL_INVESTIGATOR
References: