CB5: Adipose Tissue Storage in the Rapid Remission of Hepatic and Cardiac Metabolic Dysfunction After Bariatric Surgery

Sponsor

Université de Sherbrooke (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05934409

Collaborator

Institut universitaire de cardiologie et de pneumologie de Québec, University Laval (Other), Centre de recherche du Centre hospitalier universitaire de Sherbrooke (Other)

Enrollment

Location

Arms

Anticipated Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus Type 2	Procedure: Bariatric surgery Drug: Nicotinic Acid	N/A

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

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.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.

Masking:

None (Open Label)

Primary Purpose:

Basic Science

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

Anticipated Study Start Date :

Sep 1, 2023

Anticipated Primary Completion Date :

Jan 31, 2028

Anticipated Study Completion Date :

May 1, 2028

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Control group without T2D according to Diabetes Canada diagnostics criteria:	Procedure: Bariatric surgery Laparoscopic Sleeve Gastrectomy Drug: Nicotinic Acid Only during A1. 150mg every half hour for 6 hours. A total dose of 1800mg will be ingested. Other Names: Niacin
Experimental: group with Type 2 diabetes with T2D according to Diabetes Canada diagnostics criteria:	Procedure: Bariatric surgery Laparoscopic Sleeve Gastrectomy Drug: Nicotinic Acid Only during A1. 150mg every half hour for 6 hours. A total dose of 1800mg will be ingested. Other Names: Niacin

Arm

Intervention/Treatment

Active Comparator: Control group

without T2D according to Diabetes Canada diagnostics criteria:

Procedure: Bariatric surgery

Laparoscopic Sleeve Gastrectomy

Drug: Nicotinic Acid

Only during A1. 150mg every half hour for 6 hours. A total dose of 1800mg will be ingested.

Other Names:

Niacin

Experimental: group with Type 2 diabetes

with T2D according to Diabetes Canada diagnostics criteria:

Procedure: Bariatric surgery

Laparoscopic Sleeve Gastrectomy

Drug: Nicotinic Acid

Only during A1. 150mg every half hour for 6 hours. A total dose of 1800mg will be ingested.

Other Names:

Niacin

Outcome Measures

Primary Outcome Measures

Change in white adipose tissue dietary fatty acid (DFA) trapping and partitioning [measured after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)]
[18F]-FTHA PET
Change in lean organ (liver, heart and muscle) DFA uptake and partitioning [measured after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)]
[18F]-FTHA PET
Change in liver non-esterified fatty acid (NEFA) uptake, oxidation, esterification and secretion into very low-density lipoprotein (VLDL). [measured before and after liquid meal at Baseline (A0), at Day 12 (B0) and at Week 52 (C0)]
calculated from the same multicompartmental equation using liver [11C]-palmitate kinetics
Change in Endogenous Glucose production and meal glucose systemic flux [measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)]
i.v. and oral stable isotope tracer
Change in cardiac non-esterified fatty acid (NEFA) uptake, oxidation and esterification [measured before and after liquid meal at Baseline (A0), at Day 12 (B0) and at Week 52 (C0)]
calculated from the same multicompartmental equation using cardiac [11C]-palmitate kinetics

Secondary Outcome Measures

Change in plasma NEFA flux [measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)]
calculated from i.v. stable isotope tracer (mass spectrometry).
Change in hepatic Triglyceride (TG) content [measured at Baseline (A0), at Day 12 (B0) and at Week 52 (C0)]
magnetic resonance imaging (MRI)
Change in insulin secretion [measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)]
Determined by measuring C-peptide kinetics following the liquid meal
Change in total substrate utilisation [measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)]
measured by using indirect calorimetry
Change in gene and protein expression of white adipose tissue (WAT) [measured at Baseline (A0), at Day 12 (B0) and at Week 52 (C0)]
WAT biopsy
Change in hormonal response [measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)]
Multiplex assay
Change in insulin resistance /sensitivity [measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)]
Determined by measuring circulating glucose, NEFA and insulin following the liquid meal
Change in histology of white adipose tissue (WAT) [measured at Baseline (A0), at Day 12 (B0) and at Week 52 (C0)]
WAT biopsy
Change in metabolite response [measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0]
Colorimetric assay
Change in plasma distribution of DFA metabolites (WAT DFA spillover) [measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)]
calculated from i.v. and oral stable isotope tracers (mass spectrometry) incorporated into triglyceride-rich lipoproteins and NEFA.
Change in glycerol turnover [measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)]
calculated from [1,1,2,3,3-2H]-glycerol i.v.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	centre de recherche du CHUS	Sherbrooke	Quebec	Canada	J1H 5N4

Sponsors and Collaborators

Université de Sherbrooke
Institut universitaire de cardiologie et de pneumologie de Québec, University Laval
Centre de recherche du Centre hospitalier universitaire de Sherbrooke