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

Diabetes Mellitus Type 2 Clinical Trial

— CB5  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05934409
• Other study ID #: 2022-4624
• Status: Recruiting
• Phase: N/A
• Start date: November 1, 2023
• Est. completion date: May 1, 2028

Study information

• Verified date: November 2023
• Source: Université de Sherbrooke
• Contact: Frédérique Frisch
• Phone: 1-819-346-1110
• Email: frederique.frisch[@]usherbrooke.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: May 1, 2028
• Est. primary completion date: January 31, 2028
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus Type 2
• Diabetes Mellitus, Type 2

Intervention

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.

Locations

Country	Name	City	State
Canada	centre de recherche du CHUS	Sherbrooke	Quebec

Sponsors (3)

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

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in white adipose tissue dietary fatty acid (DFA) trapping and partitioning	[18F]-FTHA PET	measured after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)
Primary	Change in lean organ (liver, heart and muscle) DFA uptake and partitioning	[18F]-FTHA PET	measured after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)
Primary	Change in liver non-esterified fatty acid (NEFA) uptake, oxidation, esterification and secretion into very low-density lipoprotein (VLDL).	calculated from the same multicompartmental equation using liver [11C]-palmitate kinetics	measured before and after liquid meal at Baseline (A0), at Day 12 (B0) and at Week 52 (C0)
Primary	Change in Endogenous Glucose production and meal glucose systemic flux	i.v. and oral stable isotope tracer	measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)
Primary	Change in cardiac non-esterified fatty acid (NEFA) uptake, oxidation and esterification	calculated from the same multicompartmental equation using cardiac [11C]-palmitate kinetics	measured before and after liquid meal at Baseline (A0), at Day 12 (B0) and at Week 52 (C0)
Secondary	Change in plasma NEFA flux	calculated from i.v. stable isotope tracer (mass spectrometry).	measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)
Secondary	Change in hepatic Triglyceride (TG) content	magnetic resonance imaging (MRI)	measured at Baseline (A0), at Day 12 (B0) and at Week 52 (C0)
Secondary	Change in insulin secretion	Determined by measuring C-peptide kinetics following the liquid meal	measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)
Secondary	Change in total substrate utilisation	measured by using indirect calorimetry	measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)
Secondary	Change in gene and protein expression of white adipose tissue (WAT)	WAT biopsy	measured at Baseline (A0), at Day 12 (B0) and at Week 52 (C0)
Secondary	Change in hormonal response	Multiplex assay	measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)
Secondary	Change in insulin resistance /sensitivity	Determined by measuring circulating glucose, NEFA and insulin following the liquid meal	measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)
Secondary	Change in histology of white adipose tissue (WAT)	WAT biopsy	measured at Baseline (A0), at Day 12 (B0) and at Week 52 (C0)
Secondary	Change in metabolite response	Colorimetric assay	measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0
Secondary	Change in plasma distribution of DFA metabolites (WAT DFA spillover)	calculated from i.v. and oral stable isotope tracers (mass spectrometry) incorporated into triglyceride-rich lipoproteins and NEFA.	measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)
Secondary	Change in glycerol turnover	calculated from [1,1,2,3,3-2H]-glycerol i.v.	measured before and after liquid meal at Baseline (A0 +A1), at Day 12 (B0) and at Week 52 (C0)