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Impaired Glucose ToleranceAGL11NCT02808182

Postprandial Fatty Acid Metabolism in the Natural History of Type 2 Diabetes (T2D)

A study testing Nicotinic acid, [7,7,8,8-2H]-palmitate and [U-13C]-palmitate in people with Impaired Glucose Tolerance, run by Université de Sherbrooke at 1 site in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Lipotoxicity-causing fatty acid overexposure and accretion in lean tissues leads to insulin resistance and impaired pancreatic β-cell function - the hallmarks of T2D - contributing to associated complications such as heart failure, kidney failure and microvascular diseases. Read more about this study

Who is it for?
Ages 45 to 80 yearsHealthy volunteers can take part
Conditions the study is for
Impaired Glucose Tolerance
What is being tested?
Nicotinic acid, [7,7,8,8-2H]-palmitate and [U-13C]-palmitate
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
1 siteCanada
Study dates
17 Jan 2017to May 2021
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 45 to 80 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • For healthy subjects: fasting glucose < 5.6, 2-hour post 75g Oral Glucose Tolerance Test (OGTT) glucose < 7.8 mmol/l and HbA1c < 5.8%
  • For subject with glucose intolerance (IGT): 2-hour post 75g OGTT glucose at 7.8-11.1 mmol/l on two separate occasions and HbA1c of 6.0 to 6.4%

Who cannot join

  • overt cardiovascular disease as assessed by medical history, physical exam, and abnormal ECG
  • treatment with a fibrate, thiazolidinedione, beta-blocker or other drug known to affect lipid or carbohydrate metabolism (except statins, metformin, and other antihypertensive agents that can be safely interrupted)
  • presence of liver or renal disease, uncontrolled thyroid disorder, previous pancreatitis, bleeding disorder, or other major illness
  • smoking (>1 cigarette/day) and/or consumption of >2 alcoholic beverages per day
  • prior history or current fasting plasma cholesterol level > 7 mmol/l or fasting TG > 6 mmol/l
  • any other contraindication to temporarily interrupt current meds for lipids or hypertension
  • being pregnant
  • not be barren

Trial locations and contacts

1 site in 1 country.

Canada1 site
  • centre de recherche du CHUS

    Sherbrooke, Quebec, J1H 5N4

Other trials in Canada

About this study

Official title: Postprandial Fatty Acid Metabolism in the Natural History of Type 2 Diabetes (T2D): Relative Contribution of Dietary vs Systemic Fatty Acids to Lean Tissue Fatty Acid Fluxes and Oxidative vs Non-oxidative Pathways

Lipotoxicity-causing fatty acid overexposure and accretion in lean tissues leads to insulin resistance and impaired pancreatic β-cell function - the hallmarks of T2D - contributing to associated complications such as heart failure, kidney failure and microvascular diseases. Proper dietary fatty acid (DFA) storage in white adipose tissue (WAT) is now thought to prevent lean-tissue lipotoxicity. Using novel Positron-Emission Tomography (PET) and stable isotopic tracer methods which were developed in Sherbrooke, the investigator showed that WAT storage of DFA is impaired in people with pre-diabetes or T2D. The investigator also showed that this impairment is associated with greater cardiac DFA uptake, as well as subclinical left-ventricular systolic and diastolic dysfunction. Then, It has been found that modest weight loss in pre-diabetics, after a one-year lifestyle intervention, improved WAT DFA storage, curbed cardiac DFA uptake, and restored associated left-ventricular dysfunction. It has been also found that a 7-day low-saturated fat, low-calorie diet raised insulin sensitivity but did not restore WAT or cardiac DFA metabolism. Whether WAT DFA storage directly impacts cardiac DFA uptake is not known. Importantly, the investigator recently uncovered marked sex-specific differences in WAT DFA metabolism. These may explain, at least in part, sex-related differences in the cardiac DFA uptake, which occurs in pre-diabetes. Higher spillover of WAT DFA into circulating Non-Esterified Fatty Acid (NEFA) appears to be linked in women to greater cardiac DFA uptake, as opposed to direct cardiac chylomicron triglycerides (TG) uptake in men. Here, the investigator will isolate and compare organ-specific fatty acid uptake occurring postprandially from chylomicron-TG vs. NEFA pools, as well as the oxidative vs. non-oxidative intracellular metabolic pathways associated with increased cardiac DFA uptake in pre-diabetic men and women.

Being tested
Nicotinic acid, [7,7,8,8-2H]-palmitate, [U-13C]-palmitate, Biopsy, liquid meal
Medical subject headings
Glucose Intolerance

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Nicotinic acidDrug

    Also called Niacin

    oral administration of nicotinic acid (100mg at 0, 30, 60, 90, 120, 180, 240 and 300 min) to minimize WAT intracellular lipolysis

  • [7,7,8,8-2H]-palmitateOther

    using i.v. administration of [7,7,8,8-2H]-palmitate (in 25% human albumin) from time -60 to +360 min

  • [U-13C]-palmitateOther

    oral administration of [U-13C]-palmitate (0.2 g mixed into the liquid meal) at time 0 min

  • BiopsyProcedure or surgery

    A subcutaneous abdominal 0.5-g adipose tissue biopsy will be performed at the end of protocols A0 and A1

  • liquid mealOther

    At time 0, a standard liquid meal (400 mL, 906 kcal, 33g-fat/34g-protein/101g-carbohydrates i.e. 33%/17%/50% calories) will be drunk over 20 minutes

Study groups in NCT02808182
Study groupRoleWhat they receive
A0: PET/scan with [11C] palmitateOtherA bolus of 180 MBq of [11C]-acetate at time 90min and PET acquisition
Receives: Procedure: Biopsy; Other: liquid meal
A1: PET/scan with [11C] palmitateOtherA bolus injection of 180 MBq of [11C]-acetate at time 90min, followed by PET acquisition
Receives: Drug: Nicotinic acid; Procedure: Biopsy; Other: liquid meal
B0: PET/scan with [18F]-FTHAOtherAt time 0, a standard liquid meal will be drunk over 20 minutes with 70 MBq of 18FTHA . PET acquisition at time 90 min.
Receives: Other: [7,7,8,8-2H]-palmitate; Other: [U-13C]-palmitate; Other: liquid meal
B1: PET/scan with [18F]-FTHAOtherAt time 0, a standard liquid meal will be drunk over 20 minutes with 70 MBq of 18FTHA followed by a PET acquisition at time 90 min.
Receives: Drug: Nicotinic acid; Other: [7,7,8,8-2H]-palmitate; Other: [U-13C]-palmitate; Other: liquid meal

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Plasma NEFA appearance rate

    NEFA appearance will be measured using i.v. administration of [7,7,8,8-2H]-palmitate (in 25% human albumin) from time -60 to +360 min, as slightly modified from previous descriptions, using Steele's non steady-state equations. Blood samples to measure plasma palmitate, oleate, linoleate, and total NEFA levels, [7,7,8,8-2H]-palmitate enrichments by GC/MS-MS.

    Measured: 2 years

  2. Cardiac and hepatic uptake

    will be determined using 11C-palmitate PET/CT. 180 MBq will be administered by bolus injection at postprandial time 90min. After a transmission scan and regional CT (40mA), a 30-min dynamic list-mode PET acquisition will be performed starting at time 90 min on a 18 cm-high thoraco-abdominal segment to include the left cardiac ventricle and most of the liver on a Philips Gemini TOF PET/CT

    Measured: 2 years

  3. WAT spillover NEFA appearance rates

    WAT spillover NEFA will be determined from oral administration of [U-13C]-palmitate.

    Blood samples to measure plasma [U-13C]-palmitate and chylomicron-TG [U-13C]-palmitate enrichment by GC/MS-MS

    Measured: 2 years

  4. oxidative metabolism of NEFA

    will be assessed by using 13C-palmitate

    Measured: 2 years

  5. cardiac and hepatic DFA uptake

    will be assessed using PET/CT method with oral administration of 18FTHA

    Measured: 2 years

  6. whole-body organ-specific DFA partitioning

    will be determined by whole-body CT (16 mA) followed by PET acquisition of 18FTHA

    Measured: 2 years

Secondary outcomes (6)
  1. Insulin sensitivity

    will be determined using the HOMA-IR (based on fasting insulin and glucose levels)

    Measured: 2 years

  2. Insulin secretion rate

    will be assessed using deconvolution of plasma C-peptide with standard C-peptide kinetic parameters

    Measured: 2 years

  3. β-cell function

    will be assessed by calculation of the disposition index (DI) that is insulin secretion in response to the ambient insulin

    Measured: 2 years

  4. WAT size

    by biopsy fixed in formalin

    Measured: 2 years

  5. hormonal response

    will be determined using a multiplex assay system

    Measured: 2 years

  6. Lipoprotein lipase activity

    will be assessed as on frozen 150-mg portions from biopsy

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Jun 2016 (estimated)
  2. Study start17 Jan 2017
  3. Primary completionDec 2020
  4. Study completionMay 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
50 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02808182
Sponsor's protocol ID
2016-1196
Acronym
AGL11
Status last verified
Jan 2025
First submitted
14 Apr 2016
Last updated
27 Jan 2025
Results posted
No

Publications

  • Montastier E, Ye RZ, Noll C, Amrani M, Frisch F, Fortin M, Bouffard L, Phoenix S, Sarrhini O, Cunnane SC, Guerin B, Turcotte EE, Carpentier AC. Nicotinic acid increases adipose tissue dietary fatty acid trapping and reduces postprandial hepatic and cardiac fatty acid uptake in prediabetes. Eur J Pharmacol. 2025 Jul 5;998:177563. doi: 10.1016/j.ejphar.2025.177563. Epub 2025 Mar 27.

    PubMed 40157702
  • Ye RZ, Montastier E, Noll C, Frisch F, Fortin M, Bouffard L, Phoenix S, Guerin B, Turcotte EE, Carpentier AC. Total Postprandial Hepatic Nonesterified and Dietary Fatty Acid Uptake Is Increased and Insufficiently Curbed by Adipose Tissue Fatty Acid Trapping in Prediabetes With Overweight. Diabetes. 2022 Sep 1;71(9):1891-1901. doi: 10.2337/db21-1097.

    PubMed 35748318
  • Montastier E, Ye RZ, Noll C, Bouffard L, Fortin M, Frisch F, Phoenix S, Guerin B, Turcotte EE, Lewis GF, Carpentier AC. Increased postprandial nonesterified fatty acid efflux from adipose tissue in prediabetes is offset by enhanced dietary fatty acid adipose trapping. Am J Physiol Endocrinol Metab. 2021 Jun 1;320(6):E1093-E1106. doi: 10.1152/ajpendo.00619.2020. Epub 2021 Apr 19.

    PubMed 33870714

Questions about this trial

What is this clinical trial studying?

A study testing Nicotinic acid, [7,7,8,8-2H]-palmitate and [U-13C]-palmitate in people with Impaired Glucose Tolerance, run by Université de Sherbrooke at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Plasma NEFA appearance rate (time frame: 2 years). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02808182, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jan 2025.

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