Glucose and Glycogen Dynamics in Prediabetes

NCT06317142 | Recruiting

• 1 other identifier: NL84574.068.23
• Study Type: observational
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this observational study is to investigate changes in nocturnal and postprandial glucose and glycogen metabolism in individuals with impaired fasting glucose and impaired glucose tolerance compared to healthy, non-diabetic, overweight participants (15 per group). In addition, it will be investigated if reducing gluconeogenesis, by using the challenge agent Acipimox, in people with prediabetes can increase glucose tolerance and fat oxidation by increased reliance on hepatic glycogen. The main questions this project aims to answer are:

• whether there are differences in nocturnal glucose/glycogen metabolism in individuals with impaired fasting glucose, impaired glucose tolerance and healthy overweight controls.
• whether there are differences in postprandial glucose/glycogen metabolism in individuals with impaired fasting glucose, impaired glucose tolerance and healthy overweight controls. Participants will visit the university for a screening visit and a visit with overnight stay for measurements of gluconeogenesis, glycogen, and substrate oxidation. A subgroup will receive \[18F\]-FDG to assess tissue-specific postprandial glucose uptake. Thereafter, 20 prediabetic individuals will follow a 4-day treatment with acipimox to decrease gluconeogenesis, followed by a second overnight visit with similar measurements as mentioned for the first visit.

Conditions

Pre Diabetes

Outcome Measures

Primary Outcomes (3)

• Hepatic and muscle glycogen measured by 13Carbon-Magnetic resonance spectroscopy (13C-MRS)

  Difference in overnight and postprandial change of hepatic and muscle glycogen measured by 13C-MRS between healthy overweight volunteers and volunteers with IFG and IGT

  During day 1 and day 2

• Whole body gluconeogenesis determined by deuterated water

  Difference in whole-body gluconeogenesis between healthy overweight volunteers and IFG and IGT volunteers

  During day 1 and day 2

• Postprandial hepatic and muscle glucose uptake determined by Fluorodeoxyglucose-Positron emission tomography ([18F]-FDG-PET) combined with oral glucose tolerance test (OGTT)

  Difference in glucose uptake between healthy overweight volunteers and IFG and IGT volunteers

  During day 2

Secondary Outcomes (3)

• Oral glucose tolerance after acipimox treatment measured by OGTT

  During day 2 and day 6

• Hepatic glycogen after acipimox treatment measured by 13C-MRS

  During day 1,2, 5 and 6

• Whole body gluconeogenesis after acipimox treatment determined by deuterated water

  During day 1,2, 5 and 6

Other Outcomes (5)

• Hepatic acetylcarnitine as a measure for hepatic gluconeogenesis determined by H-MRS

  During day 1,2, 5 and 6

• Substrate oxidation (fat and carbohydrate oxidation) determined by indirect calorimetry

  During day 1,2, 5 and 6

• Dynamic water relaxation measurements with 1H-MRS (surrogate glycogen)

  During day 1,2, 5 and 6

Study Arms (3)

Healthy overweight volunteers

This group includes 15 healthy overweight volunteers. These participants will undergo two test days with one overnight stay. During these days several tests will be conducted including measurements such as muscle and liver glycogen, whole-body gluconeogenesis, substrate oxidation and postprandial hepatic and muscle glucose uptake will be assessed by 18F-FDG PET combined with an oral glucose tolerance test.

Prediabetes volunteers-IFG

This group will include 15 subjects with impaired fasting glucose (IFG). These participants will undergo two test days with one overnight stay. During these days several tests will be conducted including measurements such as muscle and liver glycogen, whole-body gluconeogenesis, substrate oxidation and postprandial hepatic and muscle glucose uptake will be assessed by 18F-FDG PET combined with an oral glucose tolerance test. A subset of IFG prediabetes individuals with impaired fasting glucose (first 10 subjects enrolled) will receive a 4-day Acipimox treatment (3x 250mg capsules for three days (one with breakfast, one with lunch and one with snack) and 1x 250mg in the morning of day 4. After the intervention the participants will come to the university for two days with an overnight stay for tests (muscle and liver glycogen, whole-body gluconeogenesis, substrate oxidation, oral glucose tolerance test).

Drug: Acipimox 250 mg Oral Capsule

Prediabetes volunteers-IGT

This group will include 15 subjects with impaired glucose tolerance (IGT). These participants will undergo two test days with one overnight stay. During these days several tests will be conducted including measurements such as muscle and liver glycogen, whole-body gluconeogenesis, substrate oxidation and postprandial hepatic and muscle glucose uptake will be assessed by 18F-FDG PET combined with an oral glucose tolerance test. A subset of IGT prediabetes individuals with impaired fasting glucose (first 10 subjects enrolled) will receive a 4-day Acipimox treatment (3x 250mg capsules for three days (one with breakfast, one with lunch and one with snack) and 1x 250mg in the morning of day 4. After the intervention the participants will come to the university for two days with an overnight stay for tests (muscle and liver glycogen, whole-body gluconeogenesis, substrate oxidation, oral glucose tolerance test).

Drug: Acipimox 250 mg Oral Capsule

Interventions

Acipimox 250 mg Oral Capsule DRUG

A subset of prediabetes individuals (first 10 IFG and 10 IGT subjects enrolled) will receive a 4-day Acipimox treatment (3x 250mg capsules for three days (one with breakfast,one with lunch and one with snack) and 1x 250mg in the morning of day 4.

Also known as: Olbetam 250 mg oral capsule

Prediabetes volunteers-IFG; Prediabetes volunteers-IGT

Eligibility Criteria

• Age: 45 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

15 healthy overweight participants, 15 participants with prediabetes characterised by IGT and 15 participants with prediabetes characterised by IFG. All participants will be aged 45-75y, with a BMI between 27-38 kg/m2, stable dietary habets, a sedentary lifestyle and no sign of active disease or excesive alcohol consumption.

You may qualify if:

• Participants are able to provide signed and dated written informed consent prior to any study specific procedures
• Participants should have suitable veins for cannulation or repeated venipuncture
• Women are post-menopausal (defined as at least 1 year post cessation of menses)
• Aged ≥ 45 and ≤ 75 years
• Body mass index (BMI) 27 - 38 kg/m2
• Stable dietary habits (no weight loss or gain \>5kg in the past 3 months)
• Sedentary lifestyle (not more than 2 hours of sports per week)
• Impaired Fasting Glucose: fasting blood glucose between 6.1 and 6.9 mmol/L and 2-h plasma glucose after ingestion of 75g oral glucose load below 7.8 mmol/L Impaired Glucose Tolerance: fasting blood glucose below 6.1 mmol/L and 2-h plasma glucose after ingestion of 75g oral glucose load between 7.8 and 11.1 mmol/L

You may not qualify if:

• Previous enrolment in a clinical study with an investigational product during the last 3 months or as judged by the Investigator
• Previously diagnosed with type 2 diabetes
• Patients with congestive heart failure and/or severe renal (eGFR \<50mL/min) and or liver insufficiency or another condition that may interfere with outcomes measured in this study.
• Any contra-indication MRI scanning
• Alcohol consumption of \>2 servings per day for men and \>1 servings per day for woman
• Smoking in the past 6 months
• Medication use that may influence main outcome parameters, specifically the following types of medication: Type 2 diabetes medication, corticosteroids, thyroid medication.
• Participation in research or medical examination that included PET scanning in the last 3 months
• \- Any of the criteria mentioned above to define prediabetes
• Gout
• Hypersensitivity to acipimox or to any of the excipients in the tablet
• Peptic ulcer/dyspepsia
• Medication that interferes with Acipimox (statins, fibrates).

Sponsors & Collaborators

• Maastricht University Medical Center: lead

Study Sites (1)

Maastricht University

Maastricht, Limburg, 6229ER, Netherlands

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Plasma samples

MeSH Terms

Conditions

Glucose Intolerance

Interventions

acipimox

Condition Hierarchy (Ancestors)

Hyperglycemia; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Vera Schrauwen, PhD

  Maastricht University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kay Roumans, PhD

CONTACT

+31433882124; k.roumans@maastrichtuniversity.nl

Mijke Buitinga, PhD

CONTACT

+31883887286; m.buitinga@maastrichtuniversity.nl

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2023
• First Posted: March 19, 2024
• Study Start: February 20, 2024
• Primary Completion: July 1, 2025
• Study Completion: July 1, 2025
• Last Updated: April 9, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)