Glucose and Glycogen Dynamics in Prediabetes

Pre Diabetes Clinical Trial

— GGD  

Official title:

Investigating Disturbances in Glucose and Glycogen Dynamics in Prediabetes

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06317142
• Other study ID #: NL84574.068.23
• Status: Recruiting
• Start date: February 20, 2024
• Est. completion date: July 2025

Study information

• Verified date: March 2024
• Source: Maastricht University Medical Center
• Contact: Kay Roumans, PhD
• Phone: +31433882124
• Email: k.roumans[@]maastrichtuniversity.nl
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 45
• Est. completion date: July 2025
• Est. primary completion date: July 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 45 Years to 75 Years

Eligibility

Inclusion Criteria for all groups:

• 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)

Inclusion Criteria for Prediabetic groups specifically:

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

Exclusion Criteria for all groups:

• 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

Exclusion Criteria for Healthy overweight specifically:

• Any of the criteria mentioned above to define prediabetes

Exclusion Criteria for Prediabetic groups who will undergo acipimox treatment:

• Gout

• Hypersensitivity to acipimox or to any of the excipients in the tablet

• Peptic ulcer/dyspepsia

• Medication that interferes with Acipimox (statins, fibrates).

Related Conditions & MeSH terms

• Pre Diabetes
• Prediabetic State

Intervention

Drug:
• Acipimox 250 mg Oral Capsule
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.

Locations

Country	Name	City	State
Netherlands	Maastricht University	Maastricht	Limburg

Sponsors (1)

Lead Sponsor	Collaborator
Maastricht University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Hepatic acetylcarnitine as a measure for hepatic gluconeogenesis determined by H-MRS	Difference in hepatic acetylcarnitine between healthy overweight volunteers and individuals with IGT and IFG and the difference in hepatic acetylcarnitine before and after 4 days of acipimox treatment in prediabetic volunteers (intra- and inter-group comparisons).	During day 1,2, 5 and 6
Other	Substrate oxidation (fat and carbohydrate oxidation) determined by indirect calorimetry	Difference in substrate oxidation (fat and carbohydrate oxidation) between healthy overweight volunteers and IFG and IGT volunteers and the difference in substrate oxidation before and after 4 days of acipimox treatment in IFG and IGT volunteers (intra- and inter-group comparisons).	During day 1,2, 5 and 6
Other	Dynamic water relaxation measurements with 1H-MRS (surrogate glycogen)	Difference in water relaxation measures between healthy overweight volunteers and IFG and IGT volunteers.	During day 1,2, 5 and 6
Other	Anthropometric measurements	weight and height will be combined to report BMI in kg/m^2 (to characterize participants)	During the screening day
Other	Body composition determined by Bodpod	fat mass and fat free mass as % (to characterize participants)	During day 1
Primary	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
Primary	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
Primary	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	Oral glucose tolerance after acipimox treatment measured by OGTT	Difference in glucose tolerance measured by OGTT before and after 4 days of acipimox treatment in prediabetic volunteers (intra- and inter-group comparisons)	During day 2 and day 6
Secondary	Hepatic glycogen after acipimox treatment measured by 13C-MRS	Difference in overnight change of hepatic glycogen before and after 4 days of acipimox treatment in prediabetic volunteers (intra- and inter-group comparisons)	During day 1,2, 5 and 6
Secondary	Whole body gluconeogenesis after acipimox treatment determined by deuterated water	Difference in whole body gluconeogenesis before and after 4 days of acipimox treatment in prediabetic volunteers (intra- and inter-group comparisons)	During day 1,2, 5 and 6