The TiMeD-T1D Project

NCT ID: NCT07172672

Last Updated: 2025-09-26

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-11-01
• Study Completion Date: 2027-11-01

Brief Summary

The aim of the proposed study is to investigate the metabolic consequences of varying the timing of meal insulin boluses and skipping boluses altogether in individuals with type 1 diabetes.

The investigator hypothesize that delaying or skipping meal insulin boluses leads to greater ectopic fat storage due to a delayed stimulation of lipoprotein activity and delayed suppression of lipolysis and VLDL-TG secretion.

Detailed Description

The study will be carried out as a randomized cross-over clinical investigational trial. The investigators will include 10 individuals with type 1 diabetes. The subjects will be invited for four visits in total: one screening visit and three test days separated by a one-week washout period. At the test days, subjects will consume a liquid mixed meal and: 1) take a meal bolus of insulin 20 min before consuming a liquid mixed meal or 2) take a meal bolus of insulin 20 min after the meal or 3) skip the meal bolus of insulin.

The investigators will apply the 18F-FTHA meal fat tracer method to the liquid mixed meal to determine whole-body organ-specific meal fat storage.

The volunteers will arrive fasted (8 hours) at the Department of Nuclear Medicine & PET-Centre at 9.00 a.m. Upon arrival, participants will be placed in a bed and have an arterial catheter placed for arterial blood sampling collected at baseline and during the entire trial day. Approximately one hour after arriving, participants will consume a liquid mixed meal consisting of 400 mL Fresubin Energy Drink and 100 mL heavy cream with the addition of the 18F-FTHA radiotracer. 5 hours after consumption of the liquid mixed meal one static whole-body PET-scan will be performed with a duration of 1 hours. After the PET-scan participants will be provided with a meal. Subsequently, the investigator will make sure the participants is metabolic corrected and then the trial day is ended, and they can go home.

The three test days will be conducted in the same way, except for the timing of insulin bolus administration relative to the meal, which will vary as follows:

1. Meal insulin bolus 20 min before consumption of a liquid mixed meal (as recommended)

2. Meal insulin bolus 20 min after consumption of a liquid mixed meal

3. Skipping the insulin bolus Insulin will be administered subcutaneously, with the dose determined based on the composition of the liquid mixed meal.

To correct for attenuation, the investigators will perform one ultra-low dose, non-contrast enhanced CT scan on each study day.

Results will be presented as means ± SD when possible. Primary and secondary outcomes will be analyzed using a two-way mixed model of linear regression with repeated measurements together with standard statistical methodology to compare results between study days. P-values < 0.05 will be considered statistically significant. Statistical analyses will be carried out using R and visualization with GraphPad Prism.

The investigators base the sample size on our primary endpoint visceral meal fat uptake. Based on a previous (unpublished) study from our group with a test / re-test design using18F-FTHA PET together with a mixed meal, we can estimate a sample size based on the repeatability coefficient (RCP) of 45% in visceral adipose tissue. With a significance level of 0.05 and power of 80% and, the investigators will need 10 individuals to detect a 15% difference in meal fat uptake in adipose tissue. In the event of participant dropout, additional individuals will be recruited to ensure the intended sample size is maintained.

Conditions

Postprandial Lipid Metabolism; Type 1 Diabetes (T1D)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Meal insulin bolus 20 min before consumption of a liquid mixed meal

Group Type: EXPERIMENTAL

400 mL Fresubin Energy Drink and 100 mL heavy cream with the addition of the 18F-FTHA radiotracer

Intervention Type: DIETARY_SUPPLEMENT

400 mL Fresubin Energy Drink and 100 mL heavy cream with the addition of the 18F-FTHA radiotracer

Meal insulin bolus 20 min after consumption of a liquid mixed meal

Group Type: EXPERIMENTAL

400 mL Fresubin Energy Drink and 100 mL heavy cream with the addition of the 18F-FTHA radiotracer

Intervention Type: DIETARY_SUPPLEMENT

400 mL Fresubin Energy Drink and 100 mL heavy cream with the addition of the 18F-FTHA radiotracer

Skipping the insulin bolus

Group Type: EXPERIMENTAL

400 mL Fresubin Energy Drink and 100 mL heavy cream with the addition of the 18F-FTHA radiotracer

Intervention Type: DIETARY_SUPPLEMENT

400 mL Fresubin Energy Drink and 100 mL heavy cream with the addition of the 18F-FTHA radiotracer

Interventions

400 mL Fresubin Energy Drink and 100 mL heavy cream with the addition of the 18F-FTHA radiotracer

400 mL Fresubin Energy Drink and 100 mL heavy cream with the addition of the 18F-FTHA radiotracer

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

• Type 1 diabetes duration > 3 years or c-peptide negative
• Written and informed consent

Exclusion Criteria

• Medicine with an impact on blood glucose or blood pressure
• Affected screening blood sample as evaluated by the clinical responsible investigator.
• Alcohol or substance abuse
• BMI > 35 kg/m2 or < 18.5 kg/m2
• Participation in other clinical trials involving ionized radiation within the last 6 months
• Lactose intolerance
• Doesn't speak and understand Danish.
• Severe claustrophobia.
• Commitment to special diets

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Aarhus

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Esben Søndergaard, MD, PhD

Role: STUDY_DIRECTOR

Steno Diabetes Center Aarhus, Aarhus University Hospital, 8200 Aarhus, Denmark

Locations

Department of Nuclear Medicine & PET-Centre, AUH Palle Juul-Jensens Blvd. 165, 8200 Aarhus N, Denmark and Medical Research Laboratories/Steno Diabetes Center Aarhus, AUH Palle Juul-Jensens Blvd. 11, 8200 Aarhus N, Denmark

Aarhus, , Denmark

Countries

Denmark

Central Contacts

Jens H. Voigt, MD

Role: CONTACT

Jens.voigt@clin.au.dk

0026395294

Esben Søndergaaard, MD, PhD

Role: CONTACT

Esben.sondergaard@clin.au.dk

004528730943

Facility Contacts

Jens H Voigt, MD

Role: primary

Jens.voigt@clin.au.dk

26395294

Other Identifiers

TiMed-T1D

Identifier Type: -

Identifier Source: org_study_id