Clinical trial NCT06295640: Relative Contribution of Brain Insulin Action for Postprandial Metabolism
Official title: Relative Contribution of Brain Insulin Action for Postprandial Metabolism
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Glucose Metabolism Disorders
Keywords: postprandial glucose metabolism
brain insulin action
insulin sensitivity
insulin secretion
endogenous glucose production
menstrual cycle
sex differences
proglucagon cleavage products
Lead sponsor: University of Ulm
Sponsor class: OTHER
First posted: 2024-03-06
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 30
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Randomized, controlled, cross-over design for men. Randomized, controlled, 2x2 factorial cross-over design for women taking the menstrual cycle phase into account.
Primary purpose: BASIC_SCIENCE

Brief summary: The goal of this clinical trial is to clarify (i) the contribution of brain insulin action on regulation of systemic metabolism, (ii) sex-specific differences in the central regulation and (iii) the influence of the menstrual cycle in women.

Therefore, participants will undergo oral glucose tolerance tests combined with a double tracer dilution technique. This approach will be compared between days with insulin delivery to the brain as nasal spray and days with placebo spray.

Detailed description: This research project aims to investigate to what extent brain insulin action is responsible for the control of postprandial metabolism compared to direct effects of insulin in peripheral target tissues. Furthermore, the study will investigate sex differences and the influence of the menstrual cycle on brain-derived coordination of postprandial signaling for metabolic control.

Therefore, insulin action in the brain will be introduced by application of insulin as nasal spray (on one day) versus carrier solution as placebo nasal spray (on another day) in a randomized, blinded fashion. Spray administration will be performed 15 minutes before a 75 gram oral glucose tolerance test that will introduce a postprandial state. On placebo day, the known spillover of tiny amounts of nasal insulin into the systemic circulation will be mimicked by an appropriate i.v. insulin bolus. This approach will be combined with a double-tracer dilution technique. Labeled glucose (\[6,6-2H\]glucose) will be infused 120 minutes before and during the OGTT (180 min) and will be used to address endogenous glucose production. The glucose drink from the OGTT will be enriched with \[U-13C6\]glucose to compute the glucose appearance rate (Ra). Basal endogenous glucose production will be calculated as well as post-load endogenous glucose production and rates of glucose disappearances (Rd). Using this approach, brain-derived regulation of postprandial metabolism including endogenous glucose production, glucose disappearance, insulin secretion, and secretion of proglucagon-cleavage products (incretins) will be examined.

Eligibility criteria: Inclusion Criteria:

* BMI \< 24 kg/m2
* no known primary diseases
* no hormonal contraception

Exclusion Criteria:

* Alcohol or drug abuse
* Smoking
* At screening: Hb \< 12 g/dl for women and Hb \< 14 g/dl for men
* Any (clinical) condition that would endanger participant's safety or question scientific success according to a physician's opinion.

Primary outcomes:
measure: Endogenous glucose production
timeFrame: -120 minutes - 180 minutes during oral glucose tolerance test
measure: Rate of glucose disappearance
timeFrame: -120 minutes - 180 minutes during oral glucose tolerance test
Secondary outcomes:
measure: Proglucagon cleavage products
timeFrame: 0-120 minutes during oral glucose tolerance test
measure: Glucose tolerance
timeFrame: 0-120 minutes during oral glucose tolerance test
measure: Whole-body insulin sensitivity
timeFrame: 0-120 minutes during oral glucose tolerance test
measure: Insulin secretion
timeFrame: 0-180 minutes during oral glucose tolerance test
measure: Post-absorptive energy expenditure
timeFrame: 30 minutes and 180 minutes during oral glucose tolerance test
measure: Sex differences
timeFrame: -120 minutes - 180 minutes during oral glucose tolerance test
measure: Menstrual cycle effects
timeFrame: -120 minutes - 180 minutes during oral glucose tolerance test
measure: Autonomic nervous system activity
timeFrame: -15 minutes - 180 minutes during oral glucose tolerance test
Other outcomes:
Locations:
city: Ulm
country: Germany
facility: Universityhospital Ulm
Study officials:
affiliation: University of Ulm
name: Martin Heni, MD
role: PRINCIPAL_INVESTIGATOR
References: