Relative Contribution of Brain Insulin Action for Postprandial Metabolism (BrainInsPPM)

University of Ulm

Status: Active, not recruiting

Conditions: Glucose Metabolism Disorders

Treatments: Other: Oral glucose tolerance test with double-tracer dilution and intranasal insulin spray; Other: Oral glucose tolerance test with double-tracer dilution and intranasal placebo spray

Study type: Interventional

Funder types: Other

Identifiers

NCT06295640

300/2022

Details and patient eligibility

About

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.

Full 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.

Enrollment: 31 patients

Sex: All

Ages: 18 to 30 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Single Blind

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31 participants in 2 patient groups, including a placebo group

Intranasal insulin spray

Experimental group

Description:

160 Units of human insulin as nasal spray

Treatment:

Other: Oral glucose tolerance test with double-tracer dilution and intranasal insulin spray

Placebo spray

Placebo Comparator group

Description:

Nasal spray containing placebo solution

Treatment:

Other: Oral glucose tolerance test with double-tracer dilution and intranasal placebo spray