"Effect of Central Insulin Administration on Whole-body Insulin Sensitivity in Women"

The human brain is an insulin sensitive organ. Brain insulin action modulates peripheral insulin sensitivity in young lean men. As a underlying mechanism, the investigators previously detected suppression of endogenous glucose production and stimulation of glucose disappearance to peripheral tissue in response to brain insulin delivery by nasal spray. Whether this holds true in young woman is unknown, since differences in brain insulin response between sexes have been reported. The investigators will address this question by combining the delivery of insulin to the brain as nasal spray with hyperinsulinemic euglycemic clamp experiments in natural cycling women.

In the planned randomized, placebo controlled cross-over study, female participants will undergo four hyperinsulinemic euglycemic experiments with tracer dilution, two in the first phase and two in the second phase of their menstrual cycle. On one of the study days per menstrual phase, subjects will receive intranasal insulin administration, on the other placebo spray. The protocol has been successfully applied previously in men. Based on the results of this trial, the investigators calculated a required sample size of N=10 for the planned study in women.

These experiments will help to better understand the role of brain insulin action in a broader sense. The results can be the basis for larger clinical trials that address the sex-specific impact of brain insulin resistance for glucose metabolism and diabetes risk.

Study Overview

• Status: Completed
• Conditions: Insulin Sensitivity
• Intervention / Treatment: Drug: intranasal insulin; Drug: Placebo spray

Detailed Description

"Effect of central insulin administration on whole-body insulin sensitivity in women" The human brain is an insulin sensitive organ. Brain insulin action modulates peripheral insulin sensitivity in young lean men. As a underlying mechanism, the investigators previously detected suppression of endogenous glucose production and stimulation of glucose disappearance to peripheral tissue in response to brain insulin delivery by nasal spray. Whether this holds true in young woman is unknown, since differences in brain insulin response between sexes have been reported. The investigators will address this question by combining the delivery of insulin to the brain as nasal spray with hyperinsulinemic euglycemic clamp experiments in natural cycling women.

In the planned randomized, placebo controlled cross-over study, female participants will undergo four hyperinsulinemic euglycemic experiments with tracer dilution, two in the first phase and two in the second phase of their menstrual cycle. On one of the study days per menstrual phase, subjects will receive intranasal insulin administration, on the other placebo spray. The protocol has been successfully applied previously in men. Based on the results of this trial, the investigators calculated a required sample size of N=10 for the planned study in women.

These experiments will help to better understand the role of brain insulin action in a broader sense. The results can be the basis for larger clinical trials that address the sex-specific impact of brain insulin resistance for glucose metabolism and diabetes risk.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Tuebingen, Germany, 72076
    • University of Tuebingen, Department of Internal Medicine IV

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 30 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• female volunteer adults
• HbA1c <6.0%
• Age between 18 and 30 years
• Standard routine laboratory
• No underlying diseases
• No medication
• No hormonal contraception
• Understanding of the explanations of the study and the instructions

Exclusion Criteria:

• Persons with limited temperature perception and / or increased temperature Sensitivity to warming of the body
• Cardiovascular disease, such as manifest coronary Heart disease, heart failure greater than NYHA 2, recent myocardial infarction
• People with a hearing disorder or increased sensitivity to loud Sounds
• persons with claustrophobia
• Minors or non-consenting subjects are also excluded
• Pregnancy or breastfeeding women
• Surgery less than 3 months ago
• Simultaneous participation in other interventional studies
• Acute illness or infection within the last 4 weeks
• Neurological and psychiatric disorders
• Subjects with hemoglobin Hb <12g / dl (at screening)
• Allergic diseases
• Individuals with a history of heparin-induced thrombocytopenia (HIT)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Insulin nasal spray; 160 Units of human insulin as nasal spray	Drug: intranasal insulin; application of 160 units human insulin
Placebo Comparator: Placebo nasal spray; Nasal spray containing placebo solution	Drug: Placebo spray; nasal spray containing placebo solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the peripheral insulin sensitivity	Effect of nasal insulin versus placebo on peripheral insulin sensitivity assessed by euglycemic hyperinsulinemic clamp.	60-90 minutes and 150-210 minutes during euglycemic clamp

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation with autonomous nervous system activity	Correlation of the change in peripheral insulin sensitivity by central insulin action with the simultaneous change of the autonomous nervous system (measured by heart rate variability).	70-80 minutes and 190-200 minutes during euglycemic clamp
Differential effects dependent on female sexual hormones	Correlation of the change in peripheral insulin sensitivity by central insulin action dependent on the time point in menstrual cycle	60-90 minutes and 150-210 minutes during euglycemic clamp
Effect of menstrual cycle on insulin sensitivity before spray application	Will be measured by hyperinsulinemic euglycemic clamp	60-90minutes
Effect of menstrual cycle on brain insulin sensitivity	Brain insulin sensitivity will be assessed by functional magnetic resonance imaging combined with intranasal insulin administration during the follicular and the luteal phase of the menstrual cycle	60-90 minutes
Effect of menstrual cycle on processing of food cues in the brain	Processing of food cues in the brain will be assessed by functional magnetic resonance imaging during the follicular and the luteal phase of the menstrual cycle	20 minutes

Collaborators and Investigators

• Sponsor: University Hospital Tuebingen

Study record dates

Study Major Dates

• Study Start (Actual): April 21, 2019
• Primary Completion (Actual): March 25, 2021
• Study Completion (Actual): April 30, 2021

Study Registration Dates

• First Submitted: April 15, 2019
• First Submitted That Met QC Criteria: April 25, 2019
• First Posted (Actual): April 26, 2019

Study Record Updates

• Last Update Posted (Actual): September 5, 2021
• Last Update Submitted That Met QC Criteria: September 2, 2021
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Hyperinsulinism; Hypersensitivity; Insulin Resistance; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin
• Other Study ID Numbers: 568/2018BO1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No