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

NCT03929419 | Completed

• 1 other identifier: 568/2018BO1
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Insulin Sensitivity

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Correlation with autonomous nervous system activity

  70-80 minutes and 190-200 minutes during euglycemic clamp

• Differential effects dependent on female sexual hormones

  60-90 minutes and 150-210 minutes during euglycemic clamp

• Effect of menstrual cycle on insulin sensitivity before spray application

  60-90minutes

• Effect of menstrual cycle on brain insulin sensitivity

  60-90 minutes

• Effect of menstrual cycle on processing of food cues in the brain

  20 minutes

Study Arms (2)

Insulin nasal spray

ACTIVE COMPARATOR

160 Units of human insulin as nasal spray

Drug: intranasal insulin

Placebo nasal spray

PLACEBO COMPARATOR

Nasal spray containing placebo solution

Drug: Placebo spray

Interventions

intranasal insulin DRUG

application of 160 units human insulin

Insulin nasal spray

Placebo spray DRUG

nasal spray containing placebo solution

Placebo nasal spray

Eligibility Criteria

• Age: 18 Years - 30 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• University Hospital Tuebingen: lead

Study Sites (1)

University of Tuebingen, Department of Internal Medicine IV

Tübingen, 72076, Germany

Location

Related Publications (1)

• Hummel J, Benkendorff C, Fritsche L, Prystupa K, Vosseler A, Gancheva S, Trenkamp S, Birkenfeld AL, Preissl H, Roden M, Haring HU, Fritsche A, Peter A, Wagner R, Kullmann S, Heni M. Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase. Nat Metab. 2023 Sep;5(9):1475-1482. doi: 10.1038/s42255-023-00869-w. Epub 2023 Sep 21.

  PMID: 37735274 DERIVED

MeSH Terms

Conditions

Insulin Resistance

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2019
• First Posted: April 26, 2019
• Study Start: April 21, 2019
• Primary Completion: March 25, 2021
• Study Completion: April 30, 2021
• Last Updated: September 5, 2021

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)