Influence of Central Nervous Insulin Action on Insulin Sensitivity of Peripheral Organs in Lean Versus Overweight Humans

Insulin Resistance Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02468999
• Other study ID #: 402/2014B01
• Status: Completed
• Phase: N/A
• First received: March 24, 2015
• Last updated: January 7, 2016
• Start date: January 2015
• Est. completion date: December 2015

Study information

• Verified date: January 2016
• Source: University Hospital Tuebingen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Ethics Commission
• Study type: Interventional

Clinical Trial Summary

Research in animals and first experiments in humans indicate that insulin action in the brain regulates peripheral insulin sensitivity. One major organ might be the liver. Previous studies in humans showed that the human brain is an insulin sensitive organ in lean but not in overweight/obese persons. Therefore, this study will include lean versus overweight/obese persons.

In this study, insulin action will be introduced by intranasal insulin administration in lean and overweight humans. As a control, placebo spray will be administered. To mimick the known spill over of small amounts of intranasal insulin into circulation, a small bolus of insulin will be administered over 15 minutes following placebo spray application.

Peripheral insulin sensitivity will be assessed by hyperinsulinemic-euglycemic glucose clamp and glucose uptake and endogenous glucose production will be assessed by tracer dilution technique. Autonomous nervous system activity will be addressed by heart rate variability. Involved brain areas will be addressed by fMRI before and after nasal insulin application.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

• Male volunteers (lean or overweight/obese)

• HbA1c <6.0%

• Age between 18 and 40 years

• healthy as assessed by physician

• Understanding the explanations about the study and instructions

Exclusion Criteria:

• non-removable metal parts in or on the body

• Persons with reduced temperature sensation and / or increased sensitivity to warming of the body

• Cardiovascular disease can not be excluded, such as evident coronary heart disease, congestive heart failure NYHA greater than 2, history of coronary artery disease

• History of stroke

• Persons with a hearing disorder or increased sensitivity to loud noises

• People with claustrophobia

• Subjects in which less than 3 months have passed since surgery

• Simultaneous participation in other studies

• Acute disease or infection within the last 4 weeks

• Neurological and psychiatric disorders

• Subjects with hemoglobin Hb <13g / dl

• Heparin-induced thrombocytopenia people with a (HIT) in prehistory

• Allergies to any of the used solutions/devices

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Single Blind (Subject), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Insulin Resistance

Intervention

Drug:
• human insulin

Locations

Country	Name	City	State
Germany	University of Tuebingen, Department of Internal Medicine IV	Tübingen

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Tuebingen

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in glucose infusion rate during hyperinsulinemic euglycemic glucose clamp from before to after nasal spray application in lean persons		Change from 70-90 min (before spray) to 170-210 min and to 280-300 min	No
Primary	Change in endogenous glucose production from before to after nasal spray application in lean persons	Will be assessed by tracer dilution technique.	Change from 70-90 min (before spray) to 170-210 min and to 280-300 min	No
Primary	Differences in insulin response between lean and overweight persons	Will be assessed as plasma insulin and C-peptide concentrations.	up to 210 minutes post nasal spray administration	No
Secondary	Autonomous nervous system activity	Will be assessed by analysis of heart rate variability.	baseline, 70-90 min, 170-210 min and 280-300 min	No
Secondary	Regional brain insulin sensitivity	Will be assessed on an additional study day by fMRI before and after intranasal insulin administration	30 min	No