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

NCT02468999 | Completed

• 1 other identifier: 402/2014B01
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Insulin Resistance

Keywords

Intranasal insulin

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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

Secondary Outcomes (2)

• Autonomous nervous system activity

  baseline, 70-90 min, 170-210 min and 280-300 min

• Regional brain insulin sensitivity

  30 min

Study Arms (2)

insulin nasal spray

ACTIVE COMPARATOR

160 Units of human insulin as nasal spray

Drug: human insulin

placebo nasal spray

PLACEBO COMPARATOR

Nasal spray containing placebo solution

Drug: human insulin

Interventions

human insulin DRUG

insulin nasal spray; placebo nasal spray

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital Tuebingen: lead

Study Sites (1)

University of Tuebingen, Department of Internal Medicine IV

Tübingen, 72076, Germany

Location

Related Publications (1)

• Heni M, Wagner R, Kullmann S, Gancheva S, Roden M, Peter A, Stefan N, Preissl H, Haring HU, Fritsche A. Hypothalamic and Striatal Insulin Action Suppresses Endogenous Glucose Production and May Stimulate Glucose Uptake During Hyperinsulinemia in Lean but Not in Overweight Men. Diabetes. 2017 Jul;66(7):1797-1806. doi: 10.2337/db16-1380. Epub 2017 Feb 7.

  PMID: 28174292 DERIVED

MeSH Terms

Conditions

Insulin Resistance

Interventions

Insulin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Andreas Fritsche, Prof. Dr.

  University Hospital Tuebingen

  PRINCIPAL INVESTIGATOR

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: March 24, 2015
• First Posted: June 11, 2015
• Study Start: January 1, 2015
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: January 8, 2016

Record last verified: 2016-01

Locations

DE (1)