Influence of Central Nervous Insulin Sensitivity on Insulin Secretion

NCT02870361 | Completed

• 1 other identifier: 086/2016BO1
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Insulin resistance is a central pathophysiological component of type 2 diabetes and is associated with a high risk of cardiovascular disease. The tissue in which it manifests are mainly muscle, liver, and adipose tissue. Since the transport of glucose to the brain is independent of insulin, this organ has traditionally not been studied in this regard. In animal experiments, however, knockout of the insulin receptor in the brain leads to obesity and peripheral insulin resistance. This finding of insulin action in the brain could also be confirmed in human studies. The investigators intend to investigate whether central nervous insulin action affects insulin secretion in humans. For this purpose, nasal insulin and placebo are administered 15 minutes before a hyperglycemic hyperinsulinemic clamps, which stimulate insulin secretion. Insulin sensitivity of the brain is measured by a an established protocol with functional magnetic resonance imaging before and after nasal insulin administration.

Conditions

Insulin Secretion

Outcome Measures

Primary Outcomes (1)

• Insulin secretion assessed as serum C-peptide levels during a hyperglycemic clamp

  0-10 min during hyperglycemic clamp and 10-90 min during hyperglycemic clamp

Secondary Outcomes (4)

• Correlation with brain insulin sensitivity

  15-30 minutes post insulin nasal spray

• Differential effects in lean and overweight

  0-10 min during hyperglycemic clamp and 10-90 min during hyperglycemic clamp

• Correlation with autonomous nervous system activity

  10 - 150 minutes post nasal spray

• Peripheral insulin sensitivity

  10-90 min and 70-90 min during hyperglycemic clamp

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

Interventions

intranasal insulin DRUG

Insulin nasal spray

Placebo DRUG

Placebo nasal spray

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• HbA1c ≤6.0%
• normal glucose tolerance during 75g oral glucose tolerance test (OGTT)

You may not qualify if:

• Not removable metal parts in or on the body
• manifest cardiovascular disease
• claustrophobia
• recent surgery (less than 3 months)
• Simultaneous participation in other studies
• Acute disease or infection within the last 4 weeks
• neurological and psychiatric disorders
• treatment with centrally acting drugs
• hemoglobin Hb \<13g / dl
• Hypersensitivity to any of the substances used

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, Willmann C, Jaghutriz BA, Vosseler A, Kubler C, Hund V, Scheffler K, Peter A, Haring HU, Preissl H, Kullmann S, Fritsche A. Insulin Action in the Hypothalamus Increases Second-Phase Insulin Secretion in Humans. Neuroendocrinology. 2020;110(11-12):929-937. doi: 10.1159/000504551. Epub 2019 Nov 5.

  PMID: 31689708 DERIVED

Study Officials

• Martin Heni, MD

  University Hospital Tuebingen

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: August 9, 2016
• First Posted: August 17, 2016
• Study Start: August 1, 2016
• Primary Completion: February 1, 2018
• Study Completion: April 1, 2018
• Last Updated: May 8, 2018

Record last verified: 2018-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)