Effect of Weight Loss on Brain Insulin Sensitivity in Humans

Effekt Von Gewichtsabnahme Auf Die zentralnervöse Insulinresistenz Des Menschen

Obesity if known to be associated with brain insulin resistance in humans. This condition has not only implication for the brain but also for whole-body energy homeostasis. Research in rodents indicates that weight loss is able to improve insulin sensitivity of the brain. The current project will test this hypothesis in humans. Therefore, brain insulin sensitivity will be assessed by fMRI in combination with intranasal insulin administration, using an established protocol. Furthermore, effects of daily administration of insulin nasal spray (versus placebo) over 8 weeks will be assessed as secondary (exploratory) variables.

Study Overview

• Status: Recruiting
• Conditions: Insulin Resistance
• Intervention / Treatment: Other: nasal insulin; Other: placebo spray

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Andreas Fritsche, MD; Phone Number: +49 7071 29 80687; Email: andreas.fritsche@med.uni-tuebingen.de

Study Locations

• Germany
  • Tübingen, Germany, 72076
    • Recruiting
    • University of Tuebingen, Department of Internal Medicine IV
    • Contact: Andreas Fritsche, Prof. Dr.; Phone Number: +49 7071 29 82714; Email: andreas.fritsche@med.uni-tuebingen.de
    • Sub-Investigator: Martin Heni, MD
    • Contact: Stephanie Kullmann, Prof. Dr.; Phone Number: +49 7071 29 87703; Email: stephanie.kullmann@med.uni-tuebingen.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• HbA1c <6.5%
• Age between 40 and 75 years
• No intake of antidiabetic drugs or drugs for weight reduction
• no steroid intake
• Stable medication over 10 weeks before the start of the study

Exclusion Criteria:

• Persons who wear non-removable metal parts in or on the body.
• Persons with reduced temperature sensitivity and / or increased sensitivity to heating of the body
• Cardiovascular disease can not be ruled out, e.g. manifest coronary heart disease, heart failure greater than NYHA 2, previous heart attack, stroke condition
• Persons with hearing impairment or increased sensitivity to loud noises
• People with claustrophobia
• Minors or non-consenting subjects are also excluded
• Subjects with an operation less than 3 months
• Simultaneous participation in other studies
• Neurological and psychiatric disorders
• Subjects with hemoglobin Hb <11 g / dl
• Hypersensitivity to any of the substances used

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: nasal insulin; daily administration of 160 U of human insulin as nasal spray	Other: nasal insulin
Placebo Comparator: placebo spray; daily administration of placebo solution as nasal spray	Other: placebo spray

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
brain insulin sensitivity	fMRI measurement will be performed before and after administration of 160 U of human insulin as nasal spray. Changes in regional activity will be quantified to assess regional brain insulin sensitivity.	30 minutes after administration of nasal insulin

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of daily administration of 160 U nasal insulin or placebo over 8 weeks on body weight.	Participants will receive nasal insulin or placebo in a double-blind randomized fashion. Before and after 8 weeks body weight will be recorded.	8 weeks
Effect of daily administration of 160 U nasal insulin or placebo over 8 weeks on glucose tolerance .	Participants will receive nasal insulin or placebo in a double-blind randomized fashion. Before and after 8 weeks glucose tolerance will be assessed using a 75 g oral glucose tolerance test.	8 weeks
Effect of daily administration of 160 U nasal insulin or placebo over 8 weeks on body composition .	Participants will receive nasal insulin or placebo in a double-blind randomized fashion. Before and after 8 weeks body composition will be addressed by whole-body MRI and liver MRS.	8 weeks
whole-body insulin sensitivity	Insulin sensitivity will be estimated from a frequent-sampling 75 g oral glucose tolerance test using the Matsuda formula.	2 hours
Glucose tolerance	a 75 g oral glucose tolerance test will be performed. Glucose tolerance will be defined by the American Diabetes Association criteria.	2 hours
Cognitive function	cognitive function will be addressed by neuropsychological testing.	1 hours

Collaborators and Investigators

• Sponsor: University Hospital Tuebingen
• Investigators: Principal Investigator: Andreas Fritsche, MD, University of Tübingen Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2016
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: December 1, 2016
• First Submitted That Met QC Criteria: December 12, 2016
• First Posted (Estimated): December 13, 2016

Study Record Updates

• Last Update Posted (Actual): February 2, 2024
• Last Update Submitted That Met QC Criteria: February 1, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Insulin Resistance; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin
• Other Study ID Numbers: 8 weeks study

Plan for Individual participant data (IPD)

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