The Effect of Central Insulin on Insulin Sensitivity and Energy Metabolism (Centrin)

June 2, 2023 updated by: German Diabetes Center

Insulin has a direct effect on the energy metabolism of the brain under basal conditions and has an effect on the hepatic glucose production, lipid metabolism and the secretion of various hormone. The effect of intranasal insulin on peripheral metabolism in humans supposedly is mediated by the vagus nerve.

The purpose of this study is to determine whether central insulin influences the human peripheral insulin sensitivity of liver and muscle and whether vagus nerve stimulation can mimick this effect.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Insulin has a direct effect on the energy metabolism of the brain under basal conditions and has an effect on the hepatic glucose production, lipid metabolism in the mouse model.

The purpose of this study is to determine whether central insulin influences the human peripheral insulin sensitivity of liver and muscle and energy metabolism. Intranasal insulin can be used in humans to deliver insulin to the brain and studies have shown that intranasal insulin might reduce food intake, lower body weight and modulate muscle glucose and adipose tissue lipid metabolism in himans. These effects are likely mediated by the vagus nerve as skeletal muscle insulin sensitization after intranasal insulin relates to parasympathetic tone activity (Heni et al. Diabetes 2014). Transcutaneous auricular vagus nerve stimulation (taVNS) activates non-invasively the sensory branches of the vagus nerve and is applied in humans as adjuvant treatment in drug-resistant epilepsy (Frangos et al. 2015). Thereby it can be used to examine whether the vagus nerve indeed mediates brain insulin signals to the periphery.

Here we aim to investigate the effects of intranasal insulin on hepatic glucose, lipid and energy metabolism. We further aim to test whether taVNS can mimick intranasal insulin effects on peripheral metabolism in humans.

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
    • Nordrhein- Westfalen
      • Düsseldorf, Nordrhein- Westfalen, Germany, 40225
        • German Diabetic Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

30 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Age ≥ 30 and ≤ 70 years
  • balanced gender ratio (50: 50)
  • BMI 20-25 kg/m² (normal weight subjects)
  • BMI 25-35 kg/m² (obese subjects)

Exclusion Criteria:

  • acute illness within the last 2 weeks before the examination
  • autoimmune diseases and disorders immune- compromised (leukocytes <5000/μl)
  • renal insufficiency (creatinine> 1.5 mg / dl)
  • heart disease, condition after heart attack
  • anemia (Hb <12 g / l, controls at each examination), blood donation within 4 weeks before the examination
  • participation in another study within 2 months before the examination
  • wear a metal or magnetic objects on or in the body
  • claustrophobia
  • use of immunomodulatory drugs (cortisol, antihistamines, aspirin)
  • thyroid disease
  • taking glitazones and insulin therapy
  • pregnancy, lactation, menstruation
  • cigarette smoking, use of alcohol or drugs, psychiatric disorders
  • risk for / or manifest AIDS (HIV) or hepatitis B or C
  • liver disease is not attributed to the existence of a non-alcoholic steatosis
  • night shift work or circumstances, which do not allow the normal day-night rhythm
  • bleeding disorders or disorders in wound healing
  • hypersensitivity to local anesthetics
  • malignant cancer
  • heart rhythm disorders
  • polyneuropathy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: intranasal insulin in patients
intranasal insulin is applied to diabetic patients under fasting conditions
Drug: intransal insulin
4x 40mU intranasal insulin
Other Names:
  • intranasal insulin
Experimental: intransal insulin in study participants
intranasal insulin is applied to healthy patients under fasting conditions
Drug: intransal insulin
4x 40mU intranasal insulin
Other Names:
  • intranasal insulin
Placebo Comparator: placebo in patients
placebo spray is applied intranasally in type 2 diabetes patients under fasting conditions
Drug: Placebo
Other Names:
  • intranasal placebo spray
Experimental: placebo in study participants
placebo spray is applied intranasally in healthy participants under fasting conditions
Drug: Placebo
Other Names:
  • intranasal placebo spray
Experimental: taNVS
Transcutanoues auricular vagus nerve stimulation is applied for 14 min in the external ear in healthy participants
Device: taVNS
Other Names:
  • transcutaneous auricular vagus nerve stimulation
Placebo Comparator: Sham stimulation
Sham stimulation in the ear lobe is applied for 14 min in healthy participants
Device: sham stimulation
Other Names:
  • sham stimulation in the ear lobe

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Insulin sensitivity
Time Frame: 6 months
Assessment of insulin sensitivity with gold standard methods
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Energy metabolism
Time Frame: 6 months
Energy metabolism is assessed from gold standard methods
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

German Diabetes Center

Investigators

  • Principal Investigator: Julia Szendrödi, MD, PhD, German Diabetes Center
  • Study Director: Michael Roden, MD, Prof, Germyn Diabetic Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2011

Primary Completion (Actual)

January 1, 2014

Study Completion (Actual)

June 1, 2014

Study Registration Dates

First Submitted

November 22, 2011

First Submitted That Met QC Criteria

November 23, 2011

First Posted (Estimated)

November 24, 2011

Study Record Updates

Last Update Posted (Actual)

June 5, 2023

Last Update Submitted That Met QC Criteria

June 2, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Centrin

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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