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

Primary Purpose

Diabetes

Status
Completed
Phase
Phase 4
Locations
Germany
Study Type
Interventional
Intervention
intransal insulin
Placebo
taVNS
sham stimulation
Sponsored by
German Diabetes Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetes focused on measuring central insulin, insulin resistance, energy metabolism

Eligibility Criteria

30 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • German Diabetic Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Placebo Comparator

Experimental

Experimental

Placebo Comparator

Arm Label

intranasal insulin in patients

intransal insulin in study participants

placebo in patients

placebo in study participants

taNVS

Sham stimulation

Arm Description

intranasal insulin is applied to diabetic patients under fasting conditions

intranasal insulin is applied to healthy patients under fasting conditions

placebo spray is applied intranasally in type 2 diabetes patients under fasting conditions

placebo spray is applied intranasally in healthy participants under fasting conditions

Transcutanoues auricular vagus nerve stimulation is applied for 14 min in the external ear in healthy participants

Sham stimulation in the ear lobe is applied for 14 min in healthy participants

Outcomes

Primary Outcome Measures

Insulin sensitivity
Assessment of insulin sensitivity with gold standard methods

Secondary Outcome Measures

Energy metabolism
Energy metabolism is assessed from gold standard methods

Full Information

First Posted
November 22, 2011
Last Updated
June 2, 2023
Sponsor
German Diabetes Center
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1. Study Identification

Unique Protocol Identification Number
NCT01479075
Brief Title
The Effect of Central Insulin on Insulin Sensitivity and Energy Metabolism
Acronym
Centrin
Official Title
The Effect of Central Insulin on Insulin Sensitivity and Energy Metabolism
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
August 2011 (Actual)
Primary Completion Date
January 2014 (Actual)
Study Completion Date
June 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
German Diabetes Center

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes
Keywords
central insulin, insulin resistance, energy metabolism

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
Participant
Allocation
Randomized
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
intranasal insulin in patients
Arm Type
Experimental
Arm Description
intranasal insulin is applied to diabetic patients under fasting conditions
Arm Title
intransal insulin in study participants
Arm Type
Experimental
Arm Description
intranasal insulin is applied to healthy patients under fasting conditions
Arm Title
placebo in patients
Arm Type
Placebo Comparator
Arm Description
placebo spray is applied intranasally in type 2 diabetes patients under fasting conditions
Arm Title
placebo in study participants
Arm Type
Experimental
Arm Description
placebo spray is applied intranasally in healthy participants under fasting conditions
Arm Title
taNVS
Arm Type
Experimental
Arm Description
Transcutanoues auricular vagus nerve stimulation is applied for 14 min in the external ear in healthy participants
Arm Title
Sham stimulation
Arm Type
Placebo Comparator
Arm Description
Sham stimulation in the ear lobe is applied for 14 min in healthy participants
Intervention Type
Drug
Intervention Name(s)
intransal insulin
Other Intervention Name(s)
intranasal insulin
Intervention Description
4x 40mU intranasal insulin
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
intranasal placebo spray
Intervention Type
Device
Intervention Name(s)
taVNS
Other Intervention Name(s)
transcutaneous auricular vagus nerve stimulation
Intervention Type
Device
Intervention Name(s)
sham stimulation
Other Intervention Name(s)
sham stimulation in the ear lobe
Primary Outcome Measure Information:
Title
Insulin sensitivity
Description
Assessment of insulin sensitivity with gold standard methods
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Energy metabolism
Description
Energy metabolism is assessed from gold standard methods
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Roden, MD, Prof
Organizational Affiliation
Germyn Diabetic Center
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Julia Szendrödi, MD, PhD
Organizational Affiliation
German Diabetes Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
German Diabetic Center
City
Düsseldorf
State/Province
Nordrhein- Westfalen
ZIP/Postal Code
40225
Country
Germany

12. IPD Sharing Statement

Citations:
PubMed Identifier
25573069
Citation
Frangos E, Ellrich J, Komisaruk BR. Non-invasive Access to the Vagus Nerve Central Projections via Electrical Stimulation of the External Ear: fMRI Evidence in Humans. Brain Stimul. 2015 May-Jun;8(3):624-36. doi: 10.1016/j.brs.2014.11.018. Epub 2014 Dec 6.
Results Reference
background
PubMed Identifier
25028522
Citation
Heni M, Wagner R, Kullmann S, Veit R, Mat Husin H, Linder K, Benkendorff C, Peter A, Stefan N, Haring HU, Preissl H, Fritsche A. Central insulin administration improves whole-body insulin sensitivity via hypothalamus and parasympathetic outputs in men. Diabetes. 2014 Dec;63(12):4083-8. doi: 10.2337/db14-0477. Epub 2014 Jul 15.
Results Reference
background
PubMed Identifier
25576060
Citation
Gancheva S, Koliaki C, Bierwagen A, Nowotny P, Heni M, Fritsche A, Haring HU, Szendroedi J, Roden M. Effects of intranasal insulin on hepatic fat accumulation and energy metabolism in humans. Diabetes. 2015 Jun;64(6):1966-75. doi: 10.2337/db14-0892. Epub 2015 Jan 9.
Results Reference
result

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The Effect of Central Insulin on Insulin Sensitivity and Energy Metabolism

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