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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01479075
Recruitment Status : Active, not recruiting
First Posted : November 24, 2011
Last Update Posted : May 31, 2017
Sponsor:
Information provided by (Responsible Party):

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.


Condition or disease Intervention/treatment Phase
Diabetes Drug: intransal insulin Drug: Placebo Device: taVNS Device: sham stimulation Phase 4

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 Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: The Effect of Central Insulin on Insulin Sensitivity and Energy Metabolism
Study Start Date : August 2011
Estimated Primary Completion Date : January 2018
Estimated Study Completion Date : June 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Allergy
U.S. FDA Resources

Arms and Interventions

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 Name: 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 Name: intranasal insulin
Placebo Comparator: placebo in patients
placebo spray is applied intranasally in type 2 diabetes patients under fasting conditions
Drug: Placebo
Other Name: intranasal placebo spray
Experimental: placebo in study participants
placebo spray is applied intranasally in healthy participants under fasting conditions
Drug: Placebo
Other Name: 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 Name: 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 Name: sham stimulation in the ear lobe


Outcome Measures

Primary Outcome Measures :
  1. Insulin sensitivity [ Time Frame: 6 months ]
    Assessment of insulin sensitivity with gold standard methods


Secondary Outcome Measures :
  1. Energy metabolism [ Time Frame: 6 months ]
    Energy metabolism is assessed from gold standard methods


Eligibility Criteria

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Ages Eligible for Study:   30 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01479075


Locations
Germany
German Diabetic Center
Düsseldorf, Nordrhein- Westfalen, Germany, 40225
Sponsors and Collaborators
German Diabetes Center
Investigators
Study Director: Michael Roden, MD, Prof Germyn Diabetic Center
Principal Investigator: Julia Szendrödi, MD, PhD German Diabetes Center
More Information