The Effect of Central Insulin on Insulin Sensitivity and Energy Metabolism

NCT ID: NCT01479075

Last Updated: 2023-06-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-08-31
• Study Completion Date: 2014-06-30

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.

Conditions

Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

intranasal insulin in patients

intranasal insulin is applied to diabetic patients under fasting conditions

Group Type: EXPERIMENTAL

intransal insulin

Intervention Type: DRUG

4x 40mU intranasal insulin

intransal insulin in study participants

intranasal insulin is applied to healthy patients under fasting conditions

Group Type: EXPERIMENTAL

intransal insulin

Intervention Type: DRUG

4x 40mU intranasal insulin

placebo in patients

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

placebo in study participants

placebo spray is applied intranasally in healthy participants under fasting conditions

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

taNVS

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

Group Type: EXPERIMENTAL

taVNS

Intervention Type: DEVICE

Sham stimulation

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

Group Type: PLACEBO_COMPARATOR

sham stimulation

Intervention Type: DEVICE

Interventions

intransal insulin

4x 40mU intranasal insulin

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

taVNS

Intervention Type: DEVICE

sham stimulation

Intervention Type: DEVICE

Other Intervention Names

intranasal insulin; intranasal placebo spray; transcutaneous auricular vagus nerve stimulation; sham stimulation in the ear lobe

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

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

German Diabetes Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Roden, MD, Prof

Role: STUDY_DIRECTOR

Germyn Diabetic Center

Julia Szendrödi, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

German Diabetes Center

Locations

German Diabetic Center

Düsseldorf, North Rhine-Westphalia, Germany

Countries

Germany

References

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.

Reference Type: BACKGROUND

PMID: 25573069 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25028522 (View on PubMed)

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.

Reference Type: RESULT

PMID: 25576060 (View on PubMed)

Other Identifiers

Centrin

Identifier Type: -

Identifier Source: org_study_id