The Effect of Central Insulin on Insulin Sensitivity and Energy Metabolism

NCT01479075 | Completed Phase 4

• 1 other identifier: Centrin
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetes

Keywords

central insulin; insulin resistance; energy metabolism

Outcome Measures

Primary Outcomes (1)

• Insulin sensitivity

  Assessment of insulin sensitivity with gold standard methods

  6 months

Secondary Outcomes (1)

• Energy metabolism

  6 months

Study Arms (6)

intranasal insulin in patients

EXPERIMENTAL

intranasal insulin is applied to diabetic patients under fasting conditions

Drug: intransal insulin

intransal insulin in study participants

EXPERIMENTAL

intranasal insulin is applied to healthy patients under fasting conditions

Drug: intransal insulin

placebo in patients

PLACEBO COMPARATOR

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

Drug: Placebo

placebo in study participants

EXPERIMENTAL

placebo spray is applied intranasally in healthy participants under fasting conditions

Drug: Placebo

taNVS

EXPERIMENTAL

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

Device: taVNS

Sham stimulation

PLACEBO COMPARATOR

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

Device: sham stimulation

Interventions

intransal insulin DRUG

4x 40mU intranasal insulin

Also known as: intranasal insulin

intranasal insulin in patients; intransal insulin in study participants

Placebo DRUG

Also known as: intranasal placebo spray

placebo in patients; placebo in study participants

taVNS DEVICE

Also known as: transcutaneous auricular vagus nerve stimulation

taNVS

sham stimulation DEVICE

Also known as: sham stimulation in the ear lobe

Sham stimulation

Eligibility Criteria

• Age: 30 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• German Diabetes Center: lead

Study Sites (1)

German Diabetic Center

Düsseldorf, North Rhine-Westphalia, 40225, Germany

Location

Related Publications (3)

• 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.

  PMID: 25573069 BACKGROUND

• 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.

  PMID: 25028522 BACKGROUND

• 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.

  PMID: 25576060 RESULT

MeSH Terms

Conditions

Diabetes Mellitus; Insulin Resistance

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism

Study Officials

• Michael Roden, MD, Prof

  Germyn Diabetic Center

  STUDY DIRECTOR

• Julia Szendrödi, MD, PhD

  German Diabetes Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2011
• First Posted: November 24, 2011
• Study Start: August 1, 2011
• Primary Completion: January 1, 2014
• Study Completion: June 1, 2014
• Last Updated: June 5, 2023

Record last verified: 2023-06

Locations

DE (1)