The Role of IntraNasal Insulin in Regulating HepaTic Lipid COntent in HUMANS

Healthy Subjects Clinical Trial

— INTO_humans  

Official title:

The Role of IntraNasal Insulin in Regulating HepaTic Lipid COntent in HUMANS a Randomized, Controlled, Double Blinded Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02164032
• Other study ID #: INTO_humans
• Secondary ID: 2013-004463-32
• Status: Active, not recruiting
• Phase: Phase 2
• First received: June 12, 2014
• Last updated: September 26, 2016
• Start date: September 2014
• Est. completion date: December 2016

Study information

• Verified date: September 2016
• Source: Medical University of Vienna
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Non-alcoholic fatty liver disease (NAFLD) is a common human liver pathology, closely associated with the obesity pandemic and insulin resistance. In the insulin resistant state the liver remains sensitive to pro-lipogenic signals of insulin, which further promote lipid accumulation. Secretion of very-low-density-lipoproteins (VLDL), the main carriers of triglycerides (TG) in the plasma, is the principal pathway for the liver to mobilize and dispose of lipids. Thus, hepatic TG export must not be too low in order to prevent steatosis. Our preliminary data from animal experiments suggest that enhanced brain insulin signaling promotes hepatic VLDL secretion, and reduces lipid accumulation in the liver. It remains to be tested whether other insulin sensitive tissues, such as the myocardium or the skeletal muscle, are also affected. In humans, neuropeptides, including insulin, can be delivered to the brain via an intranasal (IN) route of administration, without causing relevant systemic side effects.

Therefore, we hypothesize that by enhancing brain insulin signaling using chronic IN insulin administration hepatic TG export increases and prohibits lipid accumulation in the liver and other insulin sensitive tissues, such as the myocardium and the skeletal muscle.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 20
• Est. completion date: December 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• BMI 22 - 27 kg/m2

• Age between 18 - 65 years

• Male sex

Exclusion Criteria:

• smoking

• regular medication

• metabolic or liver illnesses

• tendency towards claustrophobia

• Chronic sinusitis, diagnosed nasal polyposis, diagnosed severe septum deviation

• metal devices or other magnetic material in or on the subjects body which will be hazardous for NMR investigation [heart pacemaker, brain (aneurysm) clip, nerve stimulators, electrodes, ear implants, post coronary by-pass graft (epicardial pace wires), penile implants, colored contact lenses, patch to deliver medications through the skin, coiled spring intrauterine device, vascular filter for blood clots, orthodontic braces, shunt-spinal or ventricular, any metal implants (rods, joints, plates, pins, screws, nails, or clips), embolization coil, or any metal fragments or shrapnel in the body].

Related Conditions & MeSH terms

• Healthy Subjects

Intervention

Drug:
• Intranasal insulin administration
intranasal insulin (40 IE) Actrapid (100IE/mL); two 0.1 ml puffs per nostril) or placebo (insulin dilution buffer Novo Nordisk; two 0.1 ml puffs per nostril) four times a day (in total 160 IE Actrapid per day) before each main meal and before going to bed. 40 IE IN insulin enhances insulin concentration in the CSF without any changes in systemic insulin and glucose concentration, and no risk for hypoglycemia
• Insulin Dilution Buffer (Novo Nordisk)
intranasal insulin (40 IE) Actrapid (100IE/mL); two 0.1 ml puffs per nostril) or placebo (insulin dilution buffer Novo Nordisk; two 0.1 ml puffs per nostril) four times a day (in total 160 IE Actrapid per day) before each main meal and before going to bed. 40 IE IN insulin enhances insulin concentration in the CSF without any changes in systemic insulin and glucose concentration, and no risk for hypoglycemia

Other:
• 1H magnetic resonance spectroscopy
1H MR spectroscopy and imaging will be performed on the on on the 3.0-T Tim Trio System (Siemens Erlangen Germany). MR Spectroscopy and imaging measurements will last no more than 90 minutes all together.

Locations

Country	Name	City	State
Austria	Medical University Of Vienna, Department of Internal Medicine III	Vienna

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Vienna

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Changes of parameters of glucose and lipid metabolism	fasting Glucose, HbA1c, Cholesterol, LDL, HDL, TGs, non-HDL Cholesterol, FFAs	one week before & baseline & 1,2,3 and 4 weeks after initiation of intranasal insulin administration
Other	Lipid composition in plasma		one week before & at baseline & 1,2,3 and 4 weeks after intranasal insulin administration
Primary	Changes in total lipid content in the liver	1H magnetic resonance spectroscopy	one week before & at baseline & 1,2,3 and 4 weeks after intranasal insulin administration
Secondary	Changes of hepatic Lipid composition	1H magnetic resonance spectroscopy	one week before & baseline & 1,2,3 and 4 weeks after intranasal insulin administration
Secondary	Changes of myocardial lipid content	1H magnetic resonance spectroscopy	baseline, 2 and 4 weeks after intranasal insulin administration
Secondary	Changes of myocardial lipid composition	1H magnetic resonance spectroscopy	baseline, 2 and 4 weeks after intranasal insulin administration
Secondary	Changes of skeletal muscle lipid content	1H magnetic resonance spectroscopy	baseline, 2 and 4 weeks after intranasal insulin administration
Secondary	Changes of lipid composition in skeletal muscle	1H magnetic resonance spectroscopy	baseline, 2 and 4 weeks after intranasal insulin administration
Secondary	changes in heart function	magnetic resonance imaging	baseline, 2 and 4 weeks after intranasal insulin administration