Overview

This trial is active, not recruiting.

Condition healthy subjects
Treatments intranasal insulin administration, insulin dilution buffer (novo nordisk), 1h magnetic resonance spectroscopy
Phase phase 2
Sponsor Medical University of Vienna
Start date September 2014
End date July 2016
Trial size 20 participants
Trial identifier NCT02164032, 2013-004463-32, INTO_humans

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose basic science
Arm
(Placebo Comparator)
During a subsequent 4-week treatment phase subjects will be randomly assigned to receive 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. Ectopic lipid content and heart function will be assessed weekly by non-invasive 1H magnetic resonance spectroscopy.
insulin dilution buffer (novo nordisk) vehicle
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
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.
(Active Comparator)
During a subsequent 4-week treatment phase subjects will be randomly assigned to receive 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. Ectopic lipid content and heart function will be assessed weekly by non-invasive 1H magnetic resonance spectroscopy.
intranasal insulin administration insulin Actrapid
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
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.

Primary Outcomes

Measure
Changes in total lipid content in the liver
time frame: one week before & at baseline & 1,2,3 and 4 weeks after intranasal insulin administration

Secondary Outcomes

Measure
Changes of hepatic Lipid composition
time frame: one week before & baseline & 1,2,3 and 4 weeks after intranasal insulin administration
Changes of myocardial lipid content
time frame: baseline, 2 and 4 weeks after intranasal insulin administration
Changes of myocardial lipid composition
time frame: baseline, 2 and 4 weeks after intranasal insulin administration
Changes of skeletal muscle lipid content
time frame: baseline, 2 and 4 weeks after intranasal insulin administration
Changes of lipid composition in skeletal muscle
time frame: baseline, 2 and 4 weeks after intranasal insulin administration
changes in heart function
time frame: baseline, 2 and 4 weeks after intranasal insulin administration

Eligibility Criteria

Male participants from 18 years up to 65 years old.

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].

Additional Information

Official title The Role of IntraNasal Insulin in Regulating HepaTic Lipid COntent in HUMANS a Randomized, Controlled, Double Blinded Trial
Principal investigator Michael Krebs, MD, Prof.
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by Medical University of Vienna.