Clinical trial NCT02164032: The Role of IntraNasal Insulin in Regulating HepaTic Lipid COntent in HUMANS
Official title: The Role of IntraNasal Insulin in Regulating HepaTic Lipid COntent in HUMANS a Randomized, Controlled, Double Blinded Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Healthy Subjects
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
First posted: 2014-06-16
Enrollment: 20
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief 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.


Eligibility criteria: 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 \[heart pacemaker, brain (aneurysm) clip, nerve stimulators, electrodes, ear implants, post coronary by-pass graft (epicardial pace wires), penile implants, colored contact lenses, patch to deliver medications through the skin, coiled spring intrauterine device, vascular filter for blood clots, orthodontic braces, shunt-spinal or ventricular, any metal implants (rods, joints, plates, pins, screws, nails, or clips), embolization coil, or any metal fragments or shrapnel in the body\].

Primary outcomes:
measure: Changes in total lipid content in the liver
timeFrame: one week before & at baseline & 1,2,3 and 4 weeks after intranasal insulin administration
Secondary outcomes:
measure: Changes of hepatic Lipid composition
timeFrame: one week before & baseline & 1,2,3 and 4 weeks after intranasal insulin administration
measure: Changes of myocardial lipid content
timeFrame: baseline, 2 and 4 weeks after intranasal insulin administration
measure: Changes of myocardial lipid composition
timeFrame: baseline, 2 and 4 weeks after intranasal insulin administration
measure: Changes of skeletal muscle lipid content
timeFrame: baseline, 2 and 4 weeks after intranasal insulin administration
measure: Changes of lipid composition in skeletal muscle
timeFrame: baseline, 2 and 4 weeks after intranasal insulin administration
measure: changes in heart function
timeFrame: baseline, 2 and 4 weeks after intranasal insulin administration
Other outcomes:
measure: Changes of parameters of glucose and lipid metabolism
timeFrame: one week before & baseline & 1,2,3 and 4 weeks after initiation of intranasal insulin administration
measure: Lipid composition in plasma
timeFrame: one week before & at baseline & 1,2,3 and 4 weeks after intranasal insulin administration
Locations:
city: Vienna
country: Austria
facility: Medical University Of Vienna, Department of Internal Medicine III
Study officials:
affiliation: Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria
name: Michael Krebs, MD, Prof.
role: PRINCIPAL_INVESTIGATOR
References: