The Role of IntraNasal Insulin in Regulating HepaTic Lipid COntent in HUMANS (INTO_humans)
The Role of IntraNasal Insulin in Regulating HepaTic Lipid COntent in HUMANS a Randomized, Controlled, Double Blinded Trial
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.
Panoramica dello studio
Stato
Condizioni
Tipo di studio
Iscrizione (Effettivo)
Fase
- Fase 2
Contatti e Sedi
Luoghi di studio
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Vienna, Austria, 1090
- Medical University of Vienna, Department of Internal Medicine III
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
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].
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Scienza basilare
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Quadruplicare
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
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Comparatore placebo: Insulin dilution buffer
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 (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
Altri nomi:
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.
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Comparatore attivo: Intranasal Insulin administration
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. |
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.
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
Altri nomi:
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
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Changes in total lipid content in the liver
Lasso di tempo: one week before & at baseline & 1,2,3 and 4 weeks after intranasal insulin administration
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1H magnetic resonance spectroscopy
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one week before & at baseline & 1,2,3 and 4 weeks after intranasal insulin administration
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Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
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Changes of hepatic Lipid composition
Lasso di tempo: one week before & baseline & 1,2,3 and 4 weeks after intranasal insulin administration
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1H magnetic resonance spectroscopy
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one week before & baseline & 1,2,3 and 4 weeks after intranasal insulin administration
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Changes of myocardial lipid content
Lasso di tempo: baseline, 2 and 4 weeks after intranasal insulin administration
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1H magnetic resonance spectroscopy
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baseline, 2 and 4 weeks after intranasal insulin administration
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Changes of myocardial lipid composition
Lasso di tempo: baseline, 2 and 4 weeks after intranasal insulin administration
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1H magnetic resonance spectroscopy
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baseline, 2 and 4 weeks after intranasal insulin administration
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Changes of skeletal muscle lipid content
Lasso di tempo: baseline, 2 and 4 weeks after intranasal insulin administration
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1H magnetic resonance spectroscopy
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baseline, 2 and 4 weeks after intranasal insulin administration
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Changes of lipid composition in skeletal muscle
Lasso di tempo: baseline, 2 and 4 weeks after intranasal insulin administration
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1H magnetic resonance spectroscopy
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baseline, 2 and 4 weeks after intranasal insulin administration
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changes in heart function
Lasso di tempo: baseline, 2 and 4 weeks after intranasal insulin administration
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magnetic resonance imaging
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baseline, 2 and 4 weeks after intranasal insulin administration
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Altre misure di risultato
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
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Changes of parameters of glucose and lipid metabolism
Lasso di tempo: one week before & baseline & 1,2,3 and 4 weeks after initiation of intranasal insulin administration
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fasting Glucose, HbA1c, Cholesterol, LDL, HDL, TGs, non-HDL Cholesterol, FFAs
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one week before & baseline & 1,2,3 and 4 weeks after initiation of intranasal insulin administration
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Lipid composition in plasma
Lasso di tempo: one week before & at baseline & 1,2,3 and 4 weeks after intranasal insulin administration
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one week before & at baseline & 1,2,3 and 4 weeks after intranasal insulin administration
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Collaboratori e investigatori
Sponsor
Investigatori
- Investigatore principale: Michael Krebs, MD, Prof., Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria
Studiare le date dei record
Studia le date principali
Inizio studio
Completamento primario (Effettivo)
Completamento dello studio (Anticipato)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Stima)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Stima)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Termini MeSH pertinenti aggiuntivi
Altri numeri di identificazione dello studio
- INTO_humans
- 2013-004463-32 (Numero EudraCT)
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