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.
Studienübersicht
Status
Bedingungen
Studientyp
Einschreibung (Tatsächlich)
Phase
- Phase 2
Kontakte und Standorte
Studienorte
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Vienna, Österreich, 1090
- Medical University of Vienna, Department of Internal Medicine III
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Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Beschreibung
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].
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Grundlegende Wissenschaft
- Zuteilung: Zufällig
- Interventionsmodell: Parallele Zuordnung
- Maskierung: Vervierfachen
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
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Placebo-Komparator: 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
Andere Namen:
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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Aktiver Komparator: 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
Andere Namen:
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Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
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Changes in total lipid content in the liver
Zeitfenster: 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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Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
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Changes of hepatic Lipid composition
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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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Andere Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
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Changes of parameters of glucose and lipid metabolism
Zeitfenster: 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
Zeitfenster: 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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Mitarbeiter und Ermittler
Sponsor
Ermittler
- Hauptermittler: Michael Krebs, MD, Prof., Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn
Primärer Abschluss (Tatsächlich)
Studienabschluss (Voraussichtlich)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Schätzen)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Schätzen)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Zusätzliche relevante MeSH-Bedingungen
Andere Studien-ID-Nummern
- INTO_humans
- 2013-004463-32 (EudraCT-Nummer)
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