Regulation of Endogenous Glucose Production by Brain Insulin Action in

Status Completed

Clinical Trial Summary

It is well known that the hormone insulin lowers blood glucose in part by acting directly on the liver and reducing hepatic glucose production. Animal studies have shown that the hormone insulin can act on the brain to indirectly lower glucose production by the liver. It has previously been shown that a nasal spray can deliver insulin directly to the brain without affecting circulating insulin concentration in humans. Intranasal spray of insulin suppressed hepatic glucose production in lean subjects. It is unknown whether this effects is blunted in subjects with insulin resistance.

Clinical Trial Description

Each study participant will be admitted to hospital the evening prior to the study. Following admission each study participant will be provided with a standardized dinner. At 7am (t=0) the next day we will begin a primed, constant intravenous infusion d2 glucose (a stable isotope of glucose, the enrichment of which can be measured by gas chromatography mass spectrometry, allowing us to calculate endogenous glucose production rates) and continue this for 8 hours. At the same time (7am) a pancreatic clamp will be started as described above for 8 hours. Blood samples will be analysed with a glucometer for instant blood glucose readings At 9 am (+120 minutes) intranasal placebo or insulin will be administered. The insulin (Humalog Lispro 100 IU/ml, Eli Lily, Canada) and placebo (diluent) will be transferred to a metered nasal device (Pharmasystems, Ontario #063636 802721, Item 10271) immediately prior to use. This device dispenses 0.1ml (10 IU) per puff. 4 x 0.1 ml puffs/vials (2 per nostril) will be administered at rate of 2 (one in each nostril) every 60 seconds. Blood will be drawn at t=0, 30, 60, 120 and every 10 minutes thereafter for 6 hours. In order to match peripheral lispro concentrations between study visits, a small dose of Humalog (lispro) insulin will be administered intravenously at 9am, during the placebo arm of the study. Based on the pharmacokinetics of Humalog lispro (personal communication from Eli Lilly), we propose to administer 0.005 IU/kg over 30 minutes. 20% dextrose will be administered to maintain euglycemia as necessary. Insulin, glucagon, and glucose isotopic enrichment will be measured. The enrichment data and glucose infusion will be used to calculate steady state glucose production. ;

Study Design

Related Conditions & MeSH terms

Insulin Resistance

Clinical Trial Details

NCT number	NCT03383822
Study type	Interventional
Source	University Health Network, Toronto
Contact
Status	Completed
Phase	Phase 1/Phase 2
Start date	September 8, 2015
Completion date	December 1, 2017

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Clinical trials are conducted in a series of steps, called phases - each phase is designed to answer a separate research question.

Phase 1: Researchers test a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
Phase 2: The drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety.
Phase 3: The drug or treatment is given to large groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
Phase 4: Studies are done after the drug or treatment has been marketed to gather information on the drug's effect in various populations and any side effects associated with long-term use.

Regulation of Endogenous Glucose Production by Brain Insulin Action in Insulin Resistance — NI EGP highBMI

Clinical Trial Summary

Clinical Trial Description

Study Design

Related Conditions & MeSH terms