Regulation of Endogenous Glucose Production by Brain Insulin Action in Insulin Resistance

NCT03383822 | Completed Phase 1

• 1 other identifier: NI EGP highBMI 12-5032A
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Insulin Resistance

Outcome Measures

Primary Outcomes (1)

• Endogenous glucose production

  Effects of intranasal insulin and placebo on endogenous glucose production will be assessed

  8 hours

Study Arms (2)

Intranasal insulin

EXPERIMENTAL

40 IU of intranasal insulin

Drug: Intranasal insulin

Intranasal placebo

PLACEBO COMPARATOR

Placebo comparator to intranasal insulin

Drug: Intranasal placebo

Interventions

Intranasal insulin DRUG

Humalog lispro 40 IU intranasally

Also known as: Insulin

Intranasal insulin

Intranasal placebo DRUG

Diluent intranasally

Also known as: Placebo

Intranasal placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Men and women, aged 18 to 60 years
• Body mass index \>30 kg/m2
• Hemoglobin in the normal range.
• Normal glucose tolerance in response to a 75g, 2-hr oral glucose tolerance test
• Women of reproductive age should be on contraception (oral contraceptive pill or intra-uterine device/coil) for at least 2 months prior to and after the study.

You may not qualify if:

• Study participant with a history of hepatitis/hepatic disease that has been active within the previous two years.
• Any current or previous history of biliary disease (including gall stones, biliary atresia and cholecystitis) or pancreatitis.
• Any current or previous history of endocrine disease, dyslipidemia or malignancy
• Any significant active (over the past 12 months) disease of the gastrointestinal, pulmonary, neurological, renal (Cr \> 1.5 mg/dL) genitourinary, hematological systems, or has severe uncontrolled treated or untreated hyper/ hypotension (sitting diastolic BP \> 100 or systolic \> 180 or systolic BP\<100) or proliferative retinopathy
• Use of immunosuppressive agents at any time during the study
• Allergy to any study medication
• Pregnancy or breastfeeding
• Heavy smoker
• Prior nasoduodenal tube insertion under fluoroscopic guidance.
• Fasting blood glucose \> 6.0 mmol/l or known diabetes.
• Any history of a myocardial infarction or clinically significant, active, cardiovascular history including a history of arrhythmia's or conduction delays on electrocardiogram, unstable angina, or decompensated heart failure.
• Any nasal pathology likely to affect absorption of insulin or insertion of nasoduodenal tube.
• Any laboratory values: aspartate transaminase \> 2x upper limit of normal; alanine aminotransferase \> 2x upper limit of normal; thyroid-stimulating hormone \> 6 micro unit/l
• Current addiction to alcohol or substances of abuse as determined by the investigator.
• Mental incapacity, unwillingness or language barrier precluding adequate understanding or cooperation

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

Tornto General Hospital, UHN

Toronto, Ontario, M5G 1L7, Canada

Location

MeSH Terms

Conditions

Insulin Resistance

Interventions

Insulin

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2017
• First Posted: December 26, 2017
• Study Start: September 8, 2015
• Primary Completion: July 31, 2017
• Study Completion: December 1, 2017
• Last Updated: December 26, 2017

Record last verified: 2017-12

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)