Assessment of Intranasal Glucagon on Endogenous Glucose Production

NCT02740829 | Completed Phase 1

• 1 other identifier: REB 14-8171-A
• Study Type: interventional
• Target: 10
• Locations: 0 countries
• Sites: N/A

Brief Summary

Peripheral glucagon action increases hepatic glucose production. In rodents hypothalamic action of glucagon paradoxically suppresses glucose production. Intranasally administered peptides have been shown to preferentially enter the central nervous system. We assessed the effects of intranasal glucagon on hepatic glucose production

Conditions

Diabetes

Outcome Measures

Primary Outcomes (1)

• Endogenous glucose production following intranasal glucagon compared to placebo

  Stable isotope infusion (D2 glucose) will enable assessment of endogenous glucose production by measuring glucose enrichment in plasma by gas chromatogaphy mass spectrometry. During steady state, rate of glucose appearance (Ra) = rate of glucose disappearance (Rd), where Ra = tracer infusion rate /plasma tracer enrichment. Endogenous glucose production (EGP) rate = Ra - glucose infusion rate

  6 hours

Study Arms (2)

Intranasal placebo

PLACEBO COMPARATOR

placebo comparator

Drug: Intranasal placebo

Intranasal glucagon

EXPERIMENTAL

active intervention

Drug: Intranasal glucagon

Interventions

Intranasal glucagon DRUG

Glucagon will be administered via a nasal dispenser

Intranasal glucagon

Intranasal placebo DRUG

Placebo

Intranasal placebo

Eligibility Criteria

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

You may qualify if:

• \. Men and women, aged 18 to 60 years 2. Body mass index 20 to 27 kg/m2 3. Hemoglobin in the normal range. 4. Normal glucose tolerance in response to a 75gram glucose

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 4. Any significant active (over the past 12 months) disease of the gastrointestinal, pulmonary, neurological, renal, genitourinary, hematological systems, or has severe uncontrolled treated or untreated hyper/ hypotension (sitting diastolic \> 100 or systolic \> 180 or systolic\<100) or proliferative retinopathy 5. Use of immunosuppressive agents at any time during the study 6. Allergy to any study medication 7. Pregnancy or breastfeeding 8. Heavy smoker 9. Fasting blood glucose \> 6.0 mmol/l or known diabetes. 10. Any history of a MI or clinically significant, active, cardiovascular history including a history of arrhythmia's or conduction delays on ECG, unstable angina, or decompensated heart failure.
• \. Any nasal pathology. 12. Abnormal liver and thyroid function 13. Current addiction to alcohol or substances of abuse as determined by the investigator or of any mental illness.
• \. Mental incapacity, unwillingness or language barrier precluding adequate understanding or cooperation 15. Taking any regular prescription or non-prescription medications at the time of the study. Occasional use of medications such as acetoaminophen or Tylenol 1 or any use of natural health products may be permitted at the discretion of the investigator.
• \. Will not donate blood three months prior to and three months post study procedures

Sponsors & Collaborators

• University Health Network, Toronto: lead

Related Publications (1)

• Dash S, Xiao C, Stahel P, Koulajian K, Giacca A, Lewis GF. Evaluation of the specific effects of intranasal glucagon on glucose production and lipid concentration in healthy men during a pancreatic clamp. Diabetes Obes Metab. 2018 Feb;20(2):328-334. doi: 10.1111/dom.13069. Epub 2017 Sep 14.

  PMID: 28730676 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Design

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

Study Record Dates

• First Submitted: March 8, 2016
• First Posted: April 15, 2016
• Study Start: March 1, 2015
• Primary Completion: January 1, 2016
• Study Completion: March 1, 2016
• Last Updated: April 15, 2016

Record last verified: 2016-04

Data Sharing

• IPD Sharing: Will not share