The Effect of Glucagon on Rates of Hepatic Mitochondrial Oxidation in Man Assessed by PINTA

NCT03965130 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 0209020997_aMISP58340
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

It is well established that alterations in the portal vein insulin:glucagon ratio play a major role in the dysregulated hepatic glucose metabolism in type 2 diabetes but the molecular mechanism by which glucagon promotes alterations in hepatic glucose production and mitochondrial oxidation remain poorly understood. This is borne out of the fact that both glucagon agonists and antagonists are being developed to treat type 2 diabetes with unclear mechanisms of action. This study will directly assess rates of mitochondrial oxidation and pyruvate carboxylase flux for the first time in humans using PINTA analysis as well as the effects of glucagon. The results will have important implications for the possibility of intervening in the pathogenesis of non alcoholic fatty liver and type 2 diabetes via chronic dual GLP-1/glucagon receptor antagonism and provide an important rationale for why a dual agonist may be more efficacious for treatment of non alcoholic fatty liver and T2D than GLP-1 alone.

Conditions

Healthy Participants

Keywords

Hepatic Glucose Metabolism; Hepatic Mitochondrial Oxidation; PINTA; Glucagon

Outcome Measures

Primary Outcomes (1)

• Rates of Hepatic Mitochondrial Oxidation

  Rates of pyruvate carboxylase flux and citrate synthesis flux will be assessed using GC/MS and NMR analyses of plasma glucose 13C enrichments after the \[3-13C\]lactate infusion

  5 hours

Study Arms (2)

Glucagon

EXPERIMENTAL

Participants will receive glucagon during the PINTA study

Biological: Glucagon

Control

EXPERIMENTAL

The same participants will not receive glucagon during the PINTA study

Other: Control Study

Interventions

Glucagon BIOLOGICAL

PINTA study with glucagon

Also known as: hormone study

Glucagon

Control Study OTHER

The same participants will not receive glucagon during the PINTA study

Also known as: No glucagon

Control

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy
• Non smoking
• Taking no medications except birth control

You may not qualify if:

• Any systemic or organ disease
• Smoking
• Taking any drug or medications other than birth control (women)

Sponsors & Collaborators

• Yale University: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Yale Hospital reserach Unit / YCCI

New Haven, Connecticut, 06520, United States

Location

MeSH Terms

Conditions

Pinta

Interventions

Glucagon

Condition Hierarchy (Ancestors)

Treponemal Infections; Spirochaetales Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Skin Diseases, Bacterial; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Kitt Falk Petersen
• Organization: Yale

kitt.petersen@yale.edu

203 737 1942

Study Officials

• Kitt F Petersen, MD

  Professor

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Each participant will participate in two studies: one without and one with a 3 hour infusion of glucagon during the PINTA study

Study Record Dates

• First Submitted: May 23, 2019
• First Posted: May 28, 2019
• Study Start: June 5, 2019
• Primary Completion: July 7, 2022
• Study Completion: July 6, 2023
• Last Updated: November 26, 2024
• Results First Posted: November 26, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)