Effect of C-peptide on Hypoglycemic Counterregulation

NCT06470295 | Recruiting Early Phase 1 FDA Drug

• 1 other identifier: 2022-0236
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

Iatrogenic hypoglycemia is the most prominent barrier to the safe, effective management of blood sugar in people with type 1 diabetes due to periodic over-insulinization. During insulin-induced hypoglycemia, glucagon secretion is diminished in type 1 diabetes which, in turn, reduces hepatic glucose production and increases the depth and duration of hypoglycemic episodes. We have observed that the naturally occurring protein C-peptide increases glucagon secretion in dogs during insulin-induced hypoglycemia, which increases hepatic glucose production; the experiments in this application will shed light on the translation of this finding to the human.

Conditions

Hypoglycemia; Type 1 Diabetes

Keywords

glucagon; hepatic glucose production; C-peptide

Outcome Measures

Primary Outcomes (1)

• Glucagon

  from plasma

  During procedure, up to 2.5 hours

Secondary Outcomes (2)

• Hepatic glucose production

  During procedure, up to 2.5 hours

• Liver glycogen

  Prior to insulin-induced hypoglycemia

Study Arms (4)

Healthy Control- Saline

PLACEBO COMPARATOR

Saline will be infused in healthy control subjects during insulin-induced hypoglycemia

Other: Saline

Healthy Control- C-peptide

ACTIVE COMPARATOR

C-peptide will be infused in healthy control subjects during insulin-induced hypoglycemia

Biological: C-peptide

T1D- Saline

PLACEBO COMPARATOR

Saline will be infused in T1D subjects during insulin-induced hypoglycemia

Other: Saline

T1D- C-peptide

ACTIVE COMPARATOR

C-peptide will be infused in T1D subjects during insulin-induced hypoglycemia

Biological: C-peptide

Interventions

Saline OTHER

Normal saline will be infused during insulin-induced hypoglycemia

Healthy Control- Saline; T1D- Saline

C-peptide BIOLOGICAL

C-peptide will be infused during insulin-induced hypoglycemia

Healthy Control- C-peptide; T1D- C-peptide

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• BMI less than 30 kg/m2

You may not qualify if:

• pregnant or lactating women cigarette smoking presence of HIV or hepatitis presence of cardiovascular disease presence of microvascular disease

Sponsors & Collaborators

• University of Cincinnati: lead

Study Sites (1)

University of Cincinnati

Cincinnati, Ohio, 45267-0547, United States

RECRUITING

Related Publications (1)

• Warner SO, Dai Y, Sheanon N, Yao MV, Cason RL, Arbabi S, Patel SB, Lindquist D, Winnick JJ. Short-term fasting lowers glucagon levels under euglycemic and hypoglycemic conditions in healthy humans. JCI Insight. 2023 Jun 22;8(12):e169789. doi: 10.1172/jci.insight.169789.

  PMID: 37166980 RESULT

Related Links

• Link to published paper

MeSH Terms

Conditions

Hypoglycemia; Diabetes Mellitus, Type 1

Interventions

Sodium Chloride; C-Peptide

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Diabetes Mellitus; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Jason Winnick, PhD

  University of Cincinnati

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jason Winnick, PhD

CONTACT

513-558-4437; jason.winnick@uc.edu

Natalie Whitsett

CONTACT

513-558-4489; whitsenh@ucmail.uc.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: During participation in these studies, the subject and the researchers will not know which treatment (C-peptide versus saline) was administered to the subject on what day until after that subject has completed the study.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Each subject will undergo two metabolic studies, one where they receive an IV infusion of C-peptide during insulin-induced hypoglycemia, and one where they will receive an IV infusion of saline instead.

Study Record Dates

• First Submitted: June 17, 2024
• First Posted: June 24, 2024
• Study Start: June 1, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): January 1, 2028
• Last Updated: February 17, 2026

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)