Effect of C-peptide on Hypoglycemic Counterregulation

February 13, 2026 updated by: Jason Winnick, University of Cincinnati

On the Regulation of Hepatic Glucose Metabolism During Insulin-induced Hypoglycemia

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Iatrogenic hypoglycemia is recognized as a primary barrier to the safe, effective management of blood glucose in people with type 1 diabetes (T1D). In previous experiments in the dog, we observed that C-peptide infusion augmented glucagon secretion and hepatic glucose production during insulin-induced hypoglycemia. The proposed experiments will determine the translational impact of this finding in patients with and without T1D.

Specific Aim #1 is to determine, in healthy control subjects, the effect of C-peptide co-infusion with insulin on endogenous glucose production (EGP) and counterregulatory hormone levels during hypoglycemia. This will be addressed by studying a single group of healthy subjects two times. In both studies, hypoglycemia will be induced with an intravenous (IV) infusion of insulin. During one study, C-peptide will be infused during the hypoglycemic period, and in the other study, saline will be infused. EGP is our primary variable, with secondary analyses including counterregulatory hormones and metabolic substrates.

Specific Aim #2 is to determine, in T1D patients, the effect of C-peptide co-infusion with insulin on EGP and counterregulatory hormone levels during hypoglycemia. The research plan for this Aim is very similar to that of Aim #1, with the main exception being that we will study T1D patients instead of healthy controls (e.g., two hypoglycemic clamp studies where C-peptide is administered during one study and saline during the other). In addition, the glycemic levels of these T1D patients will be monitored for 10 days prior to this visit to ensure that they do not experience hypoglycemia which could confound the data for the metabolic studies. Similar to Aim #1, EGP is our primary outcome variable, with secondary analyses including hormone and substrate levels.

Study Type

Interventional

Enrollment (Estimated)

38

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • BMI less than 30 kg/m2

Exclusion Criteria:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Healthy Control- Saline
Saline will be infused in healthy control subjects during insulin-induced hypoglycemia
Other: Saline
Normal saline will be infused during insulin-induced hypoglycemia
Active Comparator: Healthy Control- C-peptide
C-peptide will be infused in healthy control subjects during insulin-induced hypoglycemia
Biological: C-peptide
C-peptide will be infused during insulin-induced hypoglycemia
Placebo Comparator: T1D- Saline
Saline will be infused in T1D subjects during insulin-induced hypoglycemia
Other: Saline
Normal saline will be infused during insulin-induced hypoglycemia
Active Comparator: T1D- C-peptide
C-peptide will be infused in T1D subjects during insulin-induced hypoglycemia
Biological: C-peptide
C-peptide will be infused during insulin-induced hypoglycemia

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Glucagon
Time Frame: During procedure, up to 2.5 hours
from plasma
During procedure, up to 2.5 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hepatic glucose production
Time Frame: During procedure, up to 2.5 hours
from plasma
During procedure, up to 2.5 hours
Liver glycogen
Time Frame: Prior to insulin-induced hypoglycemia
from MRS measurement
Prior to insulin-induced hypoglycemia

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Cincinnati

Investigators

  • Principal Investigator: Jason Winnick, PhD, University of Cincinnati

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2024

Primary Completion (Estimated)

June 1, 2027

Study Completion (Estimated)

January 1, 2028

Study Registration Dates

First Submitted

June 17, 2024

First Submitted That Met QC Criteria

June 17, 2024

First Posted (Actual)

June 24, 2024

Study Record Updates

Last Update Posted (Actual)

February 17, 2026

Last Update Submitted That Met QC Criteria

February 13, 2026

Last Verified

August 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2022-0236

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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