Effect of C-peptide on Hypoglycemic Counterregulation

NCT ID: NCT06470295

Last Updated: 2025-08-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

EARLY_PHASE1

Total Enrollment

38 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-06-01

Study Completion Date

2028-01-01

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Hypoglycemia Type 1 Diabetes

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

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.
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

DOUBLE

Participants Investigators
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.

Study Groups

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Healthy Control- Saline

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

Group Type PLACEBO_COMPARATOR

Saline

Intervention Type OTHER

Normal saline will be infused during insulin-induced hypoglycemia

Healthy Control- C-peptide

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

Group Type ACTIVE_COMPARATOR

C-peptide

Intervention Type BIOLOGICAL

C-peptide will be infused during insulin-induced hypoglycemia

T1D- Saline

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

Group Type PLACEBO_COMPARATOR

Saline

Intervention Type OTHER

Normal saline will be infused during insulin-induced hypoglycemia

T1D- C-peptide

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

Group Type ACTIVE_COMPARATOR

C-peptide

Intervention Type BIOLOGICAL

C-peptide will be infused during insulin-induced hypoglycemia

Interventions

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Saline

Normal saline will be infused during insulin-induced hypoglycemia

Intervention Type OTHER

C-peptide

C-peptide will be infused during insulin-induced hypoglycemia

Intervention Type BIOLOGICAL

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

40 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Cincinnati

OTHER

Sponsor Role lead

Responsible Party

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Jason Winnick

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Jason Winnick, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Cincinnati

Locations

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University of Cincinnati

Cincinnati, Ohio, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Jason Winnick, PhD

Role: CONTACT

513-558-4437

Natalie Whitsett

Role: CONTACT

513-558-4489

Facility Contacts

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Jason Winnick, PhD

Role: primary

513-558-4437

Natalie Whitsett

Role: backup

References

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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.

Reference Type BACKGROUND
PMID: 37166980 (View on PubMed)

Related Links

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Other Identifiers

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2022-0236

Identifier Type: -

Identifier Source: org_study_id

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