HypoglycemiaEarly Phase 1NCT06470295
Effect of C-peptide on Hypoglycemic Counterregulation
A Early Phase 1 study testing Saline and C-peptide in people with Hypoglycemia and Type 1 Diabetes, run by University of Cincinnati at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Hypoglycemia, Type 1 Diabetes
- What is being tested?
- Saline and C-peptide
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 38 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jun 2024to 1 Jan 2028
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- BMI less than 30 kg/m2
Who cannot join
- pregnant or lactating women cigarette smoking presence of HIV or hepatitis presence of cardiovascular disease presence of microvascular disease
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Cincinnati
Cincinnati, Ohio, 45267-0547
Jason Winnick, PhD, 513-558-4437, jason.winnick@uc.edu
Natalie Whitsett, whitsenh@ucmail.uc.edu
About this study
Official title: 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.
Read the 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.
- Conditions
- Hypoglycemia, Type 1 Diabetes
- Being tested
- Saline, C-peptide
- Keywords
- glucagon, hepatic glucose production, C-peptide
- Medical subject headings
- Hypoglycemia, Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SalineOther
Normal saline will be infused during insulin-induced hypoglycemia
C-peptideBiological
C-peptide will be infused during insulin-induced hypoglycemia
| Study group | Role | What they receive |
|---|---|---|
| Healthy Control- Saline | Placebo comparator | Saline will be infused in healthy control subjects during insulin-induced hypoglycemia Receives: Other: Saline |
| Healthy Control- C-peptide | Active comparator | C-peptide will be infused in healthy control subjects during insulin-induced hypoglycemia Receives: Biological: C-peptide |
| T1D- Saline | Placebo comparator | Saline will be infused in T1D subjects during insulin-induced hypoglycemia Receives: Other: Saline |
| T1D- C-peptide | Active comparator | C-peptide will be infused in T1D subjects during insulin-induced hypoglycemia Receives: Biological: C-peptide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Glucagon
from plasma
Measured: During procedure, up to 2.5 hours
Secondary outcomes (2)
Hepatic glucose production
from plasma
Measured: During procedure, up to 2.5 hours
Liver glycogen
from MRS measurement
Measured: Prior to insulin-induced hypoglycemia
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2024
- Study start1 Jun 2024
- Primary completion1 Jun 2027 (estimated)
- Study completion1 Jan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HypoglycemiaStudies of the same condition, open and under way.
- More trials run by University of CincinnatiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- 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.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 38 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Cincinnati
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jason Winnick, University of Cincinnati
- Investigators
- Jason Winnick, PhD, Principal investigator, University of Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06470295
- Sponsor's protocol ID
- 2022-0236
- Status last verified
- Aug 2025
- First submitted
- 17 Jun 2024
- Last updated
- 17 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 37166980
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- On the Regulation of Hepatic Glucose Metabolism During Insulin-induced Hypoglycemia
- ClinicalTrials.gov ID
- NCT06470295
- Acronym / sponsor ID
- 2022-0236
- Conditions
- Hypoglycemia, Type 1 Diabetes
- Keywords
- glucagon, hepatic glucose production, C-peptide
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 38 participants (estimated)
- Lead sponsor
- University of CincinnatiUniversity, hospital or other
- Study start
- 1 Jun 2024 (actual)
- Primary completion
- 1 Jun 2027 (estimated)
- Study completion
- 1 Jan 2028 (estimated)
- First posted
- 24 Jun 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Healthy Control- Saline | Placebo comparator | Other: SalineSaline will be infused in healthy control subjects during insulin-induced hypoglycemia |
| Healthy Control- C-peptide | Active comparator | Biological: C-peptideC-peptide will be infused in healthy control subjects during insulin-induced hypoglycemia |
| T1D- Saline | Placebo comparator | Other: SalineSaline will be infused in T1D subjects during insulin-induced hypoglycemia |
| T1D- C-peptide | Active comparator | Biological: C-peptideC-peptide will be infused in T1D subjects during insulin-induced hypoglycemia |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- BMI less than 30 kg/m2
Key exclusion criteria (1 listed)
- pregnant or lactating women cigarette smoking presence of HIV or hepatitis presence of cardiovascular disease presence of microvascular disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SalineNormal saline will be infused during insulin-induced hypoglycemia | Other | Healthy Control- Saline, T1D- Saline |
| C-peptideC-peptide will be infused during insulin-induced hypoglycemia | Biological | Healthy Control- C-peptide, T1D- C-peptide |
Primary outcome
Glucagon
Time frame: During procedure, up to 2.5 hours
from plasma
2 secondary outcomes
Hepatic glucose production
Time frame: During procedure, up to 2.5 hours
Liver glycogen
Time frame: Prior to insulin-induced hypoglycemia
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2026.
- Results publication: PubMed 37166980Warner 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.
- Link to published paperLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jason Winnick, PhD principal investigator
University of Cincinnati
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Saline and C-peptide in people with Hypoglycemia and Type 1 Diabetes, run by University of Cincinnati at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 17 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jason Winnick, PhD (513-558-4437, jason.winnick@uc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Glucagon (time frame: During procedure, up to 2.5 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06470295, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Feb 2026.