Diabetes (DM)Phase 1/2SIGNALNCT07300982
Studies of Insulin and Glucagon Action in the Liver
A Phase 1/2 study testing Glucagon in people with Diabetes (DM), run by Duke University at 1 site in United States.
Trial summary
This study examines how glucagon works to regulate glucose metabolism, based on new findings that suggest glucagon signaling in the liver has more than one role, and that these multiple roles can be opposing in nature. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Diabetes (DM)
- What is being tested?
- Glucagon
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2026to Dec 2029
- Phase
- Phase 1/2
- 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 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy adults age 18-45 years
- Body Mass Index (BMI) < 27.0 kg/m²
- Fasting plasma glucose ≤ 95 mg/dL or HbA1c ≤ 5.8% as measured at screening visit
Who cannot join
- Active medical disease: e.g. active infectious, inflammatory, neurodegenerative or mental health disorders
- No personal history of diabetes or pancreatitis
- No personal history of cardiac, gastrointestinal, renal or liver disease
- No history of diabetes among any first-degree family members
- Renal insufficiency (eGFR < 60 mL/kg/min)
- Anemia (hematocrit < 34%) as measured at screening visit
- Pregnant females
- Consumption of daily medications that alter glucose metabolism of GI function (glucocorticoids, psychotropics, narcotics, metoclopramide)
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
Duke Center for Living
Durham, North Carolina, 27705
Johanna Johnson, MS, 919-660-6766, johanna.johnson@duke.edu
Alyssa Sudnick, MS, 919-660-6769, alyssa.sudnick@duke.edu
About this study
This study examines how glucagon works to regulate glucose metabolism, based on new findings that suggest glucagon signaling in the liver has more than one role, and that these multiple roles can be opposing in nature. Understanding this biology provides an opportunity to develop new generations of glucagon-based drugs that target specific pathways, making them more effective at controlling blood glucose.
Participants will complete paired, 5-hour hyperinsulinemic glucose clamp visits in which they receive either glucagon or saline infusions while blood glucose is maintained and frequent blood samples are collected. The primary focus is whether coordinated glucagon and insulin signaling enhances hepatic insulin sensitivity.
Read the detailed description
Volunteers will undergo screening for medical history, medication usage, and blood work; those who qualify will be offered participation. Study participation will last approximately 5-12 weeks depending on appointment availability and the number of infusions planned. This protocol involves two sets of paired procedures. Approximately 15 participants will complete each set of paired visits. Participants can opt to complete one set of paired visits or both sets of paired visits.
Set 1: Each participant will complete two 5-hour hyperinsulinemic clamp procedures to examine the effects of glucagon on glucose metabolism while measuring systemic glucose turnover and related blood markers. The procedures will be identical, except for the final phase of the procedure when either saline or a stepwise glucagon infusion will be administered.
Set 2: Each participant will complete two 5-hour hyperinsulinemic clamp procedures to examine the effects of insulin on glucose metabolism while measuring systemic glucose turnover and related blood markers. The procedures will be identical, except for the final phase of the procedure when either saline or a steady glucagon infusion will be administered.
- Conditions
- Diabetes (DM)
- Being tested
- Glucagon, Saline (placebo)
- Keywords
- Glucose metabolism, Hepatic insulin sensitivity, Glucagon, Insulin, hepatic glucose production
- Medical subject headings
- Diabetes Mellitus, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GlucagonDrug
Glucagon infusion either graded (0.2→0.4→0.6 ng/kg/min) or continuous (0.4 ng/kg/min) during the final 90 minutes of a hyperinsulinemic glucose clamp. The graded or continuous glucagon infusions are given as a component of 2 separate protocols. Glucagon prepared per pharmacy/bedside protocol.
Saline (placebo)Drug
IV saline infusion during clamp for 90 minutes as control.
| Study group | Role | What they receive |
|---|---|---|
| Glucagon infusion during hyperinsulinemic clamp | Experimental | Glucagon infusion either graded (0.2→0.4→0.6 ng/kg/min) or continuous (0.4 ng/kg/min) during the final 90 minutes of a hyperinsulinemic glucose clamp. The graded or continuous glucagon infusions are given as a component of 2 separate protocols. Receives: Drug: Glucagon |
| Saline infusion during hyperinsulinemic clamp | Placebo comparator | Saline infusion during the final 90 minutes of an otherwise identical clamp procedure. Receives: Drug: Saline (placebo) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Glucose appearance (Ra)
Glucose appearance will be determined using steady state computations, unless a stable tracer:tracee ratio is not maintained
Measured: In these experiments outcomes will be based on measurements made in the final 90 minutes of the hyperinsulinemic glucose clamp.
Glucose disappearance (Rd)
Glucose disappearance (Rd) will be determined using steady state computations, unless a stable tracer:tracee ratio is not maintained
Measured: In the experiments described here glucose turnover (Ra and Rd) will be determined in the final 90 minutes of the hyperinsulinemic glucose clamp.
Hepatic insulin sensitivity
Hepatic insulin sensitivity will be calculated as EGP divided by insulin concentration
Measured: Basal period (time -30-0 min), after the insulin infusion alone (60-90 min), and during the glucagon/saline infusions (120-180 min)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2025
- Study startOct 2026 (estimated)
- Primary completionDec 2029 (estimated)
- Study completionDec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetes (DM)Studies of the same condition, open and under way.
- More trials run by Duke UniversityThe 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
- Phase 1/2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- The studies proposed here will focus on the hepatic interactions of insulin and glucagon using physiological concentrations of these two islet peptides. A group of healthy subjects will be studied on two occasions over 2 weeks in counterbalanced order (with and without glucagon) during a glucose clamp with a fixed dose of insulin. Hepatic glucoses production and glucose metabolism will be measured with stably labeled glucose tracers.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- David D'Alessio, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07300982
- Sponsor's protocol ID
- Pro00117291
- Other IDs
- R01DK141090
- Acronym
- SIGNAL
- Status last verified
- Aug 2026
- First submitted
- 22 Dec 2025
- Last updated
- 5 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Studies of Insulin and Glucagon Action in the Liver
- ClinicalTrials.gov ID
- NCT07300982
- Acronym / sponsor ID
- SIGNAL / Pro00117291
- Conditions
- Diabetes (DM)
- Keywords
- Glucose metabolism, Hepatic insulin sensitivity, Glucagon, Insulin, hepatic glucose production
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- Oct 2026 (estimated)
- Primary completion
- Dec 2029 (estimated)
- Study completion
- Dec 2029 (estimated)
- First posted
- 24 Dec 2025 (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.
This study examines how glucagon works to regulate glucose metabolism, based on new findings that suggest glucagon signaling in the liver has more than one role, and that these multiple roles can be opposing in nature. Understanding this biology provides an opportunity to develop new generations of glucagon-based drugs that target specific pathways, making them more effective at controlling blood glucose.
Participants will complete paired, 5-hour hyperinsulinemic glucose clamp visits in which they receive either glucagon or saline infusions while blood glucose is maintained and frequent blood samples are collected. The primary focus is whether coordinated glucagon and insulin signaling enhances hepatic insulin sensitivity.
Detailed description
Volunteers will undergo screening for medical history, medication usage, and blood work; those who qualify will be offered participation. Study participation will last approximately 5-12 weeks depending on appointment availability and the number of infusions planned. This protocol involves two sets of paired procedures. Approximately 15 participants will complete each set of paired visits. Participants can opt to complete one set of paired visits or both sets of paired visits.
Set 1: Each participant will complete two 5-hour hyperinsulinemic clamp procedures to examine the effects of glucagon on glucose metabolism while measuring systemic glucose turnover and related blood markers. The procedures will be identical, except for the final phase of the procedure when either saline or a stepwise glucagon infusion will be administered.
Set 2: Each participant will complete two 5-hour hyperinsulinemic clamp procedures to examine the effects of insulin on glucose metabolism while measuring systemic glucose turnover and related blood markers. The procedures will be identical, except for the final phase of the procedure when either saline or a steady glucagon infusion will be administered.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- The studies proposed here will focus on the hepatic interactions of insulin and glucagon using physiological concentrations of these two islet peptides. A group of healthy subjects will be studied on two occasions over 2 weeks in counterbalanced order (with and without glucagon) during a glucose clamp with a fixed dose of insulin. Hepatic glucoses production and glucose metabolism will be measured with stably labeled glucose tracers.
| Arm | Type | Receives |
|---|---|---|
| Glucagon infusion during hyperinsulinemic clamp | Experimental | Drug: GlucagonGlucagon infusion either graded (0.2→0.4→0.6 ng/kg/min) or continuous (0.4 ng/kg/min) during the final 90 minutes of a hyperinsulinemic glucose clamp. The graded or continuous glucagon infusions are given as a component of 2 separate protocols. |
| Saline infusion during hyperinsulinemic clamp | Placebo comparator | Drug: Saline (placebo)Saline infusion during the final 90 minutes of an otherwise identical clamp procedure. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Healthy adults age 18-45 years
- Body Mass Index (BMI) < 27.0 kg/m²
- Fasting plasma glucose ≤ 95 mg/dL or HbA1c ≤ 5.8% as measured at screening visit
Key exclusion criteria (8 listed)
- Active medical disease: e.g. active infectious, inflammatory, neurodegenerative or mental health disorders
- No personal history of diabetes or pancreatitis
- No personal history of cardiac, gastrointestinal, renal or liver disease
- No history of diabetes among any first-degree family members
- Renal insufficiency (eGFR < 60 mL/kg/min)
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 |
|---|---|---|
| GlucagonGlucagon infusion either graded (0.2→0.4→0.6 ng/kg/min) or continuous (0.4 ng/kg/min) during the final 90 minutes of a hyperinsulinemic glucose clamp. The graded or continuous glucagon infusions are given as a component of 2 separate protocols. Glucagon prepared per pharmacy/bedside protocol. | Drug | Glucagon infusion during hyperinsulinemic clamp |
| Saline (placebo)IV saline infusion during clamp for 90 minutes as control. | Drug | Saline infusion during hyperinsulinemic clamp |
Primary outcome
Glucose appearance (Ra)
Time frame: In these experiments outcomes will be based on measurements made in the final 90 minutes of the hyperinsulinemic glucose clamp.
Glucose appearance will be determined using steady state computations, unless a stable tracer:tracee ratio is not maintained
Glucose disappearance (Rd)
Time frame: In the experiments described here glucose turnover (Ra and Rd) will be determined in the final 90 minutes of the hyperinsulinemic glucose clamp.
Glucose disappearance (Rd) will be determined using steady state computations, unless a stable tracer:tracee ratio is not maintained
Hepatic insulin sensitivity
Time frame: Basal period (time -30-0 min), after the insulin infusion alone (60-90 min), and during the glucagon/saline infusions (120-180 min)
Hepatic insulin sensitivity will be calculated as EGP divided by insulin concentration
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 5 Aug 2026.
- 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.
David D'Alessio, MD principal investigator
Duke University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Glucagon in people with Diabetes (DM), run by Duke University 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 3 inclusion and 8 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: opening soon, as of the sponsor's last update on 5 Aug 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Johanna Johnson, MS (919-660-6766, johanna.johnson@duke.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Glucose appearance (Ra) (time frame: In these experiments outcomes will be based on measurements made in the final 90 minutes of the hyperinsulinemic glucose clamp.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Aug 2026.