HealthyPhase 3NCT04459338
A Dose-response Study Examining the Contribution of GLP-1 Receptor Signaling to Glucagon-stimulated Insulin Secretion
A Phase 3 study testing Exendin-9,39 and Saline in people with Healthy, run by Adrian Vella at 1 site in United States.
Trial summary
The GLP-1 receptor (GLP1R) gene is found on the beta cells of the pancreas. Its role is in the control of blood sugar level by enhancing insulin secretion from the pancreas after eating a meal. The purpose of this research study is to evaluate the role of GLP1R in the response to elevated glucagon concentrations. Read more about this study
- Who is it for?
- Ages 25 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Exendin-9,39 and Saline
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Mar 2021to 14 Jun 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 25 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 20 weight-stable, non-diabetic subjects
Who cannot join
- Age < 25 or > 65 years (to avoid studying subjects who could have latent type 1 diabetes, or the effects of age extremes in subjects with normal or impaired fasting glucose).
- HbA1c ≥5.9%
- Use of glucose-lowering agents.
- For female subjects: positive pregnancy test at the time of enrollment or study
- History of prior upper abdominal surgery such as adjustable gastric banding, pyloroplasty and vagotomy.
- Active systemic illness or malignancy.
- Symptomatic macrovascular or microvascular disease.
Trial locations and contacts
1 site in 1 country.
United States1 site
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
About this study
The GLP-1 receptor (GLP1R) gene is found on the beta cells of the pancreas. Its role is in the control of blood sugar level by enhancing insulin secretion from the pancreas after eating a meal. The purpose of this research study is to evaluate the role of GLP1R in the response to elevated glucagon concentrations.
Read the detailed description
Glucagon within the islet can signal the β-cell through GLP1R, and acts as an insulin secretagogue. This signaling is blocked by exendin-9,39. The relative importance of glucagon signaling through its cognate receptor or through GLP1R is unknown. Despite the lower affinity of GLP1R for glucagon, intra-islet concentrations of glucagon are sufficiently high to stimulate GLP1R. The other situation where this may occur is in response to pharmacologic doses of glucagon as used for β-cell function testing or raising peripheral glucagon concentrations above fasting values. The experiments proposed will characterize the role of GLP1R in glucagon's actions on the β-cell and the potential therapeutic role of dual (GLP-1R and glucagon receptor) agonists for the treatment of T2DM and obesity.
- Conditions
- Healthy
- Being tested
- Exendin-9,39, Saline
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Exendin-9,39Biological
Exendin-9,39 is a competitive antagonist of GLP-1 actions at the GLP-1 receptor
SalineOther
Placebo comparator
| Study group | Role | What they receive |
|---|---|---|
| Saline, Then Exendin-9,39 | Experimental | A week or two after screening, participants were admitted to the CRTU and Saline was infused during a hyperglycemic clamp during which escalating doses of glucagon were infused. After completion of this study participants underwent a washout period of 2 weeks after which they were readmitted to the CRTU and Exendin-9,39 was infused at 300pmol/kg/min was infused during a hyperglycemic clamp during which escalating doses of glucagon were infused. Receives: Biological: Exendin-9,39; Other: Saline |
| Exendin-9,39, Then Saline | Experimental | A week or two after screening, participants were admitted to the CRTU and Exendin-9,39 was infused at 300pmol/kg/min during a hyperglycemic clamp during which escalating doses of glucagon were infused. After completion of this study participants underwent a washout period of 2 weeks after which they were readmitted to the CRTU and Saline was infused during a hyperglycemic clamp during which escalating doses of glucagon were infused. Receives: Biological: Exendin-9,39; Other: Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Insulin Secretion Rate During Exendin-9,39 Infusion vs. Insulin Secretion Rate During Saline Infusion
This is the area under the curve for insulin secretion over the duration of the hyperglycemic clamp (0 to 300 minutes during the study in the Clinical Research Unit).
Measured: Area under the curve was quantified at the end of the Saline Study and at the end of the Exendin-9,39 study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jul 2020
- Study start4 Mar 2021
- Primary completion14 Jun 2022
- Study completion14 Jun 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HealthyStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Adrian Vella
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Adrian Vella, Mayo Clinic
- Investigators
- Adrian Vella, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04459338
- Sponsor's protocol ID
- 20-003995
- Other IDs
- 5R01DK126206-03
- Status last verified
- Jun 2023
- First submitted
- 30 Jun 2020
- Last updated
- 9 Jun 2023
- Results posted
- Yes, on ClinicalTrials.gov
- 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 9 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Dose-response Study Examining the Contribution of GLP-1 Receptor Signaling to Glucagon-stimulated Insulin Secretion
- ClinicalTrials.gov ID
- NCT04459338
- Acronym / sponsor ID
- 20-003995
- Conditions
- Healthy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Adrian VellaUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 4 Mar 2021 (actual)
- Primary completion
- 14 Jun 2022 (actual)
- Study completion
- 14 Jun 2022 (actual)
- First posted
- 7 Jul 2020 (actual)
- Results
- Posted 9 Jun 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The GLP-1 receptor (GLP1R) gene is found on the beta cells of the pancreas. Its role is in the control of blood sugar level by enhancing insulin secretion from the pancreas after eating a meal. The purpose of this research study is to evaluate the role of GLP1R in the response to elevated glucagon concentrations.
Detailed description
Glucagon within the islet can signal the β-cell through GLP1R, and acts as an insulin secretagogue. This signaling is blocked by exendin-9,39. The relative importance of glucagon signaling through its cognate receptor or through GLP1R is unknown. Despite the lower affinity of GLP1R for glucagon, intra-islet concentrations of glucagon are sufficiently high to stimulate GLP1R. The other situation where this may occur is in response to pharmacologic doses of glucagon as used for β-cell function testing or raising peripheral glucagon concentrations above fasting values. The experiments proposed will characterize the role of GLP1R in glucagon's actions on the β-cell and the potential therapeutic role of dual (GLP-1R and glucagon receptor) agonists for the treatment of T2DM and obesity.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Saline, Then Exendin-9,39 | Experimental | Biological: Exendin-9,39, Other: SalineA week or two after screening, participants were admitted to the CRTU and Saline was infused during a hyperglycemic clamp during which escalating doses of glucagon were infused. After completion of this study participants underwent a washout period of 2 weeks after which they were readmitted to the CRTU and Exendin-9,39 was infused at 300pmol/kg/min was infused during a hyperglycemic clamp during which escalating doses of glucagon were infused. |
| Exendin-9,39, Then Saline | Experimental | Biological: Exendin-9,39, Other: SalineA week or two after screening, participants were admitted to the CRTU and Exendin-9,39 was infused at 300pmol/kg/min during a hyperglycemic clamp during which escalating doses of glucagon were infused. After completion of this study participants underwent a washout period of 2 weeks after which they were readmitted to the CRTU and Saline was infused during a hyperglycemic clamp during which escalating doses of glucagon were infused. |
Who may qualify
- Ages
- 25 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 20 weight-stable, non-diabetic subjects
Key exclusion criteria (7 listed)
- Age < 25 or > 65 years (to avoid studying subjects who could have latent type 1 diabetes, or the effects of age extremes in subjects with normal or impaired fasting glucose).
- HbA1c ≥5.9%
- Use of glucose-lowering agents.
- For female subjects: positive pregnancy test at the time of enrollment or study
- History of prior upper abdominal surgery such as adjustable gastric banding, pyloroplasty and vagotomy.
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 |
|---|---|---|
| Exendin-9,39Exendin-9,39 is a competitive antagonist of GLP-1 actions at the GLP-1 receptor | Biological | Exendin-9,39, Then Saline, Saline, Then Exendin-9,39 |
| SalinePlacebo comparator | Other | Exendin-9,39, Then Saline, Saline, Then Exendin-9,39 |
Primary outcome
Insulin Secretion Rate During Exendin-9,39 Infusion vs. Insulin Secretion Rate During Saline Infusion
Time frame: Area under the curve was quantified at the end of the Saline Study and at the end of the Exendin-9,39 study
This is the area under the curve for insulin secretion over the duration of the hyperglycemic clamp (0 to 300 minutes during the study in the Clinical Research Unit).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Mayo Clinic Clinical TrialsLink 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. This study is not recruiting at the moment.
Adrian Vella, MD principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Exendin-9,39 and Saline in people with Healthy, run by Adrian Vella 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 7 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: finished, as of the sponsor's last update on 9 Jun 2023. 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. 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?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Jun 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Insulin Secretion Rate During Exendin-9,39 Infusion vs. Insulin Secretion Rate During Saline Infusion (time frame: Area under the curve was quantified at the end of the Saline Study and at the end of the Exendin-9,39 study). 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 9 Jun 2023.