Insulin SecretionPhase 4NCT02844907
Regulation of Insulin Secretion by the GLP-1 Receptor
A Phase 4 study testing Exendin (9-39), Dexamethasone and Hyperglycemic Clamp in people with Insulin Secretion, run by VA Office of Research and Development at 1 site in United States.
Trial summary
AIM2: The purpose of Aim-2 of this study is to determine the role of basal GLP-1 action on the beta-cell response to insulin resistance. Healthy subjects will have fasting GLP-1 action determined with GLP-1r blockade before and after induction of experimental insulin resistance. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Insulin Secretion
- What is being tested?
- Exendin (9-39), Dexamethasone and Hyperglycemic Clamp
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jul 2018to 31 Dec 2021
- Phase
- Phase 4
- 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 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- AIM2: SELECTION OF HEALTHY SUBJECTS
- Healthy adults age 20-45 years
- Body Mass Index (BMI) less than or equal to 35.0 kg/m2
- HbA1c less than or equal to 5.7% as measured at screening visit
- Ability to speak and understand English
- AIM3: NON-DIABETIC SUBJECTS
Show all 16Show fewer
- Adults age 18-65 years
- Body Mass Index (BMI) 25-40.0 kg/m2
- HbA1c less than or equal to 6.5% as measured at screening visit
- No Diabetes or use of diabetes medications such as insulin or metformin
- Ability to speak and understand English
- AIM3: DIABETIC Type II SUBJECTS
- Adults age 18-65 years
- Body Mass Index (BMI) 25-40.0 kg/m2
- HbA1c less than or equal to 7.5% plus a diagnosis of Type II diabetes managed by either Metformin, Sulfonylurea, or diet and exercise
- Ability to speak and understand English
Who cannot join
- AIM2:
- Uncontrolled high blood pressure
- Diabetes or use of diabetes medications such as insulin or metformin
- Evidence of active heart disease, unstable angina or heart failure
- Lung disease or COPD
- Malabsorptive GI disease, such as celiac disease, or gastric bypass
Show all 29Show fewer
- Significant hepatic disease
- Kidney disease or renal insufficiency (eGFR < 60 mL/kg/min)
- Untreated anemia (hematocrit < 34%) as measured at screening visit
- Pregnant females
- Active substance abuse
- Chronic use of oral steroid medications such as prednisone and hydrocortisone
- Apparent sensitivity to any study peptides as determined by the skin test
- Diagnosis or h/o PTSD
- Active mental health disorders such as depression, or as a result of Traumatic Brain Injury (TBI)
- AIM3: ALL SUBJECTS
- Uncontrolled high blood pressure
- Evidence of active heart disease, unstable angina or heart failure
- Lung disease or COPD
- Malabsorptive GI disease, such as celiac disease, or gastric bypass
- Significant hepatic disease
- Kidney disease or renal insufficiency (eGFR < 60 mL/kg/min)
- Untreated anemia (hematocrit < 34%) as measured at screening visit
- Pregnant females
- Active substance abuse
- Chronic use of oral steroid medications such as prednisone and hydrocortisone
- Apparent sensitivity to any study peptides as determined by the skin test
- Diagnosis or h/o PTSD
- Active mental health disorders such as depression, or as a result of Traumatic Brain Injury (TBI)
Trial locations and contacts
1 site in 1 country.
United States1 site
Durham VA Medical Center, Durham, NC
Durham, North Carolina, 27705
About this study
AIM2: The purpose of Aim-2 of this study is to determine the role of basal GLP-1 action on the beta-cell response to insulin resistance. Healthy subjects will have fasting GLP-1 action determined with GLP-1r blockade before and after induction of experimental insulin resistance. The investigators hypothesize that fasting GLP-1 action will increase to compensate for experimental insulin resistance.
AIM3: The purpose of Aim-3 of this study is to determine the role of basal GLP-1 action on fasting glucose regulation in lean, obese, pre-diabetic and type 2 diabetic (T2DM) subjects. A cross sectional study of age-matched subjects across the spectrum of glucose tolerance will be used to test the hypothesis that fasting GLP-1 action increases as beta-cell function declines.
Read the detailed description
AIM2: The purpose of this study is to determine the role of basal GLP-1 action on the beta-cell response to insulin resistance. Healthy subjects will have fasting GLP-1 action determined with GLP-1r blockade before and after induction of experimental insulin resistance. The investigators hypothesize that fasting GLP-1 action will increase to compensate for experimental insulin resistance.
The study will enroll up to 20-25 healthy participants and while it is anticipated that the screening blood draw will yield a number of screen failures, it is estimated that 10-15 subjects will complete the entire study protocol. Enrolled participants will be asked to complete three study visits including the consent visit and two infusion study visits that will include hyperglycemic clamp procedures with the addition of the GLP-1 receptor antagonist Exendin (9-39) to determine the fasting GLP-1 effect. Each infusion procedure will last 2 hours. Subjects will be asked to take dexamethasone daily for approximately one week between Visit-2 and Visit-3 to induce insulin resistance.
The investigators will enroll 6-10 additional subjects as controls for effects of time and repeat testing. These individuals will have identical clamps with no dexamethasone at approximately 1 week intervals and will be determined at random by study staff.
The primary outcome for visits 2-3 will be to measure the effects of Ex-9 on fasting glucose-stimulated insulin secretion before and after experimentally induced insulin resistance. The primary experimental variable for analysis will be C-peptide during the clamp. Mean values will be compared between the period of glucose only stimulation and glucose with Ex-9. For each subject in the active treatment arm data will be analyzed using 2-way ANOVA for repeated measures using time (0-60 vs 60-120 min) and treatment (Dex vs no Dex) as the two factors. Based on the investigators' previous studies the investigators expect a significant time effect due to Ex-9. If there is an interaction with treatment the investigators would conclude that experimental insulin resistance influences the fasting GLP-1 effect. Data from control subjects will be analyzed identically; here the investigators expect no interaction, indicating that the fasting GLP-1 is a stable measure. In the investigators' previous study using Ex-9 during a glucose clamp, the average coefficient of variation in insulin concentrations at the conclusion of each step in the ramp was 30%. Using this estimate of between subject variation, detecting a 20% difference between subsequent steps in the GLP-1 ramp with a power of 80% and significance level of 0.05 will require 8 subjects.
AIM3: The purpose of Aim-3 of this study is to determine the role of basal GLP-1 action on fasting glucose regulation in lean, obese, pre-diabetic and type 2 diabetic (T2DM) subjects. Approximately 15-20 subjects will complete this cross sectional study of age-matched subjects across the spectrum of glucose tolerance will be used to test the hypothesis that fasting GLP-1 action increases as beta-cell function declines.
Enrolled participants for Aim-3 will be asked to complete two study visits including the consent visit and one infusion visit that will include a hyperglycemic clamp and an infusion of the antagonist Exendin (9-39). The infusion procedure will last approximately 2 hours.
The primary outcome measure for Aim-3 will be the fasting GLP-1 effect. This will be defined as the difference in steady state glucose-stimulated insulin secretion with and without Ex-9. The difference will be expressed as a percentage of glucose stimulated insulin secretion without Ex-9, and serve as the primary variable for comparison among the lean, obese and diabetic cohorts.
- Conditions
- Insulin Secretion
- Being tested
- Exendin (9-39), Dexamethasone, Hyperglycemic Clamp
- Keywords
- Incretins, GLP-1, Exendin-9, Insulin Resistance, Diabetes, Pre-diabetes
- Medical subject headings
- Insulin Resistance, Diabetes Mellitus, Glucose Intolerance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Exendin (9-39)Drug
Also called GLP-1 receptor antagonist
Upon establishing a hyperglycemic clamp (target blood glucose at basal +3 mM) Exendin (9-39) will be infused.
DexamethasoneDrug
Between Visit-2 and Visit-3, Dexamethasone (4 mg tablet) once daily for 5-7 days.
Hyperglycemic ClampOther
A variable infusion of 20% dextrose will begin to clamp the blood glucose at basal +3 mM.
| Study group | Role | What they receive |
|---|---|---|
| Hyperglycemic clamp + Exendin (9-39) | Experimental | During the 2-hour procedure, a variable infusion of 20% dextrose and blood glucose will be clamped at basal + 3mM. Participants will receive an infusion of the GLP-1 receptor antagonist Exendin (9-39) between the 60-120 minute time-points of the clamp. The amount of Ex-9 infused will be 750 pmol/kg/min for 60 minutes. Receives: Drug: Exendin (9-39); Other: Hyperglycemic Clamp |
| Dexamethasone | Experimental | Subjects will be asked to take 4 mg once daily between Visit-2 and Visit-3. Receives: Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
AIM2: C-peptide Levels.
Primary variable for analysis will be C-peptide during the clamp. Mean values will be compared between the control and dexamethasone studies for C-peptide levels during the hyperglycemia plus exendin-(9-39) period of the clamps. For each subject the mean C-peptide during the 60-90 minute period of the initial study (with no dexamethasone) will be compared to the 60-120 period with dexamethasone.
Measured: Minute infusion periods (0-60 vs 60-120) baseline and treatment (Dex vs no Dex)
AIM3: To Determine the Fasting GLP-1 Effect.
The fasting GLP-1 effect will be defined as the difference in steady state glucose stimulated insulin secretion with and without Ex-9.
Measured: Minute infusion periods (0-60 vs 60-120)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2016 (estimated)
- Study start1 Jul 2018
- Primary completion31 Dec 2021
- Study completion31 Dec 2021
Why it stopped: Funding expired
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 Insulin SecretionStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe 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 4
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Collaborators
- Durham VA Medical Center
- Responsible party
- Sponsor
- Investigators
- David D'Alessio, MD, Principal investigator, Durham VA Medical Center, Durham, NC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02844907
- Sponsor's protocol ID
- ENDA-006-15S
- Other IDs
- Pro00070325, 01992
- Status last verified
- Nov 2024
- First submitted
- 22 Jul 2016
- Last updated
- 12 Dec 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- 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 12 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Regulation of Insulin Secretion by the GLP-1 Receptor
- ClinicalTrials.gov ID
- NCT02844907
- Acronym / sponsor ID
- ENDA-006-15S
- Conditions
- Insulin Secretion
- Keywords
- Incretins, GLP-1, Exendin-9, Insulin Resistance, Diabetes, Pre-diabetes
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Funding expired
- Enrolment
- 6 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Collaborators
- Durham VA Medical Center
- Study start
- 1 Jul 2018 (actual)
- Primary completion
- 31 Dec 2021 (actual)
- Study completion
- 31 Dec 2021 (actual)
- First posted
- 26 Jul 2016 (estimated)
- Results
- Posted 12 Dec 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
AIM2: The purpose of Aim-2 of this study is to determine the role of basal GLP-1 action on the beta-cell response to insulin resistance. Healthy subjects will have fasting GLP-1 action determined with GLP-1r blockade before and after induction of experimental insulin resistance. The investigators hypothesize that fasting GLP-1 action will increase to compensate for experimental insulin resistance.
AIM3: The purpose of Aim-3 of this study is to determine the role of basal GLP-1 action on fasting glucose regulation in lean, obese, pre-diabetic and type 2 diabetic (T2DM) subjects. A cross sectional study of age-matched subjects across the spectrum of glucose tolerance will be used to test the hypothesis that fasting GLP-1 action increases as beta-cell function declines.
Detailed description
AIM2: The purpose of this study is to determine the role of basal GLP-1 action on the beta-cell response to insulin resistance. Healthy subjects will have fasting GLP-1 action determined with GLP-1r blockade before and after induction of experimental insulin resistance. The investigators hypothesize that fasting GLP-1 action will increase to compensate for experimental insulin resistance.
The study will enroll up to 20-25 healthy participants and while it is anticipated that the screening blood draw will yield a number of screen failures, it is estimated that 10-15 subjects will complete the entire study protocol. Enrolled participants will be asked to complete three study visits including the consent visit and two infusion study visits that will include hyperglycemic clamp procedures with the addition of the GLP-1 receptor antagonist Exendin (9-39) to determine the fasting GLP-1 effect. Each infusion procedure will last 2 hours. Subjects will be asked to take dexamethasone daily for approximately one week between Visit-2 and Visit-3 to induce insulin resistance.
The investigators will enroll 6-10 additional subjects as controls for effects of time and repeat testing. These individuals will have identical clamps with no dexamethasone at approximately 1 week intervals and will be determined at random by study staff.
The primary outcome for visits 2-3 will be to measure the effects of Ex-9 on fasting glucose-stimulated insulin secretion before and after experimentally induced insulin resistance. The primary experimental variable for analysis will be C-peptide during the clamp. Mean values will be compared between the period of glucose only stimulation and glucose with Ex-9. For each subject in the active treatment arm data will be analyzed using 2-way ANOVA for repeated measures using time (0-60 vs 60-120 min) and treatment (Dex vs no Dex) as the two factors. Based on the investigators' previous studies the investigators expect a significant time effect due to Ex-9. If there is an interaction with treatment the investigators would conclude that experimental insulin resistance influences the fasting GLP-1 effect. Data from control subjects will be analyzed identically; here the investigators expect no interaction, indicating that the fasting GLP-1 is a stable measure. In the investigators' previous study using Ex-9 during a glucose clamp, the average coefficient of variation in insulin concentrations at the conclusion of each step in the ramp was 30%. Using this estimate of between subject variation, detecting a 20% difference between subsequent steps in the GLP-1 ramp with a power of 80% and significance level of 0.05 will require 8 subjects.
AIM3: The purpose of Aim-3 of this study is to determine the role of basal GLP-1 action on fasting glucose regulation in lean, obese, pre-diabetic and type 2 diabetic (T2DM) subjects. Approximately 15-20 subjects will complete this cross sectional study of age-matched subjects across the spectrum of glucose tolerance will be used to test the hypothesis that fasting GLP-1 action increases as beta-cell function declines.
Enrolled participants for Aim-3 will be asked to complete two study visits including the consent visit and one infusion visit that will include a hyperglycemic clamp and an infusion of the antagonist Exendin (9-39). The infusion procedure will last approximately 2 hours.
The primary outcome measure for Aim-3 will be the fasting GLP-1 effect. This will be defined as the difference in steady state glucose-stimulated insulin secretion with and without Ex-9. The difference will be expressed as a percentage of glucose stimulated insulin secretion without Ex-9, and serve as the primary variable for comparison among the lean, obese and diabetic cohorts.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hyperglycemic clamp + Exendin (9-39) | Experimental | Drug: Exendin (9-39), Other: Hyperglycemic ClampDuring the 2-hour procedure, a variable infusion of 20% dextrose and blood glucose will be clamped at basal + 3mM. Participants will receive an infusion of the GLP-1 receptor antagonist Exendin (9-39) between the 60-120 minute time-points of the clamp. The amount of Ex-9 infused will be 750 pmol/kg/min for 60 minutes. |
| Dexamethasone | Experimental | Drug: DexamethasoneSubjects will be asked to take 4 mg once daily between Visit-2 and Visit-3. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- AIM2: SELECTION OF HEALTHY SUBJECTS
- Healthy adults age 20-45 years
- Body Mass Index (BMI) less than or equal to 35.0 kg/m2
- HbA1c less than or equal to 5.7% as measured at screening visit
- Ability to speak and understand English
Key exclusion criteria (29 listed)
- Uncontrolled high blood pressure
- Diabetes or use of diabetes medications such as insulin or metformin
- Evidence of active heart disease, unstable angina or heart failure
- Lung disease or COPD
- Malabsorptive GI disease, such as celiac disease, or gastric bypass
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 (9-39)Also: GLP-1 receptor antagonistUpon establishing a hyperglycemic clamp (target blood glucose at basal +3 mM) Exendin (9-39) will be infused. | Drug | Hyperglycemic clamp + Exendin (9-39) |
| DexamethasoneBetween Visit-2 and Visit-3, Dexamethasone (4 mg tablet) once daily for 5-7 days. | Drug | Dexamethasone |
| Hyperglycemic ClampA variable infusion of 20% dextrose will begin to clamp the blood glucose at basal +3 mM. | Other | Hyperglycemic clamp + Exendin (9-39) |
Primary outcome
AIM2: C-peptide Levels.
Time frame: Minute infusion periods (0-60 vs 60-120) baseline and treatment (Dex vs no Dex)
Primary variable for analysis will be C-peptide during the clamp. Mean values will be compared between the control and dexamethasone studies for C-peptide levels during the hyperglycemia plus exendin-(9-39) period of the clamps. For each subject the mean C-peptide during the 60-90 minute period of the initial study (with no dexamethasone) will be compared to the 60-120 period with dexamethasone.
AIM3: To Determine the Fasting GLP-1 Effect.
Time frame: Minute infusion periods (0-60 vs 60-120)
The fasting GLP-1 effect will be defined as the difference in steady state glucose stimulated insulin secretion with and without Ex-9.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Insulin Secretion
Active, not recruitingPhase 2
Frexalimab in Preservation of Endogenous Insulin Secretion Compared to Placebo in Adults and Adolescents on Top of Insulin Therapy (FABULINUS)
Type 1 Diabetes Mellitus
RecruitingPhase 2
Effects of Different Fish Oil Types on Type 2 Diabetes Risk Factors in High-Risk Adults
Type 2 Diabetes, Prediabetes (Insulin Resistance, Impaired Glucose Tolerance)
Active, not recruitingPhase 2
Effect of Probiotics Versus Metformin on Glycemic Control, Insulin Sensitivity and Insulin Secretion in Prediabetes.
PreDiabetes, Impaired Glucose Tolerance
Recruiting
Insulin and Insulin Pulses During Fasting
PreDiabetes
Active, not recruitingPhase 1
A Study to Evaluate the Effect of Retatrutide on Insulin Secretion and Insulin Sensitivity in Adult Participants With Type 2 Diabetes Mellitus
Diabetes Mellitus, Insulin Sensitivity
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.
David D'Alessio, MD principal investigator
Durham VA Medical Center, Durham, NC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Exendin (9-39), Dexamethasone and Hyperglycemic Clamp in people with Insulin Secretion, run by VA Office of Research and Development 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 16 inclusion and 29 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: stopped early, as of the sponsor's last update on 12 Dec 2024. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 12 Dec 2024). 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?
AIM2: C-peptide Levels. (time frame: Minute infusion periods (0-60 vs 60-120) baseline and treatment (Dex vs no Dex)). The study lists 2 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 12 Dec 2024.