The Methodology Assessment of Glucose Dependent Insulin SecretionPhase 1NCT00782418

A Study to Compare Methodologies for Assessing Glucose-Dependent Insulin Secretion (0000-104)(COMPLETED)

A Phase 1 study testing Comparator: exenatide in people with The Methodology Assessment of Glucose Dependent Insulin Secretion, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This study will compare graded glucose infusion (GGI) to the hyperglycemic clamp (HGC) for assessment of glucose-dependent insulin secretion (GDIS) using exenatide as a probe. Read more about this study

Who is it for?: Ages 18 to 45 years, men onlyHealthy volunteers can take part
Conditions the study is for: The Methodology Assessment of Glucose Dependent Insulin Secretion
What is being tested?: Comparator: exenatide
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 27 participants
Where: No sites listed yet
Study dates: Sep 2008to Mar 2009
Phase: Phase 1
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 45 years
Men only
Healthy volunteers accepted
Adult

Who may be able to join

Subject has a Body Mass Index (BMI) of less than or equal to 26 kg/m2 at screening
Subject is judged to be in good health
Subject has been a nonsmoker for at least 3 months
Subject is willing to avoid strenuous physical activity for the duration of the study

Who cannot join

Subject has a history of high blood pressure requiring treatment
Subject has a history of diabetes or a family history of diabetes mellitus
Subject is unable to discontinue all prescription and non-prescription drugs for duration of study
Subject consumes more than 3 alcoholic beverages per day
Subject consumes more than 6 servings of caffeinated beverages per day (1 serving = 120mg caffeine)
Subject has had major surgery or has donated or loss 1 unit of blood within 4 weeks of screening

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Subject has multiple and/or severe allergies to foods or drugs
Subject is a regular user of illegal drugs
Subject is unwilling or unable to consume the standardized meals during the study and/or is on a carbohydrate restricted diet

About this study

Official title: A Randomized Clinical Trial to Study Glucose Dependent Insulin Secretion Methodologies in Healthy Lean Male Subjects

This study will compare graded glucose infusion (GGI) to the hyperglycemic clamp (HGC) for assessment of glucose-dependent insulin secretion (GDIS) using exenatide as a probe.

Conditions: The Methodology Assessment of Glucose Dependent Insulin Secretion
Being tested: Comparator: exenatide, Comparator: Placebo

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Comparator: exenatideDrug
Also called Byetta
exenatide in two 5mcg subcutaneous doses 120 minutes apart, followed by either HGC or GGI. After a 14 day washout period two additional 5mcg doses will be administered, followed by HCG or GGI.
Comparator: exenatideDrug
Also called Byetta
exenatide in two 1.5mcg subcutaneous doses 120 minutes apart, followed by either HGC or GGI. After a 14 day washout period two additional 1.5mcg doses will be administered, followed by HCG or GGI.
Comparator: PlaceboDrug
5% osmitrol in two 60 mcL subcutaneous doses 120 minutes apart, followed by either HGC or GGI. After a 14 day washout period two additional 60 mcL doses will be administered, followed by HCG or GGI.

Study groups in NCT00782418
Study group	Role	What they receive
1	Active comparator	exenatide 5mcg Receives: Drug: Comparator: exenatide
2	Active comparator	exenatide 1.5mcg Receives: Drug: Comparator: exenatide
3	Placebo comparator	Placebo Receives: Drug: Comparator: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Baseline in Insulin Secretion Rate (ISR) Normalized to Ambient Plasma Glucose
Comparison of Glucose Dependent Insulin Secretion (GDIS) measured after HGC at steady-state to GDIS measured after GGI at the highest glucose infusion rate.
Insulin Secretion Rate (ISR)/ Blood Glucose (BG)
Measured: Steady-state of HGC: 90 - 120 minutes post dose; highest glucose infusion rate of GGI: 120 - 160 minutes post dose
Change From Baseline in C-peptide Concentration
Measured: Pre and Post glucose infusion
Change From Baseline in Insulin Concentration
Measured: Pre and Post glucose infusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2008Mar 2009

First posted31 Oct 2008 (estimated)
Study startSep 2008
Primary completionFeb 2009
Study completionMar 2009

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.
Publications (1)Papers the sponsor has linked to this study.
Other trials for The Methodology Assessment of Glucose Dependent Insulin SecretionStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe 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
Primary purpose: Diagnosis
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 27 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00782418
Sponsor's protocol ID: 0000-104
Other IDs: 2008_568
Status last verified: Nov 2016
First submitted: 29 Oct 2008
Last updated: 21 Dec 2016
Results posted: Yes, on ClinicalTrials.gov

Publications

Shankar SS, Shankar RR, Mixson LA, Miller DL, Chung C, Cilissen C, Beals CR, Stoch SA, Steinberg HO, Kelley DE. Linearity of beta-cell response across the metabolic spectrum and to pharmacology: insights from a graded glucose infusion-based investigation series. Am J Physiol Endocrinol Metab. 2016 Jun 1;310(11):E865-73. doi: 10.1152/ajpendo.00527.2015. Epub 2016 Apr 12.
PubMed 27072496

Study at a glance

From the registry record, last updated by the sponsor on 21 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized Clinical Trial to Study Glucose Dependent Insulin Secretion Methodologies in Healthy Lean Male Subjects
ClinicalTrials.gov ID: NCT00782418
Acronym / sponsor ID: 0000-104
Conditions: The Methodology Assessment of Glucose Dependent Insulin Secretion
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 27 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: Sep 2008
Primary completion: Feb 2009 (actual)
Study completion: Mar 2009 (actual)
First posted: 31 Oct 2008 (estimated)
Results: Posted 6 Apr 2010

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This study will compare graded glucose infusion (GGI) to the hyperglycemic clamp (HGC) for assessment of glucose-dependent insulin secretion (GDIS) using exenatide as a probe.

Study design

Primary purpose: Diagnosis
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 3

Arm	Type	Receives
1	Active comparator	Drug: Comparator: exenatideexenatide 5mcg
2	Active comparator	Drug: Comparator: exenatideexenatide 1.5mcg
3	Placebo comparator	Drug: Comparator: PlaceboPlacebo

Who may qualify

Ages: 18 to 45 years
Sex: Male only
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (4 listed)

Subject has a Body Mass Index (BMI) of less than or equal to 26 kg/m2 at screening
Subject is judged to be in good health
Subject has been a nonsmoker for at least 3 months
Subject is willing to avoid strenuous physical activity for the duration of the study

Key exclusion criteria (9 listed)

Subject has a history of high blood pressure requiring treatment
Subject has a history of diabetes or a family history of diabetes mellitus
Subject is unable to discontinue all prescription and non-prescription drugs for duration of study
Subject consumes more than 3 alcoholic beverages per day
Subject consumes more than 6 servings of caffeinated beverages per day (1 serving = 120mg caffeine)

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
Comparator: exenatideAlso: Byettaexenatide in two 5mcg subcutaneous doses 120 minutes apart, followed by either HGC or GGI. After a 14 day washout period two additional 5mcg doses will be administered, followed by HCG or GGI.	Drug	1
Comparator: exenatideAlso: Byettaexenatide in two 1.5mcg subcutaneous doses 120 minutes apart, followed by either HGC or GGI. After a 14 day washout period two additional 1.5mcg doses will be administered, followed by HCG or GGI.	Drug	2
Comparator: Placebo5% osmitrol in two 60 mcL subcutaneous doses 120 minutes apart, followed by either HGC or GGI. After a 14 day washout period two additional 60 mcL doses will be administered, followed by HCG or GGI.	Drug	3

Primary outcome

Change From Baseline in Insulin Secretion Rate (ISR) Normalized to Ambient Plasma Glucose
Time frame: Steady-state of HGC: 90 - 120 minutes post dose; highest glucose infusion rate of GGI: 120 - 160 minutes post dose
Comparison of Glucose Dependent Insulin Secretion (GDIS) measured after HGC at steady-state to GDIS measured after GGI at the highest glucose infusion rate. Insulin Secretion Rate (ISR)/ Blood Glucose (BG)
Change From Baseline in C-peptide Concentration
Time frame: Pre and Post glucose infusion
Change From Baseline in Insulin Concentration
Time frame: Pre and Post glucose infusion

Results and safety

Results posted to the registry on 6 Apr 2010, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
HGC - Exenatide 5 μg	3	1
HGC - Exenatide 1.5 μg	4	4
HGC - Placebo	4	4
Exenatide 5 ug Down Dosed to Placebo (HGC)	2	2
GGI - Exenatide 5 μg	5	4
GGI - Exenatide 1.5 μg	5	4
Placebo (HGC or GGI)	4	4

Primary outcome: Change From Baseline in Insulin Secretion Rate (ISR) Normalized to Ambient Plasma Glucose

Time frame: Steady-state of HGC: 90 - 120 minutes post dose; highest glucose infusion rate of GGI: 120 - 160 minutes post dose. Geometric mean (Full Range). Unit: (ng/min) / (mg/dL)

Measure	HGC - Exenatide 5 μg n = 6	HGC - Exenatide 1.5 μg n = 8	HGC - Placebo n = 11	GGI - Exenatide 5 μg n = 6	GGI - Exenatide 1.5 μg n = 9	GGI - Placebo n = 8
Value	2.14 (1.52 to 2.52)	1.49 (0.78 to 2.16)	0.53 (0.19 to 0.73)	2.95 (0.94 to 3.88)	2.07 (0.82 to 3.30)	0.71 (0.10 to 1.22)

HGC - Exenatide 5 μg vs HGC - Placebo: Least Squares Mean: 1.60 (90% CI 1.29 to 1.92), p <0.001, ANOVA
HGC - Exenatide 1.5 μg vs HGC - Placebo: Least Squares Mean: 0.95 (90% CI 0.66 to 1.24), p <0.001, ANOVA
GGI - Exenatide 5 μg vs GGI - Placebo: Least Squares Mean: 2.32 (90% CI 1.57 to 3.06), p <0.001, ANOVA

Population analysed: All subjects treated

Primary outcome: Change From Baseline in C-peptide Concentration

Time frame: Pre and Post glucose infusion. Least squares mean (Full Range). Unit: ng/mL

Measure	HGC - Exenatide 5 μg n = 6	HGC - Exenatide 1.5 μg n = 8	HGC - Placebo n = 11
Value	29.3 (25.2 to 35.1)	22.6 (14.0 to 34.1)	6.24 (2.3 to 8.9)

HGC - Exenatide 5 μg vs HGC - Placebo: Least Squares Mean: 23.1 (90% CI 19.2 to 27.0), p <0.001, ANOVA
HGC - Exenatide 1.5 μg vs HGC - Placebo: Least Squares Mean: 16.4 (90% CI 12.6 to 20.1), p <0.001, ANOVA

Population analysed: All subjects treated

Primary outcome: Change From Baseline in Insulin Concentration

Time frame: Pre and Post glucose infusion. Least squares mean (Full Range). Unit: μIU(insulin)/mL

Measure	HGC - Exenatide 5 μg n = 6	HGC - Exenatide 1.5 μg n = 8	HGC - Placebo n = 11
Value	592 (445 to 695)	293 (128 to 597)	46.5 (16.2 to 123)

HGC - Exenatide 5 μg vs HGC - Placebo: Least Squares Mean: 545.0 (90% CI 451.4 to 638.7), p <0.001, ANOVA
HGC - Exenatide 1.5 μg vs HGC - Placebo: Least Squares Mean: 246.6 (90% CI 160.9 to 323.3), p <0.001, ANOVA

Population analysed: All subjects treated

Adverse events

Time frame: Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
HGC - Exenatide 5 μg	0 of 9 (0%)	4 of 9 (44.4%)	Not reported
HGC - Exenatide 1.5 μg	0 of 9 (0%)	4 of 9 (44.4%)	Not reported
HGC - Placebo	0 of 10 (0%)	4 of 10 (40%)	Not reported
GGI - Exenatide 5 μg	1 of 7 (14.3%)	6 of 7 (85.7%)	Not reported
GGI - Exenatide 1.5 μg	0 of 8 (0%)	3 of 8 (37.5%)	Not reported
GGI - Placebo	0 of 11 (0%)	2 of 11 (18.2%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Dec 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 27072496Shankar SS, Shankar RR, Mixson LA, Miller DL, Chung C, Cilissen C, Beals CR, Stoch SA, Steinberg HO, Kelley DE. Linearity of beta-cell response across the metabolic spectrum and to pharmacology: insights from a graded glucose infusion-based investigation series. Am J Physiol Endocrinol Metab. 2016 Jun 1;310(11):E865-73. doi: 10.1152/ajpendo.00527.2015. Epub 2016 Apr 12.

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.

Medical Monitor study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Comparator: exenatide in people with The Methodology Assessment of Glucose Dependent Insulin Secretion, run by Merck Sharp & Dohme LLC.

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 4 inclusion and 9 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 21 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.

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?

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.

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 6 Apr 2010). 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?

Change From Baseline in Insulin Secretion Rate (ISR) Normalized to Ambient Plasma Glucose (time frame: Steady-state of HGC: 90 - 120 minutes post dose; highest glucose infusion rate of GGI: 120 - 160 minutes post dose). 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?

On the ClinicalTrials.gov record for NCT00782418, 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 21 Dec 2016; AzTrials last refreshed its copy on 28 Oct 2026.