Type 2 Diabetes MellitusPhase 2/3NCT01607450
Modulation of Human Myocardial Metabolism by GLP-1 Dose Response
A Phase 2/3 study testing GLP-1 Low Dose, GLP-1 Mid-Range Dose and GLP-1 High Dose in people with Type 2 Diabetes Mellitus and Healthy, run by Indiana University at 1 site in United States.
Trial summary
The objective of this proposal is to provide quantitative dose-response data for effects of GLP-1 on myocardial glucose uptake in healthy control subjects and obese type 2 diabetic subjects, in support of the design of later studies evaluating therapeutic applications of GLP-1 to heart disease. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Type 2 Diabetes Mellitus, Healthy
- What is being tested?
- GLP-1 Low Dose, GLP-1 Mid-Range Dose and GLP-1 High Dose
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteUnited States
- Study dates
- May 2010to Dec 2012
- Phase
- Phase 2/3
- 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 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Age 18-60
- Lean subjects will be defined as having a BMI <25 kg/m2, in good general health, taking no regular medications
- Diabetic subjects will be obese (BMI >30 kg/m2 but <40 kg/m2), HbA1c 7.0-10.0%, treated with diet and exercise plus oral agents or injected insulin. All diabetic subjects will be treated with injected insulin for 2 weeks prior to study, to avoid potential confounding effects of other antidiabetic agents.
Who cannot join
- Chronic illnesses or infections (other than type 2 diabetes)
- Known coronary artery disease or abnormal ECG on screening evaluation
- Blood pressure > 160/100 mmHg on two occasions during screening evaluations. Current use of 3 or fewer blood pressure medications with blood pressure below this cutpoint will be acceptable.
- Total cholesterol > 240 mg/dL. Current use of 2 or fewer lipid lowering agents with cholesterol below this cutpoint will be acceptable.
- Diabetic subjects: Treatment with a GLP-1 agonist or DPP4 inhibitor within the past 6 months
- Known intolerance to injected GLP-1 agonist
Show all 13Show fewer
- Treatment with PPAR gamma agonists currently or within the past 6 months
- Recognized microvascular complications (retinopathy, nephropathy, neuropathy)
- Unwillingness or inability to use injected insulin for the purposes of this study
- Chronic pain or other physical conditions which limit ability to remain supine for the duration of the study protocol
- History of claustrophobia, musculoskeletal or other factors which would result in an inability to comfortably remain within PET scanner gantry for the duration of the imaging protocol
- Occupational, investigational or other known radiation exposure which, together with the planned radiologic studies, will result in greater than 500 mrem total exposure in a contiguous 12 month period
- For female participants, current pregnancy
Trial locations and contacts
1 site in 1 country.
United States1 site
Indiana Clinical Research Center
Indianapolis, Indiana, 46202
About this study
The objective of this proposal is to provide quantitative dose-response data for effects of GLP-1 on myocardial glucose uptake in healthy control subjects and obese type 2 diabetic subjects, in support of the design of later studies evaluating therapeutic applications of GLP-1 to heart disease.
Aim 1: To measure the effects of GLP-1 infusion on myocardial fuel selection in lean healthy humans under fasting (fatty acid-dominant) conditions. Four groups of 10 lean healthy subjects will be studied during infusions of 0 (saline control), 0.5, 1.5, and 4.0 pmol/kg/min GLP-1 (one study per subject). Cardiac metabolism will be measured using PET, using a dual-tracer approach which allows measurement of myocardial glucose uptake (the primary endpoint) along with total oxidation rate and myocardial perfusion (secondary endpoints). In concert with measures of circulating metabolites and regulatory hormones, the investigators will produce the most comprehensive assessment of actions of GLP-1 on myocardial metabolism in humans to date. Effects of each dose will be compared to the saline control, plus the investigators will combine all data and use nonlinear curve-fitting to derive sensitivity (ED50) and maximal responses for GLP-1 effects on myocardial glucose uptake.
Read more
Aim 2: To measure the effects of GLP-1 infusion on myocardial fuel selection in obese type 2 diabetic humans under fasting (fatty acid-dominant) conditions Four groups of 10 obese type 2 diabetic subjects will be studied during infusions of 0, 0.5, 1.5, and 4.0 pmol/kg/min GLP-1 as under Aim 1. Analyses will be parallel to those described under Aim 1. Results from Aims 1 and 2 will be combined to allow direct comparison of the dose-response between nondiabetic control and type 2 diabetic subjects.
No literature has been published to inform dose selection in the design of clinical trials of GLP-1 for modulation of heart fuel selection. With our expertise and experience in PET measurement of heart metabolism in diabetes, the investigators are uniquely positioned to fill this gap in knowledge. These studies are a necessary preamble to further evaluation of the potential for GLP-1 based treatments in heart disease.
- Conditions
- Type 2 Diabetes Mellitus, Healthy
- Being tested
- GLP-1 Low Dose, GLP-1 Mid-Range Dose, GLP-1 High Dose, Saline
- Keywords
- Type 2 diabetes mellitus, lean healthy control
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GLP-1 Low DoseDrug
0.5mmol/kg/hr GLP-1 for 12 hours prior to PET study
GLP-1 Mid-Range DoseDrug
1.5mmol/kg/min for 12 hours prior to PET study
GLP-1 High DoseDrug
4.0mmol/kg/min GLP-1 for 12 hours prior to PET study
SalineDrug
Also called Normal Saline
Normal saline placebo infusion for 12 hours prior to PET study
| Study group | Role | What they receive |
|---|---|---|
| Saline | Other | 12 hour saline (control) infusion prior to PET study Receives: Drug: Saline |
| GLP-1 Low dose | Experimental | GLP-1 Low Dose: 0.5 pmol/kg/min for 12 hours prior to PET study Receives: Drug: GLP-1 Low Dose |
| GLP-1 Mid-Range Dose | Experimental | GLP-1 Mid-Range Dose: 1.5 pmol/kg/min for 12 hours prior to PET study Receives: Drug: GLP-1 Mid-Range Dose |
| GLP-1 High Dose | Experimental | GLP-1 High Dose: 4.0 pmol/kg/min for 12 hours prior to PET study Receives: Drug: GLP-1 High Dose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Myocardial Glucose Uptake.
Myocardial glucose uptake measured using 18FDG PET, quantified using a 3-compartment model with a lumped constant of 1.0.
Measured: After 12 hours of glucagon-like peptide 1 (GLP-1) exposure
Secondary outcomes (4)
Myocardial Blood Flow
Myocardial perfusion derived from acetate kinetics
Measured: After 12 hours of GLP-1 exposure
Myocardial Total Oxidation Rate
MVO2 derived from acetate kinetics
Measured: After 12 hours of GLP-1 exposure
Cardiac Index
Impedance cardiography-derived measurement of cardiac index, assessed following 12 hour exposure to treatment condition concurrent with the PET measurements.
Measured: After 12 hours of GLP-1 exposure
GLP-1 Concentrations
Achieved GLP-1 concentrations at the end of the 12 hour treatment exposure
Measured: After 12 hours of GLP-1 exposure
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2012 (estimated)
- Study startMay 2010
- Primary completionDec 2012
- Study completionDec 2012
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 Type 2 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by Indiana 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 2/3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Indiana University
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor
- Investigators
- Kieren J Mather, MD, Principal investigator, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01607450
- Sponsor's protocol ID
- 1010002497
- Other IDs
- R21HL092799
- Status last verified
- Jan 2016
- First submitted
- 21 May 2012
- Last updated
- 17 Feb 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Modulation of Human Myocardial Metabolism by GLP-1 Dose Response
- ClinicalTrials.gov ID
- NCT01607450
- Acronym / sponsor ID
- 1010002497
- Conditions
- Type 2 Diabetes Mellitus, Healthy
- Keywords
- Type 2 diabetes mellitus, lean healthy control
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Indiana UniversityUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- May 2010
- Primary completion
- Dec 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 30 May 2012 (estimated)
- Results
- Posted 17 Feb 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objective of this proposal is to provide quantitative dose-response data for effects of GLP-1 on myocardial glucose uptake in healthy control subjects and obese type 2 diabetic subjects, in support of the design of later studies evaluating therapeutic applications of GLP-1 to heart disease.
Aim 1: To measure the effects of GLP-1 infusion on myocardial fuel selection in lean healthy humans under fasting (fatty acid-dominant) conditions. Four groups of 10 lean healthy subjects will be studied during infusions of 0 (saline control), 0.5, 1.5, and 4.0 pmol/kg/min GLP-1 (one study per subject). Cardiac metabolism will be measured using PET, using a dual-tracer approach which allows measurement of myocardial glucose uptake (the primary endpoint) along with total oxidation rate and myocardial perfusion (secondary endpoints). In concert with measures of circulating metabolites and regulatory hormones, the investigators will produce the most comprehensive assessment of actions of GLP-1 on myocardial metabolism in humans to date. Effects of each dose will be compared to the saline control, plus the investigators will combine all data and use nonlinear curve-fitting to derive sensitivity (ED50) and maximal responses for GLP-1 effects on myocardial glucose uptake.
Aim 2: To measure the effects of GLP-1 infusion on myocardial fuel selection in obese type 2 diabetic humans under fasting (fatty acid-dominant) conditions Four groups of 10 obese type 2 diabetic subjects will be studied during infusions of 0, 0.5, 1.5, and 4.0 pmol/kg/min GLP-1 as under Aim 1. Analyses will be parallel to those described under Aim 1. Results from Aims 1 and 2 will be combined to allow direct comparison of the dose-response between nondiabetic control and type 2 diabetic subjects.
No literature has been published to inform dose selection in the design of clinical trials of GLP-1 for modulation of heart fuel selection. With our expertise and experience in PET measurement of heart metabolism in diabetes, the investigators are uniquely positioned to fill this gap in knowledge. These studies are a necessary preamble to further evaluation of the potential for GLP-1 based treatments in heart disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Saline | Other | Drug: Saline12 hour saline (control) infusion prior to PET study |
| GLP-1 Low dose | Experimental | Drug: GLP-1 Low DoseGLP-1 Low Dose: 0.5 pmol/kg/min for 12 hours prior to PET study |
| GLP-1 Mid-Range Dose | Experimental | Drug: GLP-1 Mid-Range DoseGLP-1 Mid-Range Dose: 1.5 pmol/kg/min for 12 hours prior to PET study |
| GLP-1 High Dose | Experimental | Drug: GLP-1 High DoseGLP-1 High Dose: 4.0 pmol/kg/min for 12 hours prior to PET study |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Age 18-60
- Lean subjects will be defined as having a BMI <25 kg/m2, in good general health, taking no regular medications
- Diabetic subjects will be obese (BMI >30 kg/m2 but <40 kg/m2), HbA1c 7.0-10.0%, treated with diet and exercise plus oral agents or injected insulin. All diabetic subjects will be treated with injected insulin for 2 weeks prior to study, to avoid potential confounding effects of other antidiabetic agents.
Key exclusion criteria (13 listed)
- Chronic illnesses or infections (other than type 2 diabetes)
- Known coronary artery disease or abnormal ECG on screening evaluation
- Blood pressure > 160/100 mmHg on two occasions during screening evaluations. Current use of 3 or fewer blood pressure medications with blood pressure below this cutpoint will be acceptable.
- Total cholesterol > 240 mg/dL. Current use of 2 or fewer lipid lowering agents with cholesterol below this cutpoint will be acceptable.
- Diabetic subjects: Treatment with a GLP-1 agonist or DPP4 inhibitor within the past 6 months
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 |
|---|---|---|
| GLP-1 Low Dose0.5mmol/kg/hr GLP-1 for 12 hours prior to PET study | Drug | GLP-1 Low dose |
| GLP-1 Mid-Range Dose1.5mmol/kg/min for 12 hours prior to PET study | Drug | GLP-1 Mid-Range Dose |
| GLP-1 High Dose4.0mmol/kg/min GLP-1 for 12 hours prior to PET study | Drug | GLP-1 High Dose |
| SalineAlso: Normal SalineNormal saline placebo infusion for 12 hours prior to PET study | Drug | Saline |
Primary outcome
Myocardial Glucose Uptake.
Time frame: After 12 hours of glucagon-like peptide 1 (GLP-1) exposure
Myocardial glucose uptake measured using 18FDG PET, quantified using a 3-compartment model with a lumped constant of 1.0.
4 secondary outcomes
Myocardial Blood Flow
Time frame: After 12 hours of GLP-1 exposure
Myocardial Total Oxidation Rate
Time frame: After 12 hours of GLP-1 exposure
Cardiac Index
Time frame: After 12 hours of GLP-1 exposure
GLP-1 Concentrations
Time frame: After 12 hours of GLP-1 exposure
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Kieren J Mather, MD principal investigator
Indiana University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing GLP-1 Low Dose, GLP-1 Mid-Range Dose and GLP-1 High Dose in people with Type 2 Diabetes Mellitus and Healthy, run by Indiana 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 13 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 17 Feb 2016. 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 17 Feb 2016). 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?
Myocardial Glucose Uptake. (time frame: After 12 hours of glucagon-like peptide 1 (GLP-1) exposure). 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 17 Feb 2016.