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Type 2 DiabetesPhase 4COCONUTNCT04307797

Effect of Glucagon and Glucagon-like Peptide-1 Co-agonism on Cardiac Function and Metabolism in Overweight Participants with Type 2 Diabetes

A Phase 4 study testing 0.9% Sodium-chloride, Exenatide (50ng/min for 30 minutes loading followed by 25ng/min maintenance) and glucagon 12.5ng/kg/min and Glucagon 12.5ng/kg/min and 0.9% saline in people with Type 2 Diabetes and Obesity, run by Cambridge University Hospitals NHS Foundation Trust at 1 site in United Kingdom.

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

The study seeks to explore the cardiovascular effects of co-agonism at the glucagon and (glucagon-like peptide-1) GLP-1 receptor. Glucagon and exenatide will be intravenously infused into participants with type 2 diabetes (T2DM). Read more about this study

Who is it for?
Ages 18 to 99 years
Conditions the study is for
Type 2 Diabetes, Obesity
What is being tested?
0.9% Sodium-chloride, Exenatide (50ng/min for 30 minutes loading followed by 25ng/min maintenance) and glucagon 12.5ng/kg/min and Glucagon 12.5ng/kg/min and 0.9% saline
Type of treatment
Injection or infusion
How many people
10 participants
Where
1 siteUnited Kingdom
Study dates
18 Jan 2022to 7 Oct 2022
Phase
Phase 4
Are there results?
None posted in the registry

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 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Written informed consent to participate
  • Aged >18 years
  • Clinical diagnosis of T2DM, either diet controlled or treated with metformin (to be withheld on the morning of the imaging visit)
  • BMI ≥25kg/m2
  • Current non-smoker

Who cannot join

  • Females of childbearing potential (Part A only) / current pregnancy (all parts)
  • Sustained Hypertension (sustained BP >160/100mmHg) or hypotension (systolic BP below 90 mmHg)
  • Clinically significant heart disease
  • Implanted heart pacemaker or implantable cardioverter defibrillator (ICD)
  • Known active malignancy other than skin cancer
  • Known renal failure (creatinine >150µmol/L)
Show all 13Show fewer
  • Known type one diabetes mellitus / known or clinically suspected diagnosis of a monogenic form of diabetes
  • Poorly controlled blood glucose
  • Current daily use of anti-diabetic medication including Insulin, GLP-1 based agonists, DPP4i or any other medication known to interact with either of the study drugs (exenatide or glucagon)
  • Current involvement in the active treatment phase of other research studies, (excluding observational/non-interventional).
  • Contraindication for MRI/PET scan, i.e. any reason which precludes MRI imaging according to local policy (ie internal pacemaker/defibrillator, metal fragments, claustrophobia)
  • Participation in research studies in the last 3 years involving radiation (if the effective dose exceeded 10mSv). This does not include any diagnostic or therapeutic exposures which were clinically justified.
  • Any other clinical reason which may preclude entry in the opinion of the investigator

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

  • Cambridge University Hospitals NHS Foundation Trust and The University of Cambridge

    Cambridge, Cambridgeshire, CB2 0QQ

Other trials in United Kingdom

About this study

Official title: A Pilot Study on the Effect of Glucagon and Glucagon-like Peptide-1 Co-agonism on Cardiac Function and Metabolism in Overweight Participants with Type 2 Diabetes (COCONUT)

The study seeks to explore the cardiovascular effects of co-agonism at the glucagon and (glucagon-like peptide-1) GLP-1 receptor. Glucagon and exenatide will be intravenously infused into participants with type 2 diabetes (T2DM). Overall, the aim of the study is to further the investigator's understanding on the role these endogenous substances have on normal cardiac physiology, myocardial energetics and myocardial glucose uptake through a series of PET and MRI imaging studies

Read the detailed description

This is a single-centre, single-blinded pilot study designed to understand the role the GLP-1 receptor agonist, exenatide, and glucagon receptor co-agonism has on normal cardiac physiology, myocardial energetics and myocardial glucose utilisation.

Part A - Overweight participants with type 2 diabetes will act as their own control and will undergo a series of three imaging studies (in a randomised order) as detailed below:

  1. Cardiac positron emission tomography-magnetic resonance imaging (PET-MRI) with fluorine-18-fluorodeoxyglucose (18F-FDG) with placebo (0.9% saline) infusion
  2. Cardiac PET-MRI with 18F-FDG with co-infusion of exenatide and glucagon
  3. Cardiac PET-MRI with 18F-FDG with infusion of glucagon

Part B - Overweight participants with type 2 diabetes will act as their own control and will undergo a series of two imaging studies (in a randomised order), followed by one optional visit as detailed below:

  1. 7T Phosphorus (P) 31 magnetic resonance spectroscopy (MRS) (31P-MRS) with placebo (0.9% saline) infusion
  2. 7T 31P-MRS with co-infusion of glucagon and exenatide 3 (optional) 7T 31P-MRS with infusion of glucagon

Study outcome measures are detailed below

Being tested
0.9% Sodium-chloride, Exenatide (50ng/min for 30 minutes loading followed by 25ng/min maintenance) and glucagon 12.5ng/kg/min, Glucagon 12.5ng/kg/min and 0.9% saline, Glucagon 12.5ng/kg/min
Medical subject headings
Diabetes Mellitus, Type 2, Obesity

What participants receive

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

  • 0.9% Sodium-chlorideDrug

    Part A - 0.9% saline infusion during cardiac PET-MRI scan

  • Exenatide (50ng/min for 30 minutes loading followed by 25ng/min maintenance) and glucagon 12.5ng/kg/minDrug

    Also called Byetta

    Part A - exenatide and glucagon infusion during cardiac PET-MRI scan

  • Glucagon 12.5ng/kg/min and 0.9% salineDrug

    Part A - Glucagon and 0.9% saline infusion during PET-MRI scan

  • 0.9% Sodium-chlorideDrug

    Part B - 0.9% saline infusion during 7T 31P MRS scan

  • Exenatide (50ng/min for 30 minutes loading followed by 25ng/min maintenance) and glucagon 12.5ng/kg/minDrug

    Part B - exenatide and glucagon infusion during 7T 31P MRS scan

  • Glucagon 12.5ng/kg/minDrug

    Part B - Glucagon infusion during 7T 31P MRS scan

What is being measured

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

  1. Part A - Myocardial glucose uptake

    Difference in myocardial glucose uptake between 0.9% saline, glucagon:exenatide and glucagon scan as measured by 18F-FDG

    Measured: Comparison between scans over a maximum period of 16 weeks

  2. Part A - Global longitudinal strain / global circumferential strain / global radial strain

    Difference in global longitudinal strain / global circumferential strain / global radial strain between 0.9% saline, glucagon:exenatide and glucagon scan as measured by CMR

    Measured: Comparison between scans over a maximum period of 16 weeks

  3. Part A - Ejection fraction

    Difference in ejection fraction between 0.9% saline, glucagon:exenatide and glucagon scan as measured by CMR

    Measured: Comparison between scans over a maximum period of 16 weeks

  4. Part A - Stroke volume

    Difference in stroke volume between 0.9% saline, glucagon:exenatide and glucagon scan as measured by CMR

    Measured: Comparison between scans over a maximum period of 16 weeks

  5. Part A - Cardiac output

    Difference in cardiac output between 0.9% saline, glucagon:exenatide and glucagon scan as measured by CMR

    Measured: Comparison between scans over a maximum period of 16 weeks

  6. Part B - Changes in phosphocreatine/adenosine (PCr/ATP) radio

    Changes in PCr/ATP radio between 0.9% saline, glucagon:exenatide and glucagon (optional) in the mid-interventricular septum as a measure of cardiac energy status as measured by 7T phosphorus (P) 31 magnetic resonance spectroscopy (MRS)

    Measured: Comparison between scans over a maximum period of 16 weeks

  7. Part B - Changes in absolute concentrations of PCr and ATP defined by AHA 17- segment territory as a measure of cardiac energy status (determined by 31P-MRS)

    Changes in absolute concentrations of PCr and ATP between 0.9% saline, glucagon:exenatide and glucagon (optional) as defined by AHA 17-segment territory as a measure of cardiac energy status (determined by 7T 31P-MRS)

    Measured: Comparison between scans over a maximum period of 16 weeks

Secondary outcomes (14)

  1. Part A - End systolic/diastolic ventricular/atrial volumes

    Difference in end systolic/diastolic ventricular/atrial volumes between 0.9% saline, glucagon:exenatide and glucagon scan as measured by CMR

    Measured: Comparison between scans over a maximum period of 16 weeks

  2. Part A - Radial strain

    Difference in radial strain between 0.9% saline, glucagon:exenatide and glucagon scan as measured by CMR

    Measured: Comparison between scans over a maximum period of 16 weeks

  3. Part A - Global systolic/diastolic longitudinal/circumferential/radial strain rate

    Difference in global systolic/diastolic longitudinal/circumferential/radial strain rate between 0.9% saline, glucagon:exenatide and glucagon scan as measured by CMR

    Measured: Comparison between scans over a maximum period of 16 weeks

  4. Part A - Relationship between early and late filling (from mitral flow)

    Difference in early and late filling (from mitral flow) between 0.9% saline, glucagon:exenatide and glucagon scan as measured by CMR

    Measured: Comparison between scans over a maximum period of 16 weeks

  5. Part A/B - Heart rate

    Difference in heart rate between 0.9% saline, glucagon:exenatide and glucagon

    Measured: Comparison between infusions (placebo vs drug) over a maximum period of 16 weeks

  6. Part A/B - Blood pressure

    Difference in blood pressure between 0.9% saline, glucagon:exenatide and glucagon

    Measured: Comparison between infusions (placebo vs drug) over a maximum period of 16 weeks

  7. Part A/B - Glucose

    Difference in glucose between 0.9% saline, glucagon:exenatide and glucagon

    Measured: Comparison between infusions (placebo vs drug) over a maximum period of 16 weeks

  8. Part A/B - Glucagon

    Difference in glucagon between 0.9% saline, glucagon:exenatide and glucagon

    Measured: Comparison between infusions (placebo vs drug) over a maximum period of 16 weeks

  9. Part A/B - Insulin

    Difference in insulin between 0.9% saline, glucagon:exenatide and glucagon

    Measured: Comparison between infusions (placebo vs drug) over a maximum period of 16 weeks

  10. Part A/B - C-peptide

    Difference in C-peptide between 0.9% saline, glucagon:exenatide and glucagon

    Measured: Comparison between infusions (placebo vs drug) over a maximum period of 16 weeks

  11. Part A/B - fatty acids

    Difference in fatty acids between 0.9% saline, glucagon:exenatide and glucagon

    Measured: Comparison between infusions (placebo vs drug) over a maximum period of 16 weeks

  12. Part A/B - exenatide

    Difference in exenatide between 0.9% saline, glucagon:exenatide and glucagon

    Measured: Comparison between infusions (placebo vs drug) over a maximum period of 16 weeks

  13. Part A/B - Total GLP-1 and total active GLP-1

    Difference in GLP-1 between 0.9% saline, glucagon:exenatide and glucagon

    Measured: Comparison between infusions (placebo vs drug) over a maximum period of 16 weeks

  14. Part A/B - gastric inhibitory polypeptide

    Difference in gastric inhibitory polypeptide between 0.9% saline, glucagon:exenatide and glucagon

    Measured: Comparison between infusions (placebo vs drug) over a maximum period of 16 weeks

Timeline

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

  1. First posted13 Mar 2020
  2. Study start18 Jan 2022
  3. Primary completion7 Oct 2022
  4. Study completion7 Oct 2022

Resources

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
Randomised
Intervention model
Single group
Model description
Single-centre, single-blinded, physiological pilot study
Masking
Single blind
Who is masked
Participant
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04307797
Sponsor's protocol ID
COCONUT
Acronym
COCONUT
Status last verified
Sep 2024
First submitted
19 Feb 2020
Last updated
19 Sep 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing 0.9% Sodium-chloride, Exenatide (50ng/min for 30 minutes loading followed by 25ng/min maintenance) and glucagon 12.5ng/kg/min and Glucagon 12.5ng/kg/min and 0.9% saline in people with Type 2 Diabetes and Obesity, run by Cambridge University Hospitals NHS Foundation Trust at 1 site in United Kingdom.

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 5 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 19 Sep 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 Kingdom. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Part A - Myocardial glucose uptake (time frame: Comparison between scans over a maximum period of 16 weeks). The study lists 7 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 NCT04307797.

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 19 Sep 2024.

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