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Trial · Interventional

CompletedPhase 4Registry data

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

Short name COCONUT

NCTNCT04307797 (opens ClinicalTrials.gov in a new tab)Other idCOCONUT
Open at ClinicalTrials.govAsk about this trial

Overview

Status
Completed
Phase
Phase 4
Enrollment
10 participants (actual)
Sponsor
Cambridge University Hospitals NHS Foundation Trust · Other
Design
Randomized · Single masking
Countries
1 country

United Kingdom

Start
18 Jan 2022
Primary completion
7 Oct 2022
Completion
7 Oct 2022
First posted
13 Mar 2020
Last update posted
19 Sept 2024
Conditions
Type 2 Diabetes · Obesity

Timeline

1 trial · 1 completed

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
20222023
  1. Ph 4

    COCONUT

    NCT04307797

    18 Jan 2022 to 7 Oct 2022

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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

Interventions

  • 0.9% Sodium-chlorideDrug
  • Exenatide (50ng/min for 30 minutes loading followed by 25ng/min maintenance) and glucagon 12.5ng/kg/minDrug
  • Glucagon 12.5ng/kg/min and 0.9% salineDrug
  • 0.9% Sodium-chlorideDrug
  • Exenatide (50ng/min for 30 minutes loading followed by 25ng/min maintenance) and glucagon 12.5ng/kg/minDrug
  • Glucagon 12.5ng/kg/minDrug

Arms0

The registry lists no arms for this trial.

Primary outcomes7

Outcomes the sponsor listed as primary.

  1. Part A - Myocardial glucose uptake

    Time frame · Comparison between scans over a maximum period of 16 weeks

    Registry description

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

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

    Time frame · Comparison between scans over a maximum period of 16 weeks

    Registry description

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

  3. Part A - Ejection fraction

    Time frame · Comparison between scans over a maximum period of 16 weeks

    Registry description

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

  4. Part A - Stroke volume

    Time frame · Comparison between scans over a maximum period of 16 weeks

    Registry description

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

  5. Part A - Cardiac output

    Time frame · Comparison between scans over a maximum period of 16 weeks

    Registry description

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

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

    Time frame · Comparison between scans over a maximum period of 16 weeks

    Registry description

    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)

  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)

    Time frame · Comparison between scans over a maximum period of 16 weeks

    Registry description

    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)

Secondary outcomes(14)

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

    Time frame · Comparison between scans over a maximum period of 16 weeks

    Registry description

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

  2. Part A - Radial strain

    Time frame · Comparison between scans over a maximum period of 16 weeks

    Registry description

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

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

    Time frame · Comparison between scans over a maximum period of 16 weeks

    Registry description

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

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

    Time frame · Comparison between scans over a maximum period of 16 weeks

    Registry description

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

  5. Part A/B - Heart rate

    Time frame · Comparison between infusions (placebo vs drug) over a maximum period of 16 weeks

    Registry description

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

  6. Part A/B - Blood pressure

    Time frame · Comparison between infusions (placebo vs drug) over a maximum period of 16 weeks

    Registry description

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

  7. Part A/B - Glucose

    Time frame · Comparison between infusions (placebo vs drug) over a maximum period of 16 weeks

    Registry description

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

  8. Part A/B - Glucagon

    Time frame · Comparison between infusions (placebo vs drug) over a maximum period of 16 weeks

    Registry description

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

  9. Part A/B - Insulin

    Time frame · Comparison between infusions (placebo vs drug) over a maximum period of 16 weeks

    Registry description

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

  10. Part A/B - C-peptide

    Time frame · Comparison between infusions (placebo vs drug) over a maximum period of 16 weeks

    Registry description

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

  11. Part A/B - fatty acids

    Time frame · Comparison between infusions (placebo vs drug) over a maximum period of 16 weeks

    Registry description

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

  12. Part A/B - exenatide

    Time frame · Comparison between infusions (placebo vs drug) over a maximum period of 16 weeks

    Registry description

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

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

    Time frame · Comparison between infusions (placebo vs drug) over a maximum period of 16 weeks

    Registry description

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

  14. Part A/B - gastric inhibitory polypeptide

    Time frame · Comparison between infusions (placebo vs drug) over a maximum period of 16 weeks

    Registry description

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

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

No results are posted for this trial.

Completed trials do not always post results.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years up to 99 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria: * 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 Exclusion Criteria: * 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) * 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

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