Plain English Summary
Background and study aims
The hormone glucagon-like peptide-1 (GLP-1) may have a beneficial effect on heart function beside its well-known action of lowering blood sugar. It was recently shown that GLP-1 improves left ventricular hemodynamics (heart blood flow) in dogs with advanced dilated cardiomyopathy (enlarged heart). This was accompanied by an increase in myocardium (heart muscle) uptake of glucose, without any change in levels of insulin, suggesting that GLP-1 has an insulin-like effect on the myocardium. Some human studies also demonstrate beneficial effects of GLP-1 on the heart. Short-term treatment with GLP-1 of patients with acute myocardial infarction (heart attack) improves heart function, as does long-term treatment of patients with congestive heart failure (CHF). The aim of this study is to find out whether the drug exenatide, which mimics GLP-1, improves hemodynamic functions in type 2 diabetic patients with CHF.
Who can participate?
Type 2 diabetic patients aged 18-80 with heart failure
What does the study involve?
Participants are randomly allocated to be treated with either exenatide or placebo (dummy drug) over 6 hours. After a break of 18 hours, they are treated with the other drug for another 6 hours. Heart function and blood pressure are monitored during the study. Blood samples are taken at the start of the study, at 30 minutes and every hour until 6 hours to measure blood levels of exenatide.
What are the possible benefits and risks of participating?
Not provided at time of registration
Where is the study run from?
Stockholm South General Hospital (Södersjukhuset AB) (Sweden)
When is the study starting and how long is it expected to run for?
January 2008 to June 2010
Who is funding the study?
Eli Lilly Amylin Alliance (USA)
Who is the main contact?
Dr David Nathanson
david.nathanson@sodersjukhuset.se
Trial website
Contact information
Type
Scientific
Primary contact
Dr David Nathanson
ORCID ID
Contact details
Karolinska Institutet
Department of Clinical Science and Education
Division of Internal Medicine
Diabetes Research Stockholm South General Hospital (Södersjukhuset AB)
Stockholm
11883
Sweden
+46 (0)86 16 34 49
david.nathanson@sodersjukhuset.se
Additional identifiers
EudraCT number
2006-005220-16
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
Scientific title
A double-blinded cross-over clinical trial investigating hemodynamic effects of exenatide on diabetic patients hospitalized for congestive heart failure
Acronym
Study hypothesis
Investigate whether exenatide improves hemodynamic functions in type 2 diabetic patients with chronical left ventricular heart failure and the safety of this drug in an acute setting.
Ethics approval
Swedish Central Ethical Review Board, 01/09/2009, ref: MPA 151:2007/25520
Study design
Single-center randomized two-period crossover double-blind study
Primary study design
Interventional
Secondary study design
Randomised cross over trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
Left venticular heart failure and Type 2 diabetes mellitus
Intervention
Patients are investigated in a supine position throughout the study. Patients are randomized to receive either 0.12 pmol/kg/min intravenous exenatide or placebo during a 6 hour infusion. After a wash-out period of 18 hours, another 6 hour infusion of either exenatide and placebo is given, i.e. patients are there own controls. During the study, heart function and invasive arterial blood pressure are monitored with a pulmonary artery catheter (Schwann-Ganz) and a catheter with an arterial line, respectively.
Intervention type
Drug
Phase
Not Applicable
Drug names
Exenatide
Primary outcome measure
1. Serum biomarkers like BNP, NEFA, plasma glucose, S-insulin, S-C-peptide are monitored at multiple time points during the infusions
2. Serum levels of exenatide as follows:
2.1. During infusion (exenatide vs placebo), CI and PCWP are measured at baseline, 1 hour, 3 hours and 6 hours.
2.2. During the 18 hour washout period, another two measurements are made and infusion is repeated (exenatide vs placebo) with new measurements (baseline, 1 hour, 3 hours and 6 hours)
2.3. Blood samples are drawn at baseline (0) and at 30 min and every hour, until 6 hours (totally 7 blood samples are drawn)
Secondary outcome measures
1. Mean arterial blood pressure
2. Mean pulmonary arterial pressure
3. Tolerability of exenatide in this acute setting
Overall trial start date
31/01/2008
Overall trial end date
16/06/2010
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Type 2 diabetes patients with LVHF and NYHA class III or IV symptoms of heart failure who are admitted to the hospital for management of decompensated chronic heart failure
2. A stable period of 24 hours using established therapy, i.e. ACE/ARB-inhibitors, beta-blockers, aldosterone-inhibitors and diuretics
3. Patients who are monitored with a pulmonary artery catheter for clinical purposes
4. In subjects without known diabetes, diabetes will be confirmed by at least two fasting plasma glucose levels exceeding 7 mmol/l or a random plasmaglucose exceeding 11,0 mmol/l according to the American Diabetes Association definition of diabetes
5. Male and female subjects
6. 18-80 years of age
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
20
Participant exclusion criteria
1. Type 1 diabetes (autoantibody positive)
2. Need of inotropic agents, nitroglycerin-infusion or aortic balloon device
3. Unstable LVHF despite maximal oral treatments and i.v. diuretics
4. Significant ischemic heart disease (defined as angina-limited exercise or unstable angina); documented acute myocardial infarction (MI) within the previous 8 weeks
5. Active myocarditis; malfunctioning artificial heart valve
6. Symptomatic primary pulmonary disease; serious arrhythmias, defined as a history of ventricular flutter or fibrillation other than that occurring within 24 hours after acute MI
7. History of sudden cardiac death or symptomatic ventricular tachycardia within 3 months before study entry; second or third degree atrioventricular block, unless the patient has a functioning implanted pacemaker
8. Supine systolic blood pressure <85 mm Hg or >200 mm Hg
9. Primary renal impairment (creatinine clearance < 30 ml/min)
10. Uncorrected hypokalemia or hyperkalemia (potassium <3.5 mmol/l or >5.5 mmol/l)
11. Significant anemia (Hb < 90 g/l), or treatment with another investigational agent within 30 days before study entry
12. Severe gastrointestinal disease, including gastroparesis
13. Pregnancy or lactation
14. History of drug abuse
15. Presence or history of allergic reaction or intolerance to multiple drugs
16. Subjects considered by the Investigator as unsuitable candidates to receive an investigational drug
17. Known history of, or concomitant medical condition that might interfere with the evaluation of study medication
18. No minor subjects (<18 years of age) or pregnant women will be participating in the study
Recruitment start date
31/01/2008
Recruitment end date
16/06/2010
Locations
Countries of recruitment
Sweden
Trial participating centre
Karolinska Institutet
Stockholm
11883
Sweden
Sponsor information
Organisation
Stockholm South General Hospital (Södersjukhuset AB) (Sweden)
Sponsor details
c/o Dr David Nathanson
Karolinska Institutet
Department of Clinical Science and Education
Division of Internal Medicine Diabetes Research
Stockholm
118 83
Sweden
+46 (0)8 616 10 00
david.nathanson@sodersjukhuset.se
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Industry
Funder name
Eli Lilly Amylin Alliance (USA)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2012 results in: http://www.ncbi.nlm.nih.gov/pubmed/22246377
2016 results in: http://www.ncbi.nlm.nih.gov/pubmed/26759609
Publication citations
-
Results
Nathanson D, Ullman B, Löfström U, Hedman A, Frick M, Sjöholm A, Nyström T, Effects of intravenous exenatide in type 2 diabetic patients with congestive heart failure: a double-blind, randomised controlled clinical trial of efficacy and safety., Diabetologia, 2012, 55, 4, 926-935, doi: 10.1007/s00125-011-2440-x.
-
Results
D Nathanson, M Frick, B Ullman, T Nyström, Exenatide infusion decreases atrial natriuretic peptide levels by reducing cardiac filling pressures in type 2 diabetes patients with decompensated congestive heart failure, Diabetol Metab Syndr, 2016, 8, 5, doi: 10.1186/s13098-015-0116-2.