Condition category
Nutritional, Metabolic, Endocrine
Date applied
12/07/2011
Date assigned
04/08/2011
Last edited
14/01/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Lay summary under review 3

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 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 below to request a patient information sheet

Condition

Left venticular heart failure and Type 2 diabetes mellitus

Intervention

1. Patients are investigated in a supine position throughout the study
2. Patients are randomized to receive either 0.12 pmol/kg/min intravenous exenatide or placebo during a 6 hour infusion
3. 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
4. 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 measures

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

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 8 616 10 00
david.nathanson@sodersjukhuset.se

Sponsor type

Hospital/treatment centre

Website

http://www.sodersjukhuset.se/

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

Results - basic reporting

Publication summary

2012 results in: http://www.ncbi.nlm.nih.gov/pubmed/22246377
2016 results in: http://www.ncbi.nlm.nih.gov/pubmed/26759609

Publication citations

  1. 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.

  2. 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.

Additional files

Editorial Notes

14/01/2016: Publication reference added.