Type 2 Diabetes MellitusNCT00923962

Endothelial and Metabolic Effects of Glucagon-like Peptide-1 (GLP-1) in Coronary Circulation in Patients With Type 2 Diabetes Mellitus

A study testing Glucagon like peptide-1 and Adenosine in people with Type 2 Diabetes Mellitus, run by University Hospital, Gentofte, Copenhagen at 1 site in Denmark.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

GLP-1 is an incretin hormone which is discharged from the intestines after food intake. The hormone is known for its powerful insulinotropic and trophic effects on the beta cells in the pancreas and is currently used as an anti-diabetic agent in patients with type 2 diabetes (T2DM). Read more about this study

Who is it for?: Ages 18 to 75 yearsHealthy volunteers can take part
Conditions the study is for: Type 2 Diabetes Mellitus
What is being tested?: Glucagon like peptide-1 and Adenosine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 35 participants
Where: 1 siteDenmark
Study dates: Jun 2009to Jan 2012
Phase: Interventional
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 75 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

Caucasians over 18
Emitted for non-acute coronary arteriography (CAG) in Gentofte hospital
BMI 23-35 kg/m2
Normal hemoglobin
Who gives informed consent
Those with type 2 diabetes: HbA1c 6-10%
Those without type 2 diabetes: Normal oral glucose tolerance test (OGTT) according to WHO criteria

Who cannot join

Liver disease (ALAT > 2x normal)
Diabetic nefropati (Creatinine > 130 µM or albuminuria)
Treatment with medicine that cannot be paused 12 hours before intervention
Pregnancy or breastfeeding
Insulin- or glitazone treatment
Healthy controls: close family history with diabetes

Show all 13Show fewer

Unstable angina pectoris
Non-STEMI
Atrial fibrillation
Valvular disease
LVEF < 50%
Severe systemic disease
Type 1 diabetes

Trial locations and contacts

1 site in 1 country.

Denmark1 site

University Hospital Gentofte, Department of Cardiology
Gentofte Municipality, 2900

Other trials in Denmark

About this study

Official title: Endothelial and Metabolic Effects of GLP-1 in Coronary Circulation in Patients With Type 2 Diabetes Mellitus

GLP-1 receptors are widely distributed including on the endothelial cells in both coronary and skeletal muscle circulation and on the myocardium. GLP-1-receptor studies on knock-out mice have shown that they exhibit a reduced myocardial contractility and reduced diastolic heart function. GLP-1 also shows beneficial cardiovascular effects in patients with acute myocardial infarctions and dogs with dilated cardiomyopathy in that the left ventricle function and endothelial dysfunction improves after GLP-1 treatment via insulin-independent mechanisms. Preclinical studies indicate that exogenous administrated GLP-1 in physiological concentrations can improve perfusion but this has never been tested in humans. It is also unknown whether GLP-1 can directly increase the glucose/metabolite uptake across both cardiac and skeletal muscle in an insulin independent manner. Unpublished studies do however indicate that the improvement in the cardiovascular system is largely dependent upon a high blood glucose level and only partially dependent upon the antiglycemic effects of GLP-1.

In the proposed studies the investigators wish to examine the physiological role of GLP-1 receptor stimulation both with regard to perfusion, metabolic improvement as well as cardiac inotropic. These studies will be conducted in both healthy and in T2DM patients.

Conditions: Type 2 Diabetes Mellitus
Being tested: Glucagon like peptide-1, Adenosine
Keywords: Basic science, Type 2 Diabetes mellitus, Glucagon like peptid-1, Coronary Bloodflow, Metabolite uptake
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.

Glucagon like peptide-1Drug
0,1 pmol/kg/min
AdenosineDrug
20-40 microgram/minute

Study groups in NCT00923962
Study group	Role	What they receive
Type 2 Diabetes patients	Active comparator	Not described Receives: Drug: Glucagon like peptide-1; Drug: Adenosine
Healthy	Active comparator	Not described Receives: Drug: Glucagon like peptide-1; Drug: Adenosine
Artherosclerosis	Active comparator	Not described Receives: Drug: Glucagon like peptide-1; Drug: Adenosine

What is being measured

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

Coronary blood flow
Measured: 10 minutes after I.A. GLP-1
Coronary metabolite uptake
Measured: 10 minutes after I.A. GLP-1

Timeline

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

Jun 2009Jan 2012

First posted18 Jun 2009 (estimated)
Study startJun 2009
Primary completionJan 2012
Study completionJan 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (16)Papers the sponsor has linked to this study.
Other trials for Type 2 Diabetes MellitusStudies of the same condition, open and under way.
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 N/A
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 35 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00923962
Sponsor's protocol ID: GLP-1 Coronary circulation 01
Status last verified: Sep 2012
First submitted: 17 Jun 2009
Last updated: 18 Sep 2012
Results posted: No
Data monitoring committee: No

Publications

Bjallmark A, Larsson M, Winter R, Westholm C, Jacobsen P, Lind B, Brodin LA. Velocity tracking--a novel method for quantitative analysis of longitudinal myocardial function. J Am Soc Echocardiogr. 2007 Jul;20(7):847-56. doi: 10.1016/j.echo.2006.11.024.
PubMed 17617311
Diamant M, Lamb HJ, Groeneveld Y, Endert EL, Smit JW, Bax JJ, Romijn JA, de Roos A, Radder JK. Diastolic dysfunction is associated with altered myocardial metabolism in asymptomatic normotensive patients with well-controlled type 2 diabetes mellitus. J Am Coll Cardiol. 2003 Jul 16;42(2):328-35. doi: 10.1016/s0735-1097(03)00625-9.
PubMed 12875772
Edwards CM, Todd JF, Mahmoudi M, Wang Z, Wang RM, Ghatei MA, Bloom SR. Glucagon-like peptide 1 has a physiological role in the control of postprandial glucose in humans: studies with the antagonist exendin 9-39. Diabetes. 1999 Jan;48(1):86-93. doi: 10.2337/diabetes.48.1.86.
PubMed 9892226
Golpon HA, Puechner A, Welte T, Wichert PV, Feddersen CO. Vasorelaxant effect of glucagon-like peptide-(7-36)amide and amylin on the pulmonary circulation of the rat. Regul Pept. 2001 Dec 15;102(2-3):81-6. doi: 10.1016/s0167-0115(01)00300-7.
PubMed 11730979
Luque MA, Gonzalez N, Marquez L, Acitores A, Redondo A, Morales M, Valverde I, Villanueva-Penacarrillo ML. Glucagon-like peptide-1 (GLP-1) and glucose metabolism in human myocytes. J Endocrinol. 2002 Jun;173(3):465-73. doi: 10.1677/joe.0.1730465.
PubMed 12065236
Mogelvang R, Sogaard P, Pedersen SA, Olsen NT, Schnohr P, Jensen JS. Tissue Doppler echocardiography in persons with hypertension, diabetes, or ischaemic heart disease: the Copenhagen City Heart Study. Eur Heart J. 2009 Mar;30(6):731-9. doi: 10.1093/eurheartj/ehn596. Epub 2009 Jan 27.
PubMed 19176536
Nichols GA, Hillier TA, Erbey JR, Brown JB. Congestive heart failure in type 2 diabetes: prevalence, incidence, and risk factors. Diabetes Care. 2001 Sep;24(9):1614-9. doi: 10.2337/diacare.24.9.1614.
PubMed 11522708
Nikolaidis LA, Mankad S, Sokos GG, Miske G, Shah A, Elahi D, Shannon RP. Effects of glucagon-like peptide-1 in patients with acute myocardial infarction and left ventricular dysfunction after successful reperfusion. Circulation. 2004 Mar 2;109(8):962-5. doi: 10.1161/01.CIR.0000120505.91348.58. Epub 2004 Feb 23.
PubMed 14981009
Yu M, Moreno C, Hoagland KM, Dahly A, Ditter K, Mistry M, Roman RJ. Antihypertensive effect of glucagon-like peptide 1 in Dahl salt-sensitive rats. J Hypertens. 2003 Jun;21(6):1125-35. doi: 10.1097/00004872-200306000-00012.
PubMed 12777949
Nystrom T, Gutniak MK, Zhang Q, Zhang F, Holst JJ, Ahren B, Sjoholm A. Effects of glucagon-like peptide-1 on endothelial function in type 2 diabetes patients with stable coronary artery disease. Am J Physiol Endocrinol Metab. 2004 Dec;287(6):E1209-15. doi: 10.1152/ajpendo.00237.2004. Epub 2004 Sep 7.
PubMed 15353407
Bullock BP, Heller RS, Habener JF. Tissue distribution of messenger ribonucleic acid encoding the rat glucagon-like peptide-1 receptor. Endocrinology. 1996 Jul;137(7):2968-78. doi: 10.1210/endo.137.7.8770921.
PubMed 8770921
Wei Y, Mojsov S. Tissue-specific expression of the human receptor for glucagon-like peptide-I: brain, heart and pancreatic forms have the same deduced amino acid sequences. FEBS Lett. 1995 Jan 30;358(3):219-24. doi: 10.1016/0014-5793(94)01430-9.
PubMed 7843404
Wei Y, Mojsov S. Distribution of GLP-1 and PACAP receptors in human tissues. Acta Physiol Scand. 1996 Jul;157(3):355-7. doi: 10.1046/j.1365-201X.1996.42256000.x. No abstract available.
PubMed 8830893
Nikolaidis LA, Elahi D, Shen YT, Shannon RP. Active metabolite of GLP-1 mediates myocardial glucose uptake and improves left ventricular performance in conscious dogs with dilated cardiomyopathy. Am J Physiol Heart Circ Physiol. 2005 Dec;289(6):H2401-8. doi: 10.1152/ajpheart.00347.2005. Epub 2005 Jul 15.
PubMed 16024574
Ban K, Noyan-Ashraf MH, Hoefer J, Bolz SS, Drucker DJ, Husain M. Cardioprotective and vasodilatory actions of glucagon-like peptide 1 receptor are mediated through both glucagon-like peptide 1 receptor-dependent and -independent pathways. Circulation. 2008 May 6;117(18):2340-50. doi: 10.1161/CIRCULATIONAHA.107.739938. Epub 2008 Apr 21.
PubMed 18427132

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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All Type 2 Diabetes Mellitus trials

Study at a glance

From the registry record, last updated by the sponsor on 18 Sep 2012. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Endothelial and Metabolic Effects of GLP-1 in Coronary Circulation in Patients With Type 2 Diabetes Mellitus
ClinicalTrials.gov ID: NCT00923962
Acronym / sponsor ID: GLP-1 Coronary circulation 01
Conditions: Type 2 Diabetes Mellitus
Keywords: Basic science, Type 2 Diabetes mellitus, Glucagon like peptid-1, Coronary Bloodflow, Metabolite uptake
Study type: Interventional
Recruitment status: Completed
Enrolment: 35 participants (actual)
Lead sponsor: University Hospital, Gentofte, CopenhagenUniversity, hospital or other
Collaborators: Merck Sharp & Dohme LLC
Study start: Jun 2009
Primary completion: Jan 2012 (actual)
Study completion: Jan 2012 (actual)
First posted: 18 Jun 2009 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
Type 2 Diabetes patients	Active comparator	Drug: Glucagon like peptide-1, Drug: Adenosine
Healthy	Active comparator	Drug: Glucagon like peptide-1, Drug: Adenosine
Artherosclerosis	Active comparator	Drug: Glucagon like peptide-1, Drug: Adenosine

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

Caucasians over 18
Emitted for non-acute coronary arteriography (CAG) in Gentofte hospital
BMI 23-35 kg/m2
Normal hemoglobin
Who gives informed consent

Key exclusion criteria (13 listed)

Liver disease (ALAT > 2x normal)
Diabetic nefropati (Creatinine > 130 µM or albuminuria)
Treatment with medicine that cannot be paused 12 hours before intervention
Pregnancy or breastfeeding
Insulin- or glitazone treatment

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
Glucagon like peptide-10,1 pmol/kg/min	Drug	Artherosclerosis, Healthy, Type 2 Diabetes patients
Adenosine20-40 microgram/minute	Drug	Artherosclerosis, Healthy, Type 2 Diabetes patients

Primary outcome

Coronary blood flow
Time frame: 10 minutes after I.A. GLP-1
Coronary metabolite uptake
Time frame: 10 minutes after I.A. GLP-1

Results and safety

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

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2012.
Background: PubMed 17617311Bjallmark A, Larsson M, Winter R, Westholm C, Jacobsen P, Lind B, Brodin LA. Velocity tracking--a novel method for quantitative analysis of longitudinal myocardial function. J Am Soc Echocardiogr. 2007 Jul;20(7):847-56. doi: 10.1016/j.echo.2006.11.024.
Background: PubMed 12875772Diamant M, Lamb HJ, Groeneveld Y, Endert EL, Smit JW, Bax JJ, Romijn JA, de Roos A, Radder JK. Diastolic dysfunction is associated with altered myocardial metabolism in asymptomatic normotensive patients with well-controlled type 2 diabetes mellitus. J Am Coll Cardiol. 2003 Jul 16;42(2):328-35. doi: 10.1016/s0735-1097(03)00625-9.
Background: PubMed 9892226Edwards CM, Todd JF, Mahmoudi M, Wang Z, Wang RM, Ghatei MA, Bloom SR. Glucagon-like peptide 1 has a physiological role in the control of postprandial glucose in humans: studies with the antagonist exendin 9-39. Diabetes. 1999 Jan;48(1):86-93. doi: 10.2337/diabetes.48.1.86.
Background: PubMed 11730979Golpon HA, Puechner A, Welte T, Wichert PV, Feddersen CO. Vasorelaxant effect of glucagon-like peptide-(7-36)amide and amylin on the pulmonary circulation of the rat. Regul Pept. 2001 Dec 15;102(2-3):81-6. doi: 10.1016/s0167-0115(01)00300-7.
Background: PubMed 12065236Luque MA, Gonzalez N, Marquez L, Acitores A, Redondo A, Morales M, Valverde I, Villanueva-Penacarrillo ML. Glucagon-like peptide-1 (GLP-1) and glucose metabolism in human myocytes. J Endocrinol. 2002 Jun;173(3):465-73. doi: 10.1677/joe.0.1730465.
Background: PubMed 19176536Mogelvang R, Sogaard P, Pedersen SA, Olsen NT, Schnohr P, Jensen JS. Tissue Doppler echocardiography in persons with hypertension, diabetes, or ischaemic heart disease: the Copenhagen City Heart Study. Eur Heart J. 2009 Mar;30(6):731-9. doi: 10.1093/eurheartj/ehn596. Epub 2009 Jan 27.
Background: PubMed 11522708Nichols GA, Hillier TA, Erbey JR, Brown JB. Congestive heart failure in type 2 diabetes: prevalence, incidence, and risk factors. Diabetes Care. 2001 Sep;24(9):1614-9. doi: 10.2337/diacare.24.9.1614.
Background: PubMed 14981009Nikolaidis LA, Mankad S, Sokos GG, Miske G, Shah A, Elahi D, Shannon RP. Effects of glucagon-like peptide-1 in patients with acute myocardial infarction and left ventricular dysfunction after successful reperfusion. Circulation. 2004 Mar 2;109(8):962-5. doi: 10.1161/01.CIR.0000120505.91348.58. Epub 2004 Feb 23.
Background: PubMed 12777949Yu M, Moreno C, Hoagland KM, Dahly A, Ditter K, Mistry M, Roman RJ. Antihypertensive effect of glucagon-like peptide 1 in Dahl salt-sensitive rats. J Hypertens. 2003 Jun;21(6):1125-35. doi: 10.1097/00004872-200306000-00012.
Background: PubMed 15353407Nystrom T, Gutniak MK, Zhang Q, Zhang F, Holst JJ, Ahren B, Sjoholm A. Effects of glucagon-like peptide-1 on endothelial function in type 2 diabetes patients with stable coronary artery disease. Am J Physiol Endocrinol Metab. 2004 Dec;287(6):E1209-15. doi: 10.1152/ajpendo.00237.2004. Epub 2004 Sep 7.
Background: PubMed 8770921Bullock BP, Heller RS, Habener JF. Tissue distribution of messenger ribonucleic acid encoding the rat glucagon-like peptide-1 receptor. Endocrinology. 1996 Jul;137(7):2968-78. doi: 10.1210/endo.137.7.8770921.
Background: PubMed 7843404Wei Y, Mojsov S. Tissue-specific expression of the human receptor for glucagon-like peptide-I: brain, heart and pancreatic forms have the same deduced amino acid sequences. FEBS Lett. 1995 Jan 30;358(3):219-24. doi: 10.1016/0014-5793(94)01430-9.

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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.

Jan S Jensen, MD, DMSc study chair

University hospital Gentofte, Department of Cardiology

Jaya Rosenmeier, MD, Ph.D. principal investigator

University hospital Gentofte, Department of Cardiology

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Glucagon like peptide-1 and Adenosine in people with Type 2 Diabetes Mellitus, run by University Hospital, Gentofte, Copenhagen at 1 site in Denmark.

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 7 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 18 Sep 2012. 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 Denmark. 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.

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?

Coronary blood flow (time frame: 10 minutes after I.A. GLP-1). The study lists 2 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 NCT00923962, which also lists 16 linked publications.

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 18 Sep 2012.