Glucagon-like Peptide-1 and Coronary Microvascular Dysfunction in Women With Angina Pectoris and no Coronary Stenosis

NCT02602600 | Completed Phase 4 DMC

• 1 other identifier: GAP
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of the present study is to evaluate the effect of treatment with Liraglutide on the coronary microvasculature and angina symptoms, in overweight patients with microvascular dysfunction and angina pectoris but no coronary artery stenosis.

Conditions

Microvascular Angina

Outcome Measures

Primary Outcomes (2)

• Change from baseline in Coronary Flow Reserve

  Assessed by transthoracic doppler stress echocardiography

  Assessed at baseline, week 4 and week 18

• Change from baseline in Angina Symptoms

  Assessed by the Seattle Angina Questionnaire

  Assessed at baseline, week 4 and week 18

Secondary Outcomes (4)

• Change in endothelial function

  Assessed at baseline, week 4 and week 18

• Change in cardiac function

  Assessed at baseline, week 4 and week 18

• Change in body weight

  Assessed at baseline, week 4 and week 18

• Change in body composition

  Assessed before and after treatment (week 4 and week 18)

Study Arms (1)

Liraglutide

EXPERIMENTAL

Liraglutide up to 3.0 mg daily injected subcutaneously (minimum 1.2 mg daily) for 12 weeks followed by 2 weeks of weight maintenance diet. Before initiating treatment participants will serve as their own controls for 4 weeks.

Drug: Liraglutide

Interventions

Liraglutide DRUG

* Liraglutide up to 3 mg daily injected subcutaneously (minimum 1.2 mg daily) for 12 weeks. * Weight maintenance diet for 2 weeks

Also known as: Victoza

Liraglutide

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women aged 40-75 with angina-like symptoms assessed by the Seattle Angina Questionnaire (SAQ).
• Women aged 40-75 with angina-like symptoms assessed by the Seattle Angina Questionnaire (SAQ).
• Referred for ischemic heart disease (IHD) assessment with no significant coronary stenosis (\>50%) at coronary angiography or CT-angiography
• Impaired CFR assessed by echo Doppler flow (defined ratio≤2,5).
• BMI≥25kg/m2

You may not qualify if:

• Allergy to dipyridamole, theophyllamine or liraglutide
• Previous myocardial infarction or revascularization
• Diabetes (reported, noted in journal or patient on antidiabetic medication)
• Other causes of chest discomfort deemed highly likely
• Left ventricular ejection fraction \<45
• Significant valvular disease
• Congenital heart disease
• severe co-morbidity with limited life-expectancy\< 1 year
• Severe asthma
• Severe chronic obstructive pulmonary disease
• physical or mental disability
• active cancer
• significant renal (eGRF\<30) or hepatic co-morbidity
• chronic alcohol abuse
• atrial fibrillation

Sponsors & Collaborators

• Eva Prescott: lead

Study Sites (1)

Bispebjerg University Hospital

Copenhagen, Copenhagen Northwest, 2400, Denmark

Location

Related Publications (23)

• Patel MR, Peterson ED, Dai D, Brennan JM, Redberg RF, Anderson HV, Brindis RG, Douglas PS. Low diagnostic yield of elective coronary angiography. N Engl J Med. 2010 Mar 11;362(10):886-95. doi: 10.1056/NEJMoa0907272.

  PMID: 20220183 RESULT

• Jespersen L, Hvelplund A, Abildstrom SZ, Pedersen F, Galatius S, Madsen JK, Jorgensen E, Kelbaek H, Prescott E. Stable angina pectoris with no obstructive coronary artery disease is associated with increased risks of major adverse cardiovascular events. Eur Heart J. 2012 Mar;33(6):734-44. doi: 10.1093/eurheartj/ehr331. Epub 2011 Sep 11.

  PMID: 21911339 RESULT

• Johnson BD, Shaw LJ, Pepine CJ, Reis SE, Kelsey SF, Sopko G, Rogers WJ, Mankad S, Sharaf BL, Bittner V, Bairey Merz CN. Persistent chest pain predicts cardiovascular events in women without obstructive coronary artery disease: results from the NIH-NHLBI-sponsored Women's Ischaemia Syndrome Evaluation (WISE) study. Eur Heart J. 2006 Jun;27(12):1408-15. doi: 10.1093/eurheartj/ehl040. Epub 2006 May 23.

  PMID: 16720691 RESULT

• Gulati M, Cooper-DeHoff RM, McClure C, Johnson BD, Shaw LJ, Handberg EM, Zineh I, Kelsey SF, Arnsdorf MF, Black HR, Pepine CJ, Merz CN. Adverse cardiovascular outcomes in women with nonobstructive coronary artery disease: a report from the Women's Ischemia Syndrome Evaluation Study and the St James Women Take Heart Project. Arch Intern Med. 2009 May 11;169(9):843-50. doi: 10.1001/archinternmed.2009.50.

  PMID: 19433695 RESULT

• Pepine CJ, Anderson RD, Sharaf BL, Reis SE, Smith KM, Handberg EM, Johnson BD, Sopko G, Bairey Merz CN. Coronary microvascular reactivity to adenosine predicts adverse outcome in women evaluated for suspected ischemia results from the National Heart, Lung and Blood Institute WISE (Women's Ischemia Syndrome Evaluation) study. J Am Coll Cardiol. 2010 Jun 22;55(25):2825-32. doi: 10.1016/j.jacc.2010.01.054.

  PMID: 20579539 RESULT

• Reis SE, Holubkov R, Conrad Smith AJ, Kelsey SF, Sharaf BL, Reichek N, Rogers WJ, Merz CN, Sopko G, Pepine CJ; WISE Investigators. Coronary microvascular dysfunction is highly prevalent in women with chest pain in the absence of coronary artery disease: results from the NHLBI WISE study. Am Heart J. 2001 May;141(5):735-41. doi: 10.1067/mhj.2001.114198.

  PMID: 11320360 RESULT

• Camici PG, Crea F. Coronary microvascular dysfunction. N Engl J Med. 2007 Feb 22;356(8):830-40. doi: 10.1056/NEJMra061889. No abstract available.

  PMID: 17314342 RESULT

• Jespersen L, Abildstrom SZ, Hvelplund A, Madsen JK, Galatius S, Pedersen F, Hojberg S, Prescott E. Burden of hospital admission and repeat angiography in angina pectoris patients with and without coronary artery disease: a registry-based cohort study. PLoS One. 2014 Apr 4;9(4):e93170. doi: 10.1371/journal.pone.0093170. eCollection 2014.

  PMID: 24705387 RESULT

• Di Franco A, Villano A, Di Monaco A, Lamendola P, Russo G, Stazi A, Scavone G, Nerla R, Sestito A, Lanza GA, Crea F. Correlation between coronary microvascular function and angina status in patients with stable microvascular angina. Eur Rev Med Pharmacol Sci. 2014;18(3):374-9.

  PMID: 24563437 RESULT

• Ussher JR, Drucker DJ. Cardiovascular actions of incretin-based therapies. Circ Res. 2014 May 23;114(11):1788-803. doi: 10.1161/CIRCRESAHA.114.301958.

  PMID: 24855202 RESULT

• Nikolaidis LA, Elahi D, Hentosz T, Doverspike A, Huerbin R, Zourelias L, Stolarski C, Shen YT, Shannon RP. Recombinant glucagon-like peptide-1 increases myocardial glucose uptake and improves left ventricular performance in conscious dogs with pacing-induced dilated cardiomyopathy. Circulation. 2004 Aug 24;110(8):955-61. doi: 10.1161/01.CIR.0000139339.85840.DD. Epub 2004 Aug 16.

  PMID: 15313949 RESULT

• 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.

  PMID: 18427132 RESULT

• Noyan-Ashraf MH, Momen MA, Ban K, Sadi AM, Zhou YQ, Riazi AM, Baggio LL, Henkelman RM, Husain M, Drucker DJ. GLP-1R agonist liraglutide activates cytoprotective pathways and improves outcomes after experimental myocardial infarction in mice. Diabetes. 2009 Apr;58(4):975-83. doi: 10.2337/db08-1193. Epub 2009 Jan 16.

  PMID: 19151200 RESULT

• Lonborg J, Kelbaek H, Vejlstrup N, Botker HE, Kim WY, Holmvang L, Jorgensen E, Helqvist S, Saunamaki K, Terkelsen CJ, Schoos MM, Kober L, Clemmensen P, Treiman M, Engstrom T. Exenatide reduces final infarct size in patients with ST-segment-elevation myocardial infarction and short-duration of ischemia. Circ Cardiovasc Interv. 2012 Apr;5(2):288-95. doi: 10.1161/CIRCINTERVENTIONS.112.968388. Epub 2012 Apr 10.

  PMID: 22496084 RESULT

• Woo JS, Kim W, Ha SJ, Kim JB, Kim SJ, Kim WS, Seon HJ, Kim KS. Cardioprotective effects of exenatide in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention: results of exenatide myocardial protection in revascularization study. Arterioscler Thromb Vasc Biol. 2013 Sep;33(9):2252-60. doi: 10.1161/ATVBAHA.113.301586. Epub 2013 Jul 18.

  PMID: 23868944 RESULT

• McCormick LM, Kydd AC, Read PA, Ring LS, Bond SJ, Hoole SP, Dutka DP. Chronic dipeptidyl peptidase-4 inhibition with sitagliptin is associated with sustained protection against ischemic left ventricular dysfunction in a pilot study of patients with type 2 diabetes mellitus and coronary artery disease. Circ Cardiovasc Imaging. 2014 Mar;7(2):274-81. doi: 10.1161/CIRCIMAGING.113.000785. Epub 2014 Feb 6.

  PMID: 24503784 RESULT

• Read PA, Khan FZ, Heck PM, Hoole SP, Dutka DP. DPP-4 inhibition by sitagliptin improves the myocardial response to dobutamine stress and mitigates stunning in a pilot study of patients with coronary artery disease. Circ Cardiovasc Imaging. 2010 Mar;3(2):195-201. doi: 10.1161/CIRCIMAGING.109.899377. Epub 2010 Jan 14.

  PMID: 20075143 RESULT

• Read PA, Hoole SP, White PA, Khan FZ, O'Sullivan M, West NE, Dutka DP. A pilot study to assess whether glucagon-like peptide-1 protects the heart from ischemic dysfunction and attenuates stunning after coronary balloon occlusion in humans. Circ Cardiovasc Interv. 2011 Jun;4(3):266-72. doi: 10.1161/CIRCINTERVENTIONS.110.960476. Epub 2011 May 17.

  PMID: 21586690 RESULT

• Read PA, Khan FZ, Dutka DP. Cardioprotection against ischaemia induced by dobutamine stress using glucagon-like peptide-1 in patients with coronary artery disease. Heart. 2012 Mar;98(5):408-13. doi: 10.1136/hrt.2010.219345. Epub 2011 May 10.

  PMID: 21561896 RESULT

• 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.

  PMID: 14981009 RESULT

• Faber R, Zander M, Pena A, Michelsen MM, Mygind ND, Prescott E. Effect of the glucagon-like peptide-1 analogue liraglutide on coronary microvascular function in patients with type 2 diabetes - a randomized, single-blinded, cross-over pilot study. Cardiovasc Diabetol. 2015 Apr 22;14:41. doi: 10.1186/s12933-015-0206-3.

  PMID: 25896352 RESULT

• Pedersen LR, Olsen RH, Jurs A, Astrup A, Chabanova E, Simonsen L, Wisloff U, Haugaard SB, Prescott E. A randomised trial comparing weight loss with aerobic exercise in overweight individuals with coronary artery disease: The CUT-IT trial. Eur J Prev Cardiol. 2015 Aug;22(8):1009-17. doi: 10.1177/2047487314545280. Epub 2014 Jul 31.

  PMID: 25082954 RESULT

• Suhrs HE, Raft KF, Bove K, Madsbad S, Holst JJ, Zander M, Prescott E. Effect of liraglutide on body weight and microvascular function in non-diabetic overweight women with coronary microvascular dysfunction. Int J Cardiol. 2019 May 15;283:28-34. doi: 10.1016/j.ijcard.2018.12.005. Epub 2019 Jan 2.

  PMID: 30773266 DERIVED

MeSH Terms

Conditions

Microvascular Angina

Interventions

Liraglutide

Condition Hierarchy (Ancestors)

Angina Pectoris; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Eva IB Prescott, MD, DMSc

  Bispebjerg Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, DMSc

Study Record Dates

• First Submitted: November 8, 2015
• First Posted: November 11, 2015
• Study Start: November 19, 2015
• Primary Completion: April 18, 2017
• Study Completion: April 18, 2017
• Last Updated: July 11, 2018

Record last verified: 2018-07

Locations

DK (1)