E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with angina pectoris and coronary microvascular dysfunction without significant stenosis og major coronary vessels |
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E.1.1.1 | Medical condition in easily understood language |
Patients with chest pain and dysfunction of the small vessels of the heart, but no significant obstruction of the major vessels of the heart |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065566 |
E.1.2 | Term | Microvascular angina |
E.1.2 | System Organ Class | 100000004849 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 |
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E.2.2 | Secondary objectives of the trial |
To evaluate the effect of Liraglutide on - endothelial function assessed by flow mediated dilation (FMD) of the brachial artery by ultrasound. - cardiac function assessed by speckle tracking echocardiography - Weight loss - Change in body composition assessed by DEXA scan - serological markers
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- 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 coronary flow reserve assessed by echo Doppler flow - BMI≥25kg/m2
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E.4 | Principal exclusion criteria |
- Allergy to dipyridamole, Teofyllamine or Liraglutide - Previous myocardial infarction or revascularization - No episodes of chest pain within 6 months before inclusion - Diabetes (reported, noted in journal or patient on antidiabetic medication) - Other causes of chest discomfort deemed highly likely - LVEF<45 - Significant valvular disease - Congenital heart disease - severe co-morbidity with limited life-expectancy< 1 year - Severe asthma - Severe COPD - Pregnancy (pregnancy test will be done at inclusion) - No use of anticonception although in child-bearing age - physical or mental disability - active cancer - significant renal (eGRF<60) or hepatic co-morbidity - chronic alcohol abuse - atrial fibrillation - AV block>1st degree - chronic or previous acute pancreatitis - inflammatory bowel disease - history of thyroid adenoma/carcinoma - participation in other RCT if relevant for the present study. - Language- or other barrier to giving informed consent - No signed informed consent
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E.5 End points |
E.5.1 | Primary end point(s) |
- Changes in coronary flow reserve assessed by transthoracic doppler stress echocardiography (TTDSE). - Changes in symptoms assessed by Seattle Angina Questionnaire (SAQ)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The endpoints will be evaluated after a control period of approximately 4 weeks not receiving any treatment and after 18 weeks (12 weeks of liraglutide treatment + 2 weeks of weight maintenance diet) |
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E.5.2 | Secondary end point(s) |
- Changes in endothelial function assessed by flow mediated dilation (FMD) of the brachial artery by ultrasound. - Changes in cardiac function assessed by speckle tracking echocardiography - Weight loss - Change in body composition assessed by dual X-ray absoptionmetry (DEXA) scan - Changes in serological markers
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The endpoints will be evaluated after a control period of approximately 4 weeks not receiving treatment and after 18 weeks (12 weeks of liraglutide treatment + 2 weeks of weight maintenance diet) with the exception of the DEXA scan which will only be performed at baseline and after 18 weeks and with the exeption of weight, which will be assessed at each visit after initiation of treatment (7 visits). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |