Endocardial VEGF-D Gene Therapy for the Treatment of Severe Coronary Heart Disease - A Phase 1 Single-blinded Placebo-controlled Phase 1 Clinical Trial
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Assessments for safety and tolerability as measured as the acute and late adverse effects, laboratory parameters, biodistribution of the vector, anti-adenovirus antibodies and VEGF-levels before and in several time points after the gene transfer.
研究概览
简要总结
The purpose of the study is to evaluate the safety and efficacy of catheter mediated endocardial adenovirus VEGF-D gene therapy in patients with severe coronary heart disease.
详细描述
Study objective(s):
The purpose of the study is to evaluate the safety and efficacy of catheter mediated endocardial adenovirus VEGF-D gene transfer in patients with severe coronary heart disease to whom revascularisation cannot be performed ("no option -patients"). The primary objective is safety of the gene therapy and the secondary objective is the efficacy of gene therapy to improve myocardial perfusion as measured by MRI, PET and left ventricular function as measured by echocardiography as well as to improve functional status as measured by bicycle ergometer test. Quality of life will be monitored with a personal interview and the consumption of nitrate medication.
Study design:
This is a randomised, single-blinded, placebo controlled single centre Phase I study for patients with coronary heart disease to whom no other treatment than standard medication is available. Patients will be randomized 4:1 to the treatment group and control group. Control patients will not be treated with gene injections but only with cardiac electroanatomical mapping.
Study population:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 30 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •informed consent signed,
- •age between 30 and 80 years,
- •significant angina pectoris (CCS II-III) despite of maximal medication,
- •significant stenosis in coronary angiography (stenosis > 60 %),
- •contraindication to coronary angioplasty or by pass operation (diffuse or distal stenosis,
- •chronic total occlusion,
- •vessels with difficult anatomy,
- •stenosis with severe calcifications,
- •stenosis in small vessels (< 2.5 mm)),
- •reversible myocardial perfusion defects detected by pharmacological adenosine or dobutamine assisted perfusion MRI,
- •angina pectoris or ischemic ST-depression (> 1 mm) in the exercise test,
- •left ventricle wall > 8 mm detected by transthoracal echocardiography (treatment area).
排除标准
- •women in fertile age,
- •patients with type 1 diabetes mellitus or severe end-stage type 2 diabetes mellitus,
- •diabetic retinopathy,
- •atrial fibrillation,
- •clinically significant anemia (hemoglobin count < 120 mg/l in male, < 110 mg/l in female; hematocrit < 0.36), leukopenia (b-leukocyte count < 3.0x109/l), leukocytosis (b-leukocyte count > 12.0x109/l) or thrombocytopenia (b-thrombocyte count < 100x109/l), renal insufficiency (s-creatinine > 160mg/l),
- •liver insufficiency (s-alanine amino transferase and s-alcaline phosphatase over 2 x normal),
- •haematuria of unknown origin,
- •severe hypertension (systolic blood pressure > 200 mmHg or diastolic blood pressure > 110 mmHg) or significant hypotension (systolic blood pressure < 90mmHg),
- •significant obesity (BMI > 35),
- •cardiac pacemaker,
- •acute infection,
- •immunosuppressive medication,
- •significant impairment of the left ventricular function (EF < 25% in TTE or CO < 2 l in MRI),
- •congestive heart failure,
- •haemodynamically significant (gradus 3-4/4) aortic regurgitation or other heart disease needing surgery,
- •recent ( < 6 weeks) acute coronary syndrome or myocardial infarction (elevated CK-MB or cardiac troponin),
- •PCI or CABG or TIA/stroke,
- •previous or current malignancy.
研究组 & 干预措施
Gene therapy
干预措施: VEGF-D gene transfer (Biological)
Control
Control patients will have electroanatomic mapping procedure but no gene injections.
结局指标
主要结局
Assessments for safety and tolerability as measured as the acute and late adverse effects, laboratory parameters, biodistribution of the vector, anti-adenovirus antibodies and VEGF-levels before and in several time points after the gene transfer.
时间窗: 1 year
次要结局
- Efficacy of GT to increase myocardial perfusion in MRI and PET.(1 year)
- Functional capacity in exercise test, LV-function in echocardiography, arrhythmias in 24-hours Holter-recording will be analyzed.(1 year)
- Improvement in symptoms, QOL and medication.(1 year)
研究者
Juha Hartikainen
Professor, Director, Heart Center
Kuopio University Hospital