Phase I clinical trial on intracoronary administration of Ad-hHGF treating severe coronary artery disease

Yang, Zhaohui; Zhang, Yourong; Chen, Bin; Zhang, Shulan; Jia, En-Zhi; Wang, Liansheng; Zhu, Tongyu; Li, Chunjian; Wang, Hui; Huang, Jun; Cao, Kejiang; Ma, Wei; Wu, Bin; Wang, Lisheng; Wu, Chu-Tse

doi:10.1007/s11033-008-9315-3

Cited by 60 publications

(35 citation statements)

References 22 publications

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“…In several ischemia animal models, Ad-HGF gene transfer proved to have efficient angiogenesis effects without apparent toxicity and mutation [7,8]. Our preceding phase I clinical study demonstrated the shortterm safety of direct intracoronary administration of Ad-HGF to treat severe coronary disease, which showed that in the acute phase, up to day 35, there were no serious adverse events [9]. This study is a longterm follow-up of our prior phase I clinical trial.…”

Section: Introductionmentioning

confidence: 63%

“…The written consents were obtained from all patients. Each patient received the optimal standardized medication therapy for coronary disease including aspirin or clopidogrel, beta blockers, statins, angiotensin conversion enzyme inhibitors or angiotensin II receptor blockers, and was treated with Ad-HGF only once (constructed and produced by Chinese Academy of Military Medical Sciences) [9][10][11][12]. Inclusion criteria for the intracoronary gene transfer were 50-80 years old with Canadian Cardiovascular Society class II to III angina, suffered from diffused and severe coronary disease confirmed by coronary angiography, the main coronaries not amenable to interventional therapy (angioplasty or stenting) or bypassing grafting, and no emergency revascularization during follow-ups.…”

Section: Methodsmentioning

confidence: 99%

“…Based on the previous study [9,10], Ad-HGF gene was transferred to the distal part of the accessible artery by over-the wire balloon. If the vessel could not be reached, the procedure was performed by diagnostic coronary catheter at the ostium of the target vessels [9,10]. Ad-HGF was diluted to 2 ml with normal saline and then injected within 30 sec, followed by flushing of the catheter with normal saline.…”

Section: Gene Transfermentioning

confidence: 99%

“…Ad-HGF was diluted to 2 ml with normal saline and then injected within 30 sec, followed by flushing of the catheter with normal saline. Coronary angiograms were obtained at the end of each infusion [9,10].…”

Section: Gene Transfermentioning

confidence: 99%

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Safety and Efficacy of Intracoronary Ad-HGF Administration for Treating Severe Coronary Disease: Results From Long-Term Follow-Up of a Phase I Clinical Trial

Meng¹,

Du²,

Chen³

et al. 2017

J Clin Trial

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Objective: This study is a long-term follow-up of our previous phase I clinical trial and aims at evaluating the long-term safety and efficacy of intracoronary Ad-HGF administration for treating coronary disease.Methods: This study includes 22 patients (11 in the experiment group and 11 in the control group) with diffused and severe coronary disease who had received the optimal standardized medication therapy and was not amenable to revascularization. Intracoronary Ad-HGF gene transfer was administered to the distal part of the accessible artery by over-the wire balloon or at the ostium of the target vessels by diagnostic coronary catheter in the experiment group. Safety parameters were measured and compared between baseline and follow-ups (5-week; 12-month; 36-month) only in the experiment group. The changes of efficacy parameters (ejection fraction, EF) from baseline to 36-month follow-up (δEF) were measured in both groups and compared with each other. Results:This study confirmed the long-term safety of intracoronary Ad-HGF administration for treating severe diffuse coronary disease. All the eleven patients of the experiment group were alive after 36-months follow-up. During the follow-up, no new-onset arrhythmia was recorded; no malignant tumor was diagnosed; no paroxysmal or long-term fever was recorded; no retinal vascular anomaly was diagnosed. There were no statistically significant differences between the follow-ups and baseline in regard to blood parameters, including WBC, Hb, ALT, AST, BUN, Cr, CEA and AFP. In addition, intracoronary Ad-HGF efficiently improved echocardiographic EF at the 36-month follow-up compared to baseline (F=4.4, p=0.024) and with the control group (δEF: 3.5 ± 1.1 vs. -4.5 ± 1.3, MD: 8, p=0.0001). The medium-high dose subgroup also showed higher ECT-EF at the 36-month follow-up than baseline (MD: 4.8, p=0.017, n=8) and higher improvement of ECT-EF than the control group (δEF: 4.8 ± 1.5 vs. 0.3 ± 1.7, MD: 4.5, p=0.08). Conclusion:Intracoronary Ad-HGF administration is safe and potentially efficient in improving EF of patients with severe diffuse coronary disease in 3-year follow-up.

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Section: Introductionmentioning

confidence: 63%

Section: Methodsmentioning

confidence: 99%

Section: Gene Transfermentioning

confidence: 99%

Section: Gene Transfermentioning

confidence: 99%

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Safety and Efficacy of Intracoronary Ad-HGF Administration for Treating Severe Coronary Disease: Results From Long-Term Follow-Up of a Phase I Clinical Trial

Meng¹,

Du²,

Chen³

et al. 2017

J Clin Trial

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“…Different routes of administration and viral vectors have been tested in small and large animal models with encouraging results [87,88]. Preliminary clinical trials have been conducted for delivering AAV1-SERCA2 [89] or AD-HGF [90] through intracoronary infusion, and have reported benefits in patients with severe heart failure.…”

Section: Regeneration Of Myocardiummentioning

confidence: 99%

Looking Beyond Reperfusion

2016

JCCR

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Acute Myocardial Infarction is thrombotic occlusion of coronary artery and sudden stoppage of blood supply leading to death of heart muscles. The Reperfusion phase of the treatment although promising could salvage at best only 2-4% of the myocardium at 6 months and also carries the risk of reperfusion injury. Despite the best optimal reperfusion therapy, the mortality of AMI still remains 9% at one year and cardiac failure occurs in 11.0%. This appeals us to look beyond reperfusion therapy, repairing or regenerating lost myocardium via cell based therapy, tissue engineering and gene therapy. Efforts are directed towards regenerating myocardium which may revolutionize the treatment of AMI. This not only will decrease the mortality but also improve long term survival and quality of life.

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Gene therapy in cardiovascular diseases: A review of recent updates

Gorabi

Hajighasemi

Tafti

et al. 2018

J of Cellular Biochemistry

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Gene therapy is considered as a promising approach for treating cardiac dysfunction. In this review, we evaluated the clinical trials assessing gene therapy in cardiovascular diseases (CVD) from 2000 to 2017. PubMed and ClinicalTrials.gov (only English language) were searched for clinical trials published between January 2000 and May 2017, using the search terms "gene transfer" OR "gene therapy" and "cardiovascular diseases" and related terms. The trials with sample size lower than 10 patients were excluded. Twenty-six clinical trials on human and animals, including 1543 patients were listed and evaluated. The sample size in 14 trials was lower than 100 patients and in seven trials lower than 20 patients. Eleven trials used plasmid DNA and eight trials used adenovirus, one study used plasmid DNA, adenovirus, and liposome. We detected that gene therapy was a safe approach and improved the symptoms of CVD; however, the effect of gene therapy on the cardiac dysfunction is controversial.

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Phase I clinical trial on intracoronary administration of Ad-hHGF treating severe coronary artery disease

Cited by 60 publications

References 22 publications

Safety and Efficacy of Intracoronary Ad-HGF Administration for Treating Severe Coronary Disease: Results From Long-Term Follow-Up of a Phase I Clinical Trial

Safety and Efficacy of Intracoronary Ad-HGF Administration for Treating Severe Coronary Disease: Results From Long-Term Follow-Up of a Phase I Clinical Trial

Looking Beyond Reperfusion

Gene therapy in cardiovascular diseases: A review of recent updates

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