Document Detail

Phase I clinical trial on intracoronary administration of Ad-hHGF treating severe coronary artery disease.
MedLine Citation:
PMID:  18649012     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Therapeutic angiogenesis is a new strategy for treatment of vascular insufficiency. Hepatocyte growth factor (HGF)-induced angiogenesis has been applied to induce the neovascularization of ischemic adult tissues in preclinical studies. This report summarizes a phase I clinical trial on the safety of adenovirus-mediated human HGF (Ad-HGF) gene transfer to treat clinically significant coronary artery disease. METHODS: The 18 patients with severe and diffused triple vessel disease determined by coronary angiography, 1-3 of the main coronary arteries not amenable to bypassing grafting and to catheter-based revascularization were assigned to 3 study groups according to the dose of Ad-HGF (from low to high), and the total dose as follows: 5 x 10(9) pfu (group A, n = 6); 1 x 10(10) pfu (group B, n = 6); 2 x 10(10) pfu (group C, n = 6). Arterial gene transfer was performed by over-the wire balloon to the distal of the accessible artery or otherwise the ostium of the target vessels by diagnostic coronary catheter. General safety parameters and cardiac-specific parameters were measured through the preoperative period and on day 7, 21, and 35 postoperatively. The safety and tolerance of Ad-HGF for patients were evaluated according to functional and cytological assessments. RESULTS: During the acute phase up to day 35 and at 11-14 months of follow-up there were no serious adverse events. A mild fever during the first 3 days was not present at day 4, and no long term or paroxysmal fever was found. There were no acute alterations in hemodynamic parameters and the electrocardiogram remained normal. No serious pericardial effusion was reported and there were no arrhythmia on Holter registrations. Moreover, the serum levels of HGF were not changed and the serum anti-adenovirus in the patients was not detected up to day 35. CONCLUSIONS: The present study demonstrates that it is feasible to safely use an adenovirus gene-transfer vector to deliver the human hepatocyte growth factor gene to individuals with clinically significant coronary artery disease by direct intracoronary injection. However, a great deal of additional work must be done before administration of Ad-HGF can be recommended for clinical practice.
Zhi-Jian Yang; You-Rong Zhang; Bo Chen; Shu-Lan Zhang; En-Zhi Jia; Lian-Sheng Wang; Tie-Bing Zhu; Chun-Jian Li; Hui Wang; Jun Huang; Ke-Jiang Cao; Wen-Zhu Ma; Bin Wu; Li-Sheng Wang; Chu-Tse Wu
Publication Detail:
Type:  Clinical Trial, Phase I; Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-07-22
Journal Detail:
Title:  Molecular biology reports     Volume:  36     ISSN:  1573-4978     ISO Abbreviation:  Mol. Biol. Rep.     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-05-27     Completed Date:  2009-08-17     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0403234     Medline TA:  Mol Biol Rep     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1323-9     Citation Subset:  IM    
Department of Cardiovascular Medicine, The First Affiliated Hospital of Nanjing Medical University, Guangzhou Road 300, Nanjing, 210029, Jiangsu Province, People's Republic of China.
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MeSH Terms
Aged, 80 and over
Coronary Disease / complications,  therapy*
Dose-Response Relationship, Drug
Gene Therapy / adverse effects,  methods*
Hepatocyte Growth Factor / administration & dosage*
Middle Aged
Neovascularization, Physiologic / drug effects
Treatment Outcome
Reg. No./Substance:
67256-21-7/Hepatocyte Growth Factor

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