SERCA Gene Therapy Trial
Recruitment status was Not yet recruiting
The aim of the study is to determine the safety and feasibility of giving an adeno-associated viral vector expressing the sarcoplasmic reticulum calcium ATPase (SERCA2a), driven by the CMV promoter (AAV6-CMV-SERCA2a), to heart failure patients that have received a left ventricular assist device (LVAD) for an accepted clinical indication. It is a randomised, double-blind study of 16 patients that will be randomised to receive either the study drug (AAV6.SERCA2a) or placebo.
The purpose of gene transfer of SERCA2a is to improve systolic and diastolic function of the failing ventricle. Studies show that reduction of SERCA2a in failing ventricle is a key factor in depression of contraction, and that restoration of SERCA2a levels can improve function to near normal levels. The vector will be delivered during a cardiac catheterisation procedure by a 10-minute infusion into the coronary arteries.
Myocardial tissue is obtained at the time of LVAD placement, as a routine part of device implantation. Further samples will be obtained when the heart is transplanted or the LVAD removed. Measures of tissue inflammation as well as efficacy of gene transfer will be made by comparing these two samples. Recovery of contractile function of the heart will be assessed during attempts to wean patients from the LVAD using standard protocols.
The results will be assessed in conjunction with two companion studies which will start earlier in the US, one performing SERCA2a gene transfer with the same vector, but delivered by direct injection into the myocardium during LVAD insertion, and one using AAV1-CMV-SERCA2a delivered percutaneously in heart failure patients. The latter has both a dose-ranging and placebo-controlled arm.
Advanced Heart Failure
Patients That Have Received a Left Ventricular Assist Device
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Investigation of the Safety and Feasibility of SERCA Gene Transfer in the Human Failing Heart Using an Adeno-associated Viral Vector|
- Level and extent of gene expression measured by PCR of SERCA [ Time Frame: 2 years ]
- Levels of SERCA protein
- Viral DNA and RNA
- Other relevant proteins e.g. phospholamban, the sarcoplasmic reticulum calcium release channel, the Na+/Ca2+-exchanger.
- Function of isolated myocytes (depending on availability of cardiac tissue)
- Left ventricular function assessed by echocardiography
- Incidence of major adverse cardiovascular events (MACE) at 30 days [ Time Frame: 30 days ]
|Study Start Date:||January 2010|
|Estimated Study Completion Date:||December 2012|
|Estimated Primary Completion Date:||December 2012 (Final data collection date for primary outcome measure)|
|Active Comparator: 1||
AAV6.SERCA2a will be delivered by a percutaneous method in the catheter laboratory. Dose: 5 x 10^12 DNase resistant particles
|Placebo Comparator: 2||
Saline solution delivered by same protocol as AAV6.SERCA2A, by percutaneous infusion.
|Contact: Sian Harding||0207 351 email@example.com|
|Contact: Alexander Lyon||+44 (0)207 352 8121 ext firstname.lastname@example.org|
|Papworth Hospital||Not yet recruiting|
|Cambridge, United Kingdom, CB23 3RE|
|Principal Investigator: Stephen Large|
|Principal Investigator: Steven Tsui|
|Harefield Hospital, Royal Brompton and Harefiled NHS Trust||Not yet recruiting|
|Middlesex, United Kingdom, UB9 6JH|
|Principal Investigator: Emma Birks|
|Principal Investigator:||Sian Harding||Imperial College London|