AC6 Gene Transfer for CHF

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2013 by Hammond, H. Kirk, M.D.
Sponsor:
Collaborators:
Renova Therapeutics Incorporated
Information provided by (Responsible Party):
Hammond, H. Kirk, M.D.
ClinicalTrials.gov Identifier:
NCT00787059
First received: November 6, 2008
Last updated: July 17, 2013
Last verified: July 2013
  Purpose

This research study is designed to determine: 1) whether gene transfer using an agent called Ad5.hAC6 (adenovirus-5 encoding human adenylyl cyclase type 6) can be given safely to patients with congestive heart failure (CHF) and 2) whether this agent may be of benefit in heart failure. Gene transfer is a process by which genes are introduced into cells and the cells then produce the specific protein that the gene directs, in this case, a protein known as adenylyl cyclase type 6 (AC6). The gene is carried into the heart cells by a modified virus. The virus that is modified is an adenovirus (Ad5), a virus that sometimes causes a brief cold. In extensive animal experiments, it was found that increased amounts of AC6 protein in heart cells appeared to make the heart pump more vigorously.


Condition Intervention Phase
Congestive Heart Failure
Drug: Ad5.hAC6
Drug: Sucrose (3%)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase I/II Study AC6 Gene Transfer for Congestive Heart Failure

Resource links provided by NLM:


Further study details as provided by Hammond, H. Kirk, M.D.:

Primary Outcome Measures:
  • Combined: a) Exercise treadmill time; b) LV function by echocardiography before and during dobutamine infusion; c) Rate of LV pressure development and decline (dP/dt and -dP/dt) before and during dobutamine infusion. [ Time Frame: Before, 4w, 12w ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Symptoms (KCCQ); hemodynamics; ICD discharge frequency [ Time Frame: Before, 4w, 12 w ] [ Designated as safety issue: No ]

Estimated Enrollment: 56
Study Start Date: July 2010
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ad5.hAC6
Will receive intracoronary adenovirus encoding human adenylyl cyclase type 6
Drug: Ad5.hAC6
Intracoronary delivery of Ad5.hAC6 or sucrose solution (placebo) in 3:1 randomization (Ad5.hAC6 : placebo) with dose escalation, starting at 3.2 x 10^9 vp to 3.2x10" vp in 5 dose groups
Placebo Comparator: sucrose solution
Will receive intracoronary sucrose solution
Drug: Sucrose (3%)

Detailed Description:

This research study is designed to determine: 1) whether gene transfer using an agent called Ad5.hAC6 (adenovirus-5 encoding human adenylyl cyclase type 6) can be given safely to patients with congestive heart failure (CHF) and 2) whether this agent may be of benefit in heart failure. Gene transfer is a process by which genes are introduced into cells and the cells then produce the specific protein that the gene directs, in this case, a protein known as adenylyl cyclase type 6 (AC6). The gene is carried into the heart cells by a modified virus. The virus that is modified is an adenovirus (Ad5), a virus that sometimes causes a brief cold. In extensive animal experiments, it was found that increased amounts of AC6 protein in heart cells appear to make the heart pump more vigorously.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  1. Male or non-pregnant female patients aged 18-80 years of age
  2. ≥3-month history of heart failure
  3. Compensated (stable) CHF not on intravenous inotropes, vasodilators or diuretics, on optimal medical and device therapy as defined by AHA/ACC Guidelines
  4. LV ejection fraction (on optimal therapy) no greater than 40%
  5. Implanted cardiac defibrillator
  6. At least one major coronary artery (or graft) with <50% proximal obstruction
  7. Patients unable to walk (spinal injury, orthopedic problems) can be enrolled if all other criteria are met.
  8. Women of child-bearing capacity must have a negative pregnancy test within 2 days of test substance administration, and female and male patients must be willing to use birth control during sex for 12w after test substance administration if the female partner is of child-bearing capacity.
  9. Subjects willingly provide informed consent consistent with ICH-GCP guidelines

Exclusion Criteria

  1. Unstable or Class IV angina
  2. Coronary revascularization planned or predicted in next 6 months
  3. Ischemic myocardium in 3 or more regions of a single perfusion bed, as assessed by stress echocardiography or jeopardized viable myocardium >15% on perfusion imaging.
  4. ≥50% occlusion of an "unprotected" left main coronary artery. If arterial or venous conduits provide blood flow to the distal left coronary circulation (ie, patent bypass grafts) then left main disease is "protected" and such patients are not excluded. The cardiologist performing the cardiac catheterization will make these decisions.
  5. 2° AV Block (Mobitz 2) or 3° AV block unless pacemaker is present
  6. Hospitalization for CHF requiring intravenous inotropes or vasodilators in the past 4 weeks
  7. History of biopsy proven myocarditis
  8. Myocardial infarction in previous 6 months
  9. Restrictive, hypertrophic or infiltrative cardiomyopathy or chronic pericarditis
  10. Previous or planned organ transplant recipient or donor.
  11. Thrombocytopenia (<100,000 platelets/µl) or bleeding diathesis
  12. COPD requiring supplemental oxygen at home
  13. AST > 2 times upper limit of normal or chronic liver disease such as cirrhosis or Hepatitis C Virus (HCV). Patients with HCV are eligible only if both of two conditions are met: a) liver function tests are normal; AND b) liver biopsy is normal or shows only mild fibrosis.
  14. Current or predicted hemodialysis within 12 months or estimated glomerular filtration rate (EGFR) <30 ml/min. On online EGFR calculator that uses sex, age, body weight and serum creatinine is available at: www.kidney.org/professionals/kdoqi/gfr_calculator.cfm. Use the higher of two EGFR results, which are based upon MDRD and CKD-EPI formulas.
  15. CVA or TIA <6 months prior to enrollment
  16. Patients who are immunosuppressed by medicines (corticosteroids, methotrexate, cyclophosphamide, cyclosporine), illnesses (AIDS, HIV), or neutrophil count <1000/mm3
  17. Patients receiving other investigational drug therapy within 30 days of enrollment including gene transfer
  18. Patients with diseases other than CHF that, in the opinion of the investigator, put the subject at risk or adversely affect the results
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00787059

Contacts
Contact: H. Kirk Hammond, MD 858-642-3542 khammond@ucsd.edu
Contact: Eileen M D'Souza 858-642-3542 edsouza@vapop.ucsd.edu

Locations
United States, California
VA San Diego Healthcare System Recruiting
San Diego, California, United States, 92161
Contact: William Penny, MD    858-642-1129    wpenny@ucsd.edu   
Contact: Tiffany M Hancock    858-642-1129    tiffany.hancock@va.gov   
Sub-Investigator: Alan Maisel, MD         
Sub-Investigator: Denise Barnard, MD         
Sub-Investigator: Dan Blanchard, MD         
Sub-Investigator: Robert S Ross, MD         
United States, Illinois
Northwestern University Feinberg School of Medicine Recruiting
Chicago, Illinois, United States, 60611
Contact: Clyde W Yancy, MD    312-926-2492    cyancy@nmff.org   
Contact: Daniel Roshevsky, CCRC    312-695-3264    droshevs@nmh.org   
Principal Investigator: Clyde W Yancy, MD         
Sub-Investigator: Ranya Sweis, MD         
Sub-Investigator: Keith Benzuly, MD         
Sub-Investigator: James Flaherty, MD         
Sub-Investigator: Robert Gordon, MD         
United States, Minnesota
Minneapolis Heart Institute Foundation Recruiting
Minneapolis, Minnesota, United States, 55407
Contact: Timothy D Henry, MD    612-863-7372    henry003@umn.edu   
Contact: Rachel Olson,, RN,MS,MBA,CCRC    612-863-3818    rachel.olson@allina.com   
Principal Investigator: Timothy D Henry, MD         
United States, Vermont
Fletcher Allen Health Care Recruiting
Burlington, Vermont, United States, 05401
Contact: Matthew W Watkins, MD    802-847-3734    matthew.watkins@vtmednet.org   
Contact: Linda Chadwick, RN    802-847-4744    linda.chadwick@vtmednet.org   
Principal Investigator: Matthew W Watkins, MD         
Sub-Investigator: Martin M LeWinter, MD         
Sub-Investigator: Peter C VanBuren, MD         
Sub-Investigator: David J Coyle, MD         
Sub-Investigator: Enkhtuyaa L Mueller, MD         
Sub-Investigator: Cameron W Donaldson, MD         
Sub-Investigator: Magdalena A Zeglin-Sawczuk, MD         
Sponsors and Collaborators
Hammond, H. Kirk, M.D.
Renova Therapeutics Incorporated
Investigators
Study Director: H. Kirk Hammond, MD UCSD; VA San Diego Healthcare System; Veterans Medical Research Foundation
Principal Investigator: William Penny, MD UCSD; VA San Diego Healthcare System; Veteran's Medical Research Foundation
Principal Investigator: Timothy D Henry, MD Minneapolis Heart Institute Foundation
Principal Investigator: Clyde W Yancy, MD Bluhm Cardiovascular Institute, Northwestern Memorial Hospital
Principal Investigator: Matthew Watkins, MD Fletcher Allen Health Care, University of Vermont
  More Information

No publications provided

Responsible Party: Hammond, H. Kirk, M.D.
ClinicalTrials.gov Identifier: NCT00787059     History of Changes
Other Study ID Numbers: 365, P01HL066941
Study First Received: November 6, 2008
Last Updated: July 17, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Hammond, H. Kirk, M.D.:
Adenylyl Cyclase
AC6
adenovirus
gene therapy
congestive heart failure
intracoronary
nitroprusside

Additional relevant MeSH terms:
Heart Failure
Cardiovascular Diseases
Heart Diseases

ClinicalTrials.gov processed this record on October 22, 2014