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AC6 Gene Transfer for CHF

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ClinicalTrials.gov Identifier: NCT00787059
Recruitment Status : Active, not recruiting
First Posted : November 7, 2008
Last Update Posted : October 16, 2017
Sponsor:
Collaborators:
Information provided by (Responsible Party):

Study Description
Brief Summary:
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 or disease Intervention/treatment Phase
Congestive Heart Failure Drug: Ad5.hAC6 Drug: Sucrose (3%) Phase 1 Phase 2

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.

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 56 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase I/II Study AC6 Gene Transfer for Congestive Heart Failure
Study Start Date : July 2010
Primary Completion Date : January 2015
Estimated Study Completion Date : October 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Sucrose
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: Ad5.hAC6
Will receive intracoronary adenovirus encoding human adenylyl cyclase type 6
Drug: Ad5.hAC6
Intracoronary delivery of test substance in 3:1 randomization (Ad5.hAC6 : placebo) with dose escalation, starting at 3.2 x 10^9 vp to 10^12 vp in 5 dose groups
Placebo Comparator: sucrose solution
Will receive intracoronary sucrose solution
Drug: Sucrose (3%)


Outcome Measures

Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. Symptoms (KCCQ); hemodynamics; ICD discharge frequency [ Time Frame: Before, 4w, 12 w ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00787059


Locations
United States, California
University of California, San Diego
San Diego, California, United States, 92037
VA San Diego Healthcare System
San Diego, California, United States, 92161
United States, Illinois
Northwestern University Feinberg School of Medicine
Chicago, Illinois, United States, 60611
United States, Minnesota
Minneapolis Heart Institute Foundation
Minneapolis, Minnesota, United States, 55407
United States, Utah
University of Utah Health Care, Utah
Salt Lake City, Utah, United States, 84132
United States, Vermont
Fletcher Allen Health Care
Burlington, Vermont, United States, 05401
United States, Wisconsin
University of Wisconsin-Madison
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
Hammond, H. Kirk, M.D.
National Heart, Lung, and Blood Institute (NHLBI)
Renova Therapeutics
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: Jay H Traverse, MD Minneapolis Heart Institute Foundation
Principal Investigator: Clyde W Yancy, MD Bluhm Cardiovascular Institute, Northwestern Memorial Hospital
Principal Investigator: Matthew W Watkins, MD Fletcher Allen Health Care, University of Vermont
Principal Investigator: Eric D Adler, MD University of California, San Diego
Principal Investigator: David R Murray, MD University of Wisconsin, Madison
Principal Investigator: Amit Patel, MD University of Utah Health Care, Utah
More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Hammond, H. Kirk, M.D.
ClinicalTrials.gov Identifier: NCT00787059     History of Changes
Other Study ID Numbers: 365
P01HL066941 ( U.S. NIH Grant/Contract )
First Posted: November 7, 2008    Key Record Dates
Last Update Posted: October 16, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: The trial remains blinded

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
Heart Diseases
Cardiovascular Diseases