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AC6 Gene Transfer for CHF

2018年2月6日 更新者:Hammond, H. Kirk, M.D.

Phase I/II Study AC6 Gene Transfer for Congestive Heart Failure

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.

研究概览

详细说明

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.

研究类型

介入性

注册 (实际的)

56

阶段

  • 阶段2
  • 阶段1

联系人和位置

本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。

学习地点

    • California
      • San Diego、California、美国、92161
        • VA San Diego Healthcare System
      • San Diego、California、美国、92037
        • University of California, San Diego
    • Illinois
      • Chicago、Illinois、美国、60611
        • Northwestern University Feinberg School of Medicine
    • Minnesota
      • Minneapolis、Minnesota、美国、55407
        • Minneapolis Heart Institute Foundation
    • Utah
      • Salt Lake City、Utah、美国、84132
        • University of Utah Health Care, Utah
    • Vermont
      • Burlington、Vermont、美国、05401
        • Fletcher Allen Health Care
    • Wisconsin
      • Madison、Wisconsin、美国、53792
        • University of Wisconsin-Madison

参与标准

研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 至 80年 (成人、年长者)

接受健康志愿者

有资格学习的性别

全部

描述

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

学习计划

本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。

研究是如何设计的?

设计细节

  • 主要用途:治疗
  • 分配:随机化
  • 介入模型:并行分配
  • 屏蔽:四人间

武器和干预

参与者组/臂
干预/治疗
实验性的:Ad5.hAC6
Will receive intracoronary adenovirus encoding human adenylyl cyclase type 6
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
安慰剂比较:sucrose solution
Will receive intracoronary sucrose solution

研究衡量的是什么?

主要结果指标

结果测量
大体时间
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.
大体时间:Before, 4w, 12w
Before, 4w, 12w

次要结果测量

结果测量
大体时间
Symptoms (KCCQ); hemodynamics; ICD discharge frequency
大体时间:Before, 4w, 12 w
Before, 4w, 12 w

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

调查人员

  • 研究主任:H. Kirk Hammond, MD、UCSD; VA San Diego Healthcare System; Veterans Medical Research Foundation
  • 首席研究员:William Penny, MD、UCSD; VA San Diego Healthcare System; Veteran's Medical Research Foundation
  • 首席研究员:Jay H Traverse, MD、Minneapolis Heart Institute Foundation
  • 首席研究员:Clyde W Yancy, MD、Bluhm Cardiovascular Institute, Northwestern Memorial Hospital
  • 首席研究员:Matthew W Watkins, MD、Fletcher Allen Health Care, University of Vermont
  • 首席研究员:Eric D Adler, MD、University of California, San Diego
  • 首席研究员:David R Murray, MD、University of Wisconsin, Madison
  • 首席研究员:Amit Patel, MD、University of Utah Health Care, Utah

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始

2010年7月1日

初级完成 (实际的)

2015年1月1日

研究完成 (实际的)

2017年11月16日

研究注册日期

首次提交

2008年11月6日

首先提交符合 QC 标准的

2008年11月6日

首次发布 (估计)

2008年11月7日

研究记录更新

最后更新发布 (实际的)

2018年2月9日

上次提交的符合 QC 标准的更新

2018年2月6日

最后验证

2017年8月1日

更多信息

与本研究相关的术语

其他相关的 MeSH 术语

其他研究编号

  • 365
  • P01HL066941 (美国 NIH 拨款/合同)

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)?

未定

IPD 计划说明

The trial remains blinded

此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.

Ad5.hAC6的临床试验

3
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