Anti-Hypertensive Agent (ACEi) and Heart Function Improvement in Association With Rho Kinase Activity Changes in Human

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2010 by National Cheng-Kung University Hospital.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
National Cheng-Kung University Hospital
ClinicalTrials.gov Identifier:
NCT01069042
First received: February 12, 2010
Last updated: February 23, 2010
Last verified: February 2010

February 12, 2010
February 23, 2010
February 2010
August 2010   (final data collection date for primary outcome measure)
The primary outcomes are the mean changes in the Rho-kinase activity in leukocytes before and after periods of treatment. [ Time Frame: 3 and 6 months ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT01069042 on ClinicalTrials.gov Archive Site
The correlation between the mean changes in Rho-kinase activity in leukocytes and cardiac function measured by echocardiography. [ Time Frame: 3 and 6 months ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
Anti-Hypertensive Agent (ACEi) and Heart Function Improvement in Association With Rho Kinase Activity Changes in Human
A Clinical Study on Anti-Hypertensive Agent (ACEi) and Heart Function Improvement

Hypothesis: Rho, one of the small GTPase proteins, and its downstream target molecule, Rho-kinase (ROCK), play important roles in mediating various cellular functions, including contractility, actin cytoskeleton organization, cell adhesion and motility, proliferation, cytokinesis and gene expressions, all of which are involved in the pathogenesis of cardiomyocyte contractility and other vascular disease. The investigators thus hypothesize that ROCK pathway plays an important role in the function and severity of heart failure (HF) and can be one of the possible pathway that currently applied cardiovascular medicine affecting their prognosis among HF treatment.

Previous study has shown that in patients with HF, intra-arterial infusion of fasudil causes preferential increase in forearm blood flow as compared with control subjects, suggesting an involvement of Rho/Rho-kinase pathway in the increased peripheral vascular HF failure remain to be examined. Besides, whether the rho kinase activity was enhanced or their response to current medication in HF patients remained unsolved.

Aim: ROCK activity and left ventricular function between HF or non-HF population survey and their response to ACEi Tx.

Study design: We will enroll subjects from clinics of National Cheng Kung University Hospital.

Subjects will be then divided to two groups by their left ventricular ejection fraction (LVEF) ratio: preserved LVEF (EF>40%) and impaired LVEF (EF<40%). All subjects will initially receive 10mg of enalapril and be gradually titrated up to 20mg with blood pressure tolerance for 6 months. Before and after 6 months, echocardiography and blood sample will be assayed for biomarkers and rho kinase activity, respectively.

Outcomes and measurement: The outcomes will include the mean changes in the Rho-kinase activity in leukocytes before and after periods of treatment. Leukocyte Rho-kinase expression and activity will be measured in cells isolated from peripheral blood samples and frozen at -80 °C. The other outcomes are the correlation between the mean changes in Rho-kinase activity in leukocytes and cardiac function measured by 2D and M-mode echocardiography. In addition, we will calculate the association of ROCK activity and B-type natriuretic peptide (BNP), high sensitivity C-reactive protein (hsCRP) as well as its relation with clinical characteristics. The demographic, relevant clinical data and laboratory results will be all collected from patients and/or medical records.

Primary Outcomes and measurement: The primary outcomes are the mean changes in the Rho-kinase activity in leukocytes before and after periods of treatment. Leukocyte Rho-kinase expression and activity will be measured in cells isolated from peripheral blood samples and frozen at -80 °C. Western Blot assays will be performed to measure Rho-kinase activity .

Secondary Outcomes and measurement: The secondary outcomes are the correlation between the mean changes in Rho-kinase activity in leukocytes and cardiac function measured by echocardiography and tissue Doppler to measure systolic and diastolic function. In addition, the association of Rho kinase activity and BNP, hsCRP as well as its relation with clinical characteristics will be measured.

Besides, we will check the renal and liver function deterioration, changes in serum potassium levels, need for kidney replacement therapy and postural hypotension or dizziness or shock events to monitor the safety issues. Other parameters of adding medication will be recorded, including side effects like cough, angioedema, skin rash, intolerance to the medication.

Interventional
Phase 4
Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Heart Failure
Drug: Enalapril
All subjects will initially receive 10mg of enalapril and be gradually titrated up to 20mg with blood pressure tolerance for 6 months.
Other Name: Renitec
  • Active Comparator: preserved LVEF under ACEi treatment
    preserved LVEF under ACEi treatment
    Intervention: Drug: Enalapril
  • Experimental: Poor LVEF group
    Poor LVEF under ACEi treatment
    Intervention: Drug: Enalapril
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
60
November 2010
August 2010   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • those subjects aged from 16 to 80 years
  • diagnosed as systolic hypertension

Exclusion Criteria:

  • renal insufficiency (serum creatinine ≥ 2.5 mg/dl)
  • hyperkalemia (serum potassium ≥ 5mmol/L)
  • with systemic inflammatory disease, including history of autoimmune disease, malignance; bilateral renal artery stenosis
  • prior intolerance of an angiotensin receptor blockade (ARB) or ACE
  • ACEi or ARB use within recent 1 month
  • record of symptomatic hypotension
Both
16 Years to 80 Years
No
Contact: Ping-Yen Liu, MD, PhD 886-6-2353535 ext 4602 larry@mail.ncku.edu.tw
Taiwan
 
NCT01069042
HR-98-096
No
Ping-Yen Liu, MD, PhD, Assistant Professor of Internal Medicine, National Cheng-Kung University Hospital
National Cheng-Kung University Hospital
Not Provided
Principal Investigator: Jyh-Hong Chen, MD, PhD National Cheng-Kung University Hospital
National Cheng-Kung University Hospital
February 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP