Heart FailurePhase 4NCT01069042
Anti-Hypertensive Agent (ACEi) and Heart Function Improvement in Association With Rho Kinase Activity Changes in Human
A Phase 4 study testing Enalapril in people with Heart Failure, run by National Cheng-Kung University Hospital at 1 site in Taiwan.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 16 to 80 years
- Conditions the study is for
- Heart Failure
- What is being tested?
- Enalapril
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteTaiwan
- Study dates
- Feb 2010to Nov 2010
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 80 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- those subjects aged from 16 to 80 years
- diagnosed as systolic hypertension
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Taiwan1 site, 1 recruiting
- Recruiting
National Cheng Kung University Hospital
Tainan, Taiwan, 70401
Ping-Yen Liu, MD, PhD
About this study
Official title: 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.
Read the detailed description
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.
- Conditions
- Heart Failure
- Being tested
- Enalapril
- Keywords
- Rho kinase activity, Heart failure, ACE inhibitor, LVEF change, Rho kinase activity change
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EnalaprilDrug
Also called Renitec
All subjects will initially receive 10mg of enalapril and be gradually titrated up to 20mg with blood pressure tolerance for 6 months.
| Study group | Role | What they receive |
|---|---|---|
| preserved LVEF under ACEi treatment | Active comparator | preserved LVEF under ACEi treatment Receives: Drug: Enalapril |
| Poor LVEF group | Experimental | Poor LVEF under ACEi treatment Receives: Drug: Enalapril |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary outcomes are the mean changes in the Rho-kinase activity in leukocytes before and after periods of treatment.
Measured: 3 and 6 months
Secondary outcomes (1)
The correlation between the mean changes in Rho-kinase activity in leukocytes and cardiac function measured by echocardiography.
Measured: 3 and 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2010 (estimated)
- Study startFeb 2010
- Primary completionAug 2010 (estimated)
- Study completionNov 2010 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- More trials run by National Cheng-Kung University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cheng-Kung University Hospital
- Sponsor type
- University, hospital or other
- Investigators
- Jyh-Hong Chen, MD, PhD, Principal investigator, National Cheng-Kung University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01069042
- Sponsor's protocol ID
- HR-98-096
- Status last verified
- Feb 2010
- First submitted
- 12 Feb 2010
- Last updated
- 25 Feb 2010
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Clinical Study on Anti-Hypertensive Agent (ACEi) and Heart Function Improvement
- ClinicalTrials.gov ID
- NCT01069042
- Acronym / sponsor ID
- HR-98-096
- Conditions
- Heart Failure
- Keywords
- Rho kinase activity, Heart failure, ACE inhibitor, LVEF change, Rho kinase activity change
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- National Cheng-Kung University HospitalUniversity, hospital or other
- Study start
- Feb 2010
- Primary completion
- Aug 2010 (estimated)
- Study completion
- Nov 2010 (estimated)
- First posted
- 17 Feb 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| preserved LVEF under ACEi treatment | Active comparator | Drug: Enalaprilpreserved LVEF under ACEi treatment |
| Poor LVEF group | Experimental | Drug: EnalaprilPoor LVEF under ACEi treatment |
Who may qualify
- Ages
- 16 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- those subjects aged from 16 to 80 years
- diagnosed as systolic hypertension
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EnalaprilAlso: RenitecAll subjects will initially receive 10mg of enalapril and be gradually titrated up to 20mg with blood pressure tolerance for 6 months. | Drug | Poor LVEF group, preserved LVEF under ACEi treatment |
Primary outcome
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
1 secondary outcome
The correlation between the mean changes in Rho-kinase activity in leukocytes and cardiac function measured by echocardiography.
Time frame: 3 and 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2010.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jyh-Hong Chen, MD, PhD principal investigator
National Cheng-Kung University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Enalapril in people with Heart Failure, run by National Cheng-Kung University Hospital at 1 site in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 25 Feb 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ping-Yen Liu, MD, PhD (886-6-2353535 ext. 4602, larry@mail.ncku.edu.tw), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Feb 2010.