CLCNKA (Ka Renal Chloride Channel[ClC-Ka]) Polymorphism Effects on Hypertrophy Regression

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified August 2011 by Washington University School of Medicine
Sponsor:
Collaborator:
University of Pennsylvania
Information provided by:
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT01275352
First received: January 10, 2011
Last updated: August 2, 2011
Last verified: August 2011
  Purpose

This study will consist of middle-aged Caucasian non-failing subjects with high blood pressure who are homozygous for a gene that confers increased risk of developing heart failure, the Glycine 83 variant of the Ka renal chloride channel (ClC-Ka Gly/Gly 83), or middle-aged Caucasian non-failing hypertensive subjects who lack the heart failure risk gene, the wild-type Arginine 83 Ka renal chloride channel (ClC-Ka Arg/Arg 83). Subjects on standard therapy for high blood pressure with an angiotensin converting inhibitor (ACEI) or angiotensin receptor blocker (ARB) will be randomized to additional treatment with eplerenone (an aldosterone antagonist) or placebo, and assessed for changes in echocardiographic left ventricular hypertrophy (LVMI). Secondary endpoints will assess left ventricular remodeling and other echocardiographic variables. The investigators hypothesize that subjects homozygous for the CLCNKA risk allele will have a greater response to eplerenone in terms of reductions in LVMI than those lacking the risk allele.


Condition Intervention Phase
Hypertension
Drug: Eplerenone
Drug: placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double Blind Pilot Study Evaluating CLCNKA (Ka Renal Chloride Channel[ClC-Ka]) Polymorphism Effects on Hypertrophy Regression in Caucasian Hypertensive Patients Treated With Eplerenone

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Change in LV mass index (g/m2) in ClC-Ka Gly/Gly83 patients and ClC-Ka Gly/Gly83 patients [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in LV relative wall thickness [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]
  • Change in N-terminal pro-brain natriuretic peptide (NT-proBNP) [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]
  • Change in LV mass index (g/m2) [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 700
Study Start Date: December 2011
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm 1
Caucasian hypertensive patients who are homozygous for the ClC-Ka Gly/Gly83 allele
Drug: Eplerenone
Eplerenone 50 mg/day
Other Names:
  • Inspra
  • aldosterone antagonist
Active Comparator: Arm 2
Caucasian hypertensive patients who are homozygous for ClC-Ka Arg/Arg 83 allele
Drug: Eplerenone
Eplerenone 50 mg/day
Other Names:
  • Inspra
  • aldosterone antagonist
Placebo Comparator: Arm 3
Caucasian hypertensive patients who are homozygous for ClC-Ka Arg/Arg 83 allele
Drug: placebo
placebo
Other Name: placebo
Placebo Comparator: Arm 4
Caucasian hypertensive patients who are homozygous for the ClC-Ka Gly/Gly83 allele
Drug: placebo
placebo
Other Name: placebo

Detailed Description:

The screening phase will involve identifying Caucasian hypertensive patients who are homozygous for the ClC-Ka Gly/Gly83 and the ClC-Ka Arg/Arg 83 allele. All patients will be on background therapy with an angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) at least mid range dosing. If patient is not at recommended dose of ACE or ARB they must be titrated up and be stable on a midrange dose of ACEI or ARB for at least 4 weeks before they can be entered into the study. There will be 2 treatment phases. Phase 1 will be up to 4 weeks in duration and will consist of randomization to one table of eplerenone (25 mg) or matching placebo. On week 2 the patient will be up titrated to two tablets of eplerenone (50 mg) or matching placebo, to achieve a target dose of 50 mg of eplerenone. If the patient cannot tolerate two tablets of eplerenone or matching placebo they can be down titrated to one tablet of eplerenone or matching placebo. The target BP on study medication is < 130/80 mmHg. After the patients have been up titrated to the maximally tolerated dose of study medication, the background hypertension therapy can be adjusted to reach the target BP of < 130/80 mmHg by the end of week 4. Phase 2 will be 52 weeks in duration to assess the effects of placebo or eplerenone on LV hypertrophy. Serum potassium will be monitored throughout the study, and if necessary, doses of eplerenone will be titrated down as necessary.

  Eligibility

Ages Eligible for Study:   40 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Caucasians with hypertension who are homozygous for the ClC-Ka Gly/Gly83 and the ClC-Ka Arg/Arg 83 allele.
  2. Male or non-pregnant female aged 40 to 80 years.
  3. Hypertension, defined as currently taking high blood pressure medications or not on medications but having SDP >140 or DBP >90.
  4. Ejection fraction > 50% by any method within 6 months of the screening visit.
  5. The Investigator must obtain written informed consent before the subject is screened for the study.
  6. Subject should be on stable dose of ACE or ARB at moderate dosing for at least 4 weeks before randomization.

Exclusion Criteria:

  1. History of heart failure with preserved or depressed ejection fraction.
  2. Creatinine clearance of < 45 mL/min based on the Cockcroft-Gault formula (Appendix C).
  3. Pregnancy
  4. Life expectancy less than 12 months.
  5. Planned cardiac surgery or percutaneous cardiac intervention within 3 months.
  6. Serum potassium >5.5 mEq/L.
  7. History of hyperkalemia (K>6.0 mEq/L) with eplerenone or spironolactone.
  8. Myocardial infarction or stroke within 3 months of screening.
  9. Evidence of clinical instability (hypotension, arrhythmias, unstable angina etc.).
  10. Subjects on or requiring K-sparing diuretics or spironolactone.
  11. Concomitant use of potent inhibitors of CYP3A4 including ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, and nelfinavir or any drug noted in the Contraindications, Warnings or Precautions sections of their labeling to be potent CYP3A4 inhibitors
  12. Known hypersensitivity to eplerenone or spironolactone.
  13. Evidence of current alcohol or drug abuse Severe organic disorders or surgery or disease of the gastrointestinal tract that in the opinion of the Investigator may interfere in the absorption and elimination of the study drug.
  14. Psychoses or behavioral conditions that in the opinion of the Investigator would limit study compliance.
  15. Subjects who have received any investigational medication or used any investigational device within 30 days prior to first dose of study drug or subjects actively participating in any investigational drug or device study.
  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: NCT01275352

Contacts
Contact: Thomas Cappola, MD 215-615-0805 thomas.cappola@uphs.upenn.edu
Contact: Douglas Mann, MD 314-362-8909 dmann@dom.wustl.edu

Locations
United States, Missouri
Barnes Jewish Hospital Not yet recruiting
St. Louis, Missouri, United States, 63108
Contact: Douglas L Mann, MD    314-362-8908    dmann@dom.wustl.edu   
Contact: Angela Brown, MD    314-747-3608    abrown@dom.wustl.edu   
United States, Pennsylvania
Hospital of the University of Pennsylvania Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Thomas Cappola, MD    215-615-0805    thomas.cappola@uphs.upenn.edu   
Contact: Debbie Cohen, MD    (215) 615-0794    debbie.cohen@uphs.upenn.edu   
Sponsors and Collaborators
Washington University School of Medicine
University of Pennsylvania
Investigators
Principal Investigator: Thomas Cappola, MD University of Pennsylvania
Principal Investigator: Gerald Dorn, MD Washington University School of Medicine
  More Information

No publications provided

Responsible Party: Thomas Cappola, MD, ScM, University of Pennsylvania
ClinicalTrials.gov Identifier: NCT01275352     History of Changes
Other Study ID Numbers: CLNCKA-1
Study First Received: January 10, 2011
Last Updated: August 2, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by Washington University School of Medicine:
left ventricular hypertrophy
heart failure

Additional relevant MeSH terms:
Hypertension
Hypertrophy
Vascular Diseases
Cardiovascular Diseases
Pathological Conditions, Anatomical
Mineralocorticoid Receptor Antagonists
Eplerenone
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Diuretics, Potassium Sparing
Diuretics
Natriuretic Agents
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 15, 2014