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

January 10, 2011
August 2, 2011
December 2011
December 2015   (final data collection date for primary outcome measure)
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 ]
Same as current
Complete list of historical versions of study NCT01275352 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Change in LV relative wall thickness [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]
  • Change in 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 ]
Not Provided
Not Provided
 
CLCNKA (Ka Renal Chloride Channel[ClC-Ka]) Polymorphism Effects on Hypertrophy Regression
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

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.

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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Hypertension
  • Drug: Eplerenone
    Eplerenone 50 mg/day
    Other Names:
    • Inspra
    • aldosterone antagonist
  • Drug: placebo
    placebo
    Other Name: placebo
  • Active Comparator: Arm 1
    Caucasian hypertensive patients who are homozygous for the ClC-Ka Gly/Gly83 allele
    Intervention: Drug: Eplerenone
  • Active Comparator: Arm 2
    Caucasian hypertensive patients who are homozygous for ClC-Ka Arg/Arg 83 allele
    Intervention: Drug: Eplerenone
  • Placebo Comparator: Arm 3
    Caucasian hypertensive patients who are homozygous for ClC-Ka Arg/Arg 83 allele
    Intervention: Drug: placebo
  • Placebo Comparator: Arm 4
    Caucasian hypertensive patients who are homozygous for the ClC-Ka Gly/Gly83 allele
    Intervention: Drug: placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Not yet recruiting
700
December 2016
December 2015   (final data collection date for primary outcome measure)

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.
Both
40 Years to 80 Years
No
Contact: Thomas Cappola, MD 215-615-0805 thomas.cappola@uphs.upenn.edu
Contact: Douglas Mann, MD 314-362-8909 dmann@dom.wustl.edu
United States
 
NCT01275352
CLNCKA-1
Yes
Thomas Cappola, MD, ScM, University of Pennsylvania
Washington University School of Medicine
University of Pennsylvania
Principal Investigator: Thomas Cappola, MD University of Pennsylvania
Principal Investigator: Gerald Dorn, MD Washington University School of Medicine
Washington University School of Medicine
August 2011

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