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

NCT01275352 | Withdrawn Phase 4 DMC

• 1 other identifier: CLNCKA-1
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Hypertension

Keywords

left ventricular hypertrophy; heart failure

Outcome Measures

Primary Outcomes (1)

• Change in LV mass index (g/m2) in ClC-Ka Gly/Gly83 patients and ClC-Ka Gly/Gly83 patients

  12 months

Secondary Outcomes (3)

• Change in LV relative wall thickness

  6 and 12 months

• Change in N-terminal pro-brain natriuretic peptide (NT-proBNP)

  6 and 12 months

• Change in LV mass index (g/m2)

  6 months

Study Arms (4)

Arm 1

ACTIVE COMPARATOR

Caucasian hypertensive patients who are homozygous for the ClC-Ka Gly/Gly83 allele

Drug: Eplerenone

Arm 2

ACTIVE COMPARATOR

Caucasian hypertensive patients who are homozygous for ClC-Ka Arg/Arg 83 allele

Drug: Eplerenone

Arm 3

PLACEBO COMPARATOR

Caucasian hypertensive patients who are homozygous for ClC-Ka Arg/Arg 83 allele

Drug: placebo

Arm 4

PLACEBO COMPARATOR

Caucasian hypertensive patients who are homozygous for the ClC-Ka Gly/Gly83 allele

Drug: placebo

Interventions

Eplerenone DRUG

Eplerenone 50 mg/day

Also known as: Inspra, aldosterone antagonist

Arm 1; Arm 2

placebo DRUG

placebo

Arm 3; Arm 4

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• History of heart failure with preserved or depressed ejection fraction.
• Creatinine clearance of \< 45 mL/min based on the Cockcroft-Gault formula (Appendix C).
• Pregnancy
• Life expectancy less than 12 months.
• Planned cardiac surgery or percutaneous cardiac intervention within 3 months.
• Serum potassium \>5.5 mEq/L.
• History of hyperkalemia (K\>6.0 mEq/L) with eplerenone or spironolactone.
• Myocardial infarction or stroke within 3 months of screening.
• Evidence of clinical instability (hypotension, arrhythmias, unstable angina etc.).
• Subjects on or requiring K-sparing diuretics or spironolactone.
• 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
• Known hypersensitivity to eplerenone or spironolactone.
• 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.
• Psychoses or behavioral conditions that in the opinion of the Investigator would limit study compliance.
• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• University of Pennsylvania: collaborator

Study Sites (2)

Barnes Jewish Hospital

St Louis, Missouri, 63108, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Hypertension; Hypertrophy, Left Ventricular; Heart Failure

Interventions

Eplerenone; Mineralocorticoid Receptor Antagonists

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Cardiomegaly; Heart Diseases; Hypertrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Diuretics, Potassium Sparing; Diuretics; Natriuretic Agents

Study Officials

• Thomas Cappola, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

• Gerald Dorn, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: January 10, 2011
• First Posted: January 12, 2011
• Study Start: December 1, 2011
• Primary Completion: December 1, 2014
• Study Completion: June 1, 2015
• Last Updated: June 3, 2015

Record last verified: 2015-06

Locations

US (2)