Clinical Trial: Influence of Testosterone Administration on Drug-Induced QT Interval Prolongation and Torsades de Pointes

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Influence of Testosterone Administration on Drug-Induced QT Interval Prolongation and Torsades de Pointes

Brief Summary: Torsades de pointes (TdP) is a potentially fatal ventricular arrhythmia associated with corrected QT (QTc) interval prolongation. More than 50 commonly used drugs available on the US market may cause QTc interval prolongation and TdP. While TdP occurs more commonly in women, 33-45% of all cases of TdP have occurred in men. Older age is a risk factor for drug-induced TdP in men, possibly due to declining serum testosterone concentrations. Available evidence shows an inverse relationship between QTc intervals and serum testosterone concentrations. In addition, experimental data, including those from the investigators' laboratory, suggest that both exogenous testosterone or progesterone administration may be protective against prolongation of ventricular repolarization and TdP. Specific Aim: Establish the influence of transdermal testosterone administration and oral progesterone administration as preventive methods by which to diminish the degree of drug-induced QT interval prolongation in men 65 years of age or older. Hypothesis: Transdermal testosterone administration and oral progesterone administration both effectively attenuate drug-induced QT interval response in older men. To test this hypothesis, transdermal testosterone, oral progesterone or placebo will be administered in a 3-way crossover study to men 65 years of age or older. QTc interval response to low-dose ibutilide will be assessed. The primary endpoints will be individually-corrected QT interval (QTcI) response to ibutilide, in the presence and absence of testosterone, and in the presence or absence of progesterone: 1) Effect on pre-ibutilide QTcI, 2) Effect on maximum post-ibutilide QTcI, 3) Effect on % change in post-ibutilide QTcI, and 2) Area under the QTcI interval-time curves.

Detailed Summary:
Sponsor: Indiana University

Current Primary Outcome:

  • Baseline (pre-ibutilide) individualized rate-corrected QT interval (QTcI) [ Time Frame: Following 7 days of testosterone, progesterone or placebo ]
    Testosterone/progesterone/placebo will be administered for 7 days - on last day, ibutilide will be administered
  • Maximum QTcI following ibutilide 0.003 mg/kg [ Time Frame: Within 8 hours following ibutilide administration ]
    Testosterone/progesterone/placebo will be administered for 7 days - on last day, ibutilide will be administered
  • Maximum % change from pretreatment value in QTcI following ibutilide 0.003 mg/kg [ Time Frame: Within 8 hours of ibutilide administration ]
    Testosterone/progesterone/placebo will be administered for 7 days - on last day, ibutilide will be administered


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Area under the QTcI versus time curve for 0-1 hour following ibutilide 0.003 mg/kg [ Time Frame: 1 hour following ibutilide administration ]
    Testosterone/progesterone/placebo will be administered for 7 days - on last day, ibutilide will be administered
  • Adverse effects associated with testosterone, progesterone and placebo [ Time Frame: During 7 day administration periods ]


Original Secondary Outcome:

  • Area under the QTcI versus time curve for 0-1 hour following ibutilide 0.003 mg/kg [ Time Frame: 1 hour following ibutilide administration ]
    Testosterone/progesterone/placebo will be administered for 7 days - on last day, ibutilide will be administered
  • Adverse effects associated with testosterone and placebo [ Time Frame: During 7 day administration periods ]


Information By: Indiana University

Dates:
Date Received: July 29, 2015
Date Started: May 2016
Date Completion: December 2018
Last Updated: February 28, 2017
Last Verified: February 2017