Clinical Trial: Hyper- and Hypokalemic Periodic Paralysis Study

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Dichlorphenamide vs. Placebo for Periodic Paralysis

Brief Summary: The purpose of this study is to compare Dichlorphenamide with placebo (an inactive substance) for prevention of episodes and for improvement of strength in hyperkalemic (HYP) and hypokalemic (HOP) periodic paralysis. This study will also look at the long-term effects of Dichlorphenamide in periodic paralysis.

Detailed Summary:

Periodic paralysis is a relatively rare, life-long disorder characterized by intermittent bouts of paralysis, progressive weakness, and diminished quality of life. Two drugs, acetazolamide (ACZ) and dichlorphenamide, have been prescribed to treat the disorder, however, dichlorphenamide is no longer available.

In this multi-center, parallel, randomized trial researchers will compare the effects of dichlorphenamide vs. placebo in patients with hyperkalemic (HYP) and hypokalemic (HOP) periodic paralysis.

The trial consists of two 9-week studies—one study will enroll persons with hyperkalemic periodic paralysis and the other study will enroll persons with hypokalemic periodic paralysis. Participants will be randomly assigned to one of two treatment groups: dichlorphenamide or placebo (an inactive substance). During the studies, participants will be asked to keep a daily diary to record the time, length, and severity of each episode of weakness (attack). The study coordinator will contact participants weekly to review the diary information.

The 9-week phase will be followed by a 1-year open-label dichlorphenamide extension without placebo to determine the long-term effects of dichlorphenamide on the course of the disease and on inter-attack weakness.

Duration of the trial for participants is approximately 65 weeks, including a screening phase to determine eligibility, the first 9-week treatment phase, and the one-year open-label extension phase.


Sponsor: University of Rochester

Current Primary Outcome:

  • HYP Attack Rate [ Time Frame: 8 weeks ]
    The number of distinct attacks per week over the final 8 weeks (Weeks 2-9) of the double-blind treatment period as self-reported by HYP participants.
  • HOP Attack Rate [ Time Frame: 8 weeks ]
    The number of distinct attacks per week over the final 8 weeks (Weeks 2-9) of the double-blind treatment period as self-reported by HOP participants.


Original Primary Outcome: The number of attacks/week over the last 8 weeks.

Current Secondary Outcome:

  • HYP Severity-weighted Attack Rate [ Time Frame: 8 weeks ]
    HYP participant severity-weighted attack rate is defined as the sum of average attack severity across all distinct attacks over the final 8 weeks (Weeks 2-9) of the double-blind treatment period divided by the number of weeks that the subject was followed. Attack severity (scored as 1-10 with increasing severity) is self-reported.
  • HOP Severity-weighted Attack Rate [ Time Frame: 8 weeks ]
    HOP participant severity-weighted attack rate is defined as the sum of average attack severity across all distinct attacks over the final 8 weeks (Weeks 2-9) of the double-blind treatment period divided by the number of weeks that the subject was followed. Attack severity (scored as 1-10 with increasing severity) is self-reported.
  • HYP Attack Duration [ Time Frame: 8 weeks ]
    HYP participant total attack duration per week, defined as the sum of attack durations across all distinct attacks over the final 8 weeks (Weeks 2-9) of the double-blind treatment period divided by the number of weeks that the subject was followed.
  • HOP Attack Duration [ Time Frame: 8 weeks ]
    HOP participant total attack duration per week, defined as the sum of attack durations across all distinct attacks over the final 8 weeks (Weeks 2-9) of the double-blind treatment period divided by the number of weeks that the subject was followed.
  • HYP Endpoint of Acute Worsening [ Time Frame: 0-9 weeks ]
    Increase in attack frequency or severity in HYP participants necessitating withdrawal from the initial nine-week double-blind treatment period and moving directly into the open-label phase.
  • HOP Endpoint of Acute Worsening [ Time Frame: 0-9 weeks ]
    Increase in attack frequency or severity in HOP participants necessitating withdrawal from the initial nine-week double-blind treatment period and moving directly into the open-label phase.
  • HYP Change From Baseline to Week 9 in Average Manual Muscle Testing (MMT) Score [ Time Frame: Baseline and 9 weeks ]

    The strength of each of 26 individual muscles was graded using a modified 13-point Medical Research Council scale ranging from 0-5. Recorded grades were converted to numerical values as follows prior to averaging across muscles to form a composite score: 0 = 0; 1 = 1; 2- = 1.67; 2 = 2; 2+ = 2.33; 3- = 2.67; 3 = 3; 3+ = 3.33; 4- = 3.67; 4 = 4; 4+ = 4.33; 5- = 4.67; 5 = 5. A higher score represents a better outcome, i.e. 5 = normal strength.

    The following muscles were tested: shoulder abductor (left/right), elbow extensor (left/right), elbow flexor (left/right), wrist extensor (left/right), wrist flexor (left/right), hip flexor (left/right), hip extensor (left/right), hip abductor (left/right), knee extensor (left/right), knee flexor (left/right), ankle dorsiflexor (left/right), ankle plantar flexor (left/right), neck extensor, neck flexor.

  • HOP Change From Baseline to Week 9 in Average Manual Muscle Testing (MMT) Score [ Time Frame: Baseline and 9 weeks ]

    The strength of each of 26 individual muscles was graded using a modified 13-point Medical Research Council scale ranging from 0-5. Recorded grades were converted to numerical values as follows prior to averaging across muscles to form a composite score: 0 = 0; 1 = 1; 2- = 1.67; 2 = 2; 2+ = 2.33; 3- = 2.67; 3 = 3; 3+ = 3.33; 4- = 3.67; 4 = 4; 4+ = 4.33; 5- = 4.67; 5 = 5. A higher score represents a better outcome, i.e. 5 = normal strength.

    The following muscles were tested: shoulder abductor (left/right), elbow extensor (left/right), elbow flexor (left/right), wrist extensor (left/right), wrist flexor (left/right), hip flexor (left/right), hip extensor (left/right), hip abductor (left/right), knee extensor (left/right), knee flexor (left/right), ankle dorsiflexor (left/right), ankle plantar flexor (left/right), neck extensor, neck flexor.

  • HYP Change From Baseline to Week 9 in Average Maximum Voluntary Isometric Contraction Testing (MVICT) Scores [ Time Frame: Baseline and 9 weeks ]

    The strength of each of 10 muscles was measured using quantitative myometry and expressed as the number of standard deviations from normal (Z-score) given the participant's age, gender, and height. The scores were averaged across muscles to form a composite MVICT score: average standardized MVICT score. A positive Z-score indicates a better outcome.

    The following muscles were tested: elbow extensor (left/right), elbow flexor (left/right), knee extensor (left/right), knee flexor (left/right), and hand grip (left/right).

  • HOP Change From Baseline to Week 9 in Average Maximum Voluntary Isometric Contraction Testing (MVICT) Scores [ Time Frame: Baseline and 9 weeks ]


    Original Secondary Outcome: Efficacy: severity-weighted attack rate; muscle strength and mass measures; intolerable increase in attack frequency or severity necessitating withdrawal from the treatment period (HOP trial only).

    Information By: University of Rochester

    Dates:
    Date Received: June 27, 2007
    Date Started: June 2007
    Date Completion:
    Last Updated: April 4, 2017
    Last Verified: April 2017