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Hyper- and Hypokalemic Periodic Paralysis Study (HYP-HOP)

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Robert Griggs, MD, University of Rochester
ClinicalTrials.gov Identifier:
NCT00494507
First received: June 27, 2007
Last updated: June 5, 2014
Last verified: June 2014

June 27, 2007
June 5, 2014
June 2007
April 2013   (final data collection date for primary outcome measure)
  • HYP Attack Rate [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.
The number of attacks/week over the last 8 weeks.
Complete list of historical versions of study NCT00494507 on ClinicalTrials.gov Archive Site
  • HYP Severity-weighted Attack Rate [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

    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.

    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 ] [ Designated as safety issue: No ]

    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.

    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 ] [ Designated as safety issue: No ]

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

    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 ] [ Designated as safety issue: No ]

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

    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).

  • HYP Change From Baseline to Week 9 in Lean Body Mass [ Time Frame: Baseline and 9 weeks ] [ Designated as safety issue: No ]
    Lean body mass was measured by dual-energy X-ray absorptiometry (DEXA).
  • HOP Change From Baseline to Week 9 in Lean Body Mass [ Time Frame: Baseline and 9 weeks ] [ Designated as safety issue: No ]
    Lean body mass was measured by dual-energy X-ray absorptiometry (DEXA).
  • HYP Change From Baseline to Week 9 in SF-36 Physical Component Summary Score [ Time Frame: Baseline and 9 weeks ] [ Designated as safety issue: No ]
    The Medical Outcomes Study Short Form (SF-36) questionnaire is a widely used profile measure of generic health-related quality of life. The 36 questions are allocated to eight scales: physical function (PF), physical role (RP), bodily pain (BP), general health perceptions (GH), vitality (VT), social function (SF), mental health (MH), and emotional role (RE). The physical component summary score is calculated from the four scales of PF, RP,BP, and GH. Higher scores are associated with better quality of life.
  • HOP Change From Baseline to Week 9 in SF-36 Physical Component Summary Score [ Time Frame: Baseline and 9 weeks ] [ Designated as safety issue: No ]
    The Medical Outcomes Study Short Form (SF-36) questionnaire is a widely used profile measure of generic health-related quality of life. The 36 questions are allocated to eight scales: physical function (PF), physical role (RP), bodily pain (BP), general health perceptions (GH), vitality (VT), social function (SF), mental health (MH), and emotional role (RE). The physical component summary score is calculated from the four scales of PF, RP,BP, and GH. Higher scores are associated with better quality of life.
  • HYP Change From Baseline to Week 9 in SF-36 Mental Health Component Summary Score [ Time Frame: Baseline and 9 weeks ] [ Designated as safety issue: No ]
    The Medical Outcomes Study Short Form (SF-36) questionnaire is a widely used profile measure of generic health-related quality of life. The 36 questions are allocated to eight scales: physical function (PF), physical role (RP), bodily pain (BP), general health perceptions (GH), vitality (VT), social function (SF), mental health (MH), and emotional role (RE). The mental health component summary score is calculated from the four scales of VT, SF, MH, and RE. Higher scores are associated with better quality of life.
  • HOP Change From Baseline to Week 9 in SF-36 Mental Health Component Summary Score [ Time Frame: Baseline and 9 weeks ] [ Designated as safety issue: No ]
    The Medical Outcomes Study Short Form (SF-36) questionnaire is a widely used profile measure of generic health-related quality of life. The 36 questions are allocated to eight scales: physical function (PF), physical role (RP), bodily pain (BP), general health perceptions (GH), vitality (VT), social function (SF), mental health (MH), and emotional role (RE). The mental health component summary score is calculated from the four scales of VT, SF, MH, and RE. Higher scores are associated with better quality of life.
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).
Not Provided
Not Provided
 
Hyper- and Hypokalemic Periodic Paralysis Study
Dichlorphenamide vs. Placebo for Periodic Paralysis

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
  • Hyperkalemic Periodic Paralysis
  • Hypokalemic Periodic Paralysis
  • Drug: Dichlorphenamide (double-blind)
    50mg tablet; maximum dosage 400mg/day
    Other Name: Daranide
  • Drug: Placebo (double-blind)
    Inactive substance manufactured to look like Dichlorphenamide 50mg tablet
  • Drug: Dichlorphenamide (open-label)
    50mg tablet; maximum dosage 400mg/day
    Other Name: Daranide
  • Active Comparator: HYP Dichlorphenamide
    Hyperkalemic participants were randomized to Dichlorphenamide for a 9 week double-blind phase. All participants then received Dichlorphenamide for a 52 week open-label phase.
    Interventions:
    • Drug: Dichlorphenamide (double-blind)
    • Drug: Dichlorphenamide (open-label)
  • Placebo Comparator: HYP Placebo
    Hyperkalemic participants were randomized to Placebo for a 9 week double-blind phase. All participants then received Dichlorphenamide for a 52 week open-label phase.
    Interventions:
    • Drug: Placebo (double-blind)
    • Drug: Dichlorphenamide (open-label)
  • Active Comparator: HOP Dichlorphenamide
    Hypokalemic participants were randomized to Dichlorphenamide for a 9 week double-blind phase. All participants then received Dichlorphenamide for a 52 week open-label phase.
    Interventions:
    • Drug: Dichlorphenamide (double-blind)
    • Drug: Dichlorphenamide (open-label)
  • Placebo Comparator: HOP Placebo
    Hypokalemic participants were randomized to Placebo for a 9 week double-blind phase. All participants then received Dichlorphenamide for a 52 week open-label phase.
    Interventions:
    • Drug: Placebo (double-blind)
    • Drug: Dichlorphenamide (open-label)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
71
May 2013
April 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Genetically definite, clinically definite or clinically probable Hyperkalemic or Hypokalemic Periodic Paralysis as outlined in the protocol
  • Male and female participants, age 18 and older who are able to comply with the study conditions.
  • Participants who have distinct regular episodes of weakness with an average frequency of > or = to 1 a week and < or = to 3 a day either on or off treatment, whichever is higher
  • Normal thyroid-stimulating hormone (TSH) level

Exclusion Criteria:

  • Evidence for Andersen-Tawil syndrome (any one of the following 3 criteria)

    1. Prolonged QT interval or complex ventricular ectopy between attacks
    2. Distinctive physical features (2 of the following 5)

      1. Low set ears
      2. Short stature
      3. Hypo-/micrognathia
      4. Clinodactyly
      5. Hypo-/hypertelorism
    3. KIR 2.1 gene mutation
  • Coincidental renal, hepatic, active thyroid disease, restrictive or obstructive lung disease, other neuromuscular disease, or heart disease
  • Chronic, non-congestive, angle-closure glaucoma
  • Use of any of the following medications for reasons other than treatment of periodic paralysis: diuretics, antiarrhythmics, corticosteroids, beta-blockers, calcium channel blockers, antiepileptics, magnesium
  • History of life-threatening episodes of respiratory muscle weakness or cardiac arrhythmias during attacks
  • Pregnancy
  • Known mutation in the alpha subunit of the sodium channel gene in hypokalemic periodic paralysis patients
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Italy,   United Kingdom
 
NCT00494507
R01NS045686-02, CRC
Yes
Robert Griggs, MD, University of Rochester
University of Rochester
National Institute of Neurological Disorders and Stroke (NINDS)
Principal Investigator: Robert C. Griggs, M.D. University of Rochester
Principal Investigator: Rabi Tawil, M.D. Co-Principal Investigator, University of Rochester
Investigator: Michael McDermott, Ph.D. Biostatistician, University of Rochester
University of Rochester
June 2014

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