Clinical trial NCT00494507: Hyper- and Hypokalemic Periodic Paralysis Study
Official title: Dichlorphenamide vs. Placebo for Periodic Paralysis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hyperkalemic Periodic Paralysis
Hypokalemic Periodic Paralysis
Keywords: periodic paralysis
dichlorphenamide
Lead sponsor: University of Rochester
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2007-06-29
Enrollment: 71
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: HYP Attack Rate
timeFrame: 8 weeks
measure: HOP Attack Rate
timeFrame: 8 weeks
Secondary outcomes:
measure: HYP Severity-weighted Attack Rate
timeFrame: 8 weeks
measure: HOP Severity-weighted Attack Rate
timeFrame: 8 weeks
measure: HYP Attack Duration
timeFrame: 8 weeks
measure: HOP Attack Duration
timeFrame: 8 weeks
measure: HYP Endpoint of Acute Worsening
timeFrame: 0-9 weeks
measure: HOP Endpoint of Acute Worsening
timeFrame: 0-9 weeks
measure: HYP Change From Baseline to Week 9 in Average Manual Muscle Testing (MMT) Score
timeFrame: Baseline and 9 weeks
measure: HOP Change From Baseline to Week 9 in Average Manual Muscle Testing (MMT) Score
timeFrame: Baseline and 9 weeks
measure: HYP Change From Baseline to Week 9 in Average Maximum Voluntary Isometric Contraction Testing (MVICT) Scores
timeFrame: Baseline and 9 weeks
measure: HOP Change From Baseline to Week 9 in Average Maximum Voluntary Isometric Contraction Testing (MVICT) Scores
timeFrame: Baseline and 9 weeks
measure: HYP Change From Baseline to Week 9 in Average Maximum Voluntary Isometric Contraction Testing Percent of Predicted Normal
timeFrame: Baseline and 9 weeks
measure: HOP Change From Baseline to Week 9 in Average Maximum Voluntary Isometric Contraction Testing Percent of Predicted Normal
timeFrame: Baseline and 9 weeks
measure: HYP Change From Baseline to Week 9 in Lean Body Mass
timeFrame: Baseline and 9 weeks
measure: HOP Change From Baseline to Week 9 in Lean Body Mass
timeFrame: Baseline and 9 weeks
measure: HYP Change From Baseline to Week 9 in SF-36 Physical Component Summary Score
timeFrame: Baseline and 9 weeks
measure: HOP Change From Baseline to Week 9 in SF-36 Physical Component Summary Score
timeFrame: Baseline and 9 weeks
measure: HYP Change From Baseline to Week 9 in SF-36 Mental Health Component Summary Score
timeFrame: Baseline and 9 weeks
measure: HOP Change From Baseline to Week 9 in SF-36 Mental Health Component Summary Score
timeFrame: Baseline and 9 weeks
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Neurology
state: California
city: San Francisco
country: United States
facility: University of California-San Francisco
state: California
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Boston
country: United States
facility: Brigham & Women's Hospital
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Dallas
country: United States
facility: University of Texas Southwestern-Dallas
state: Texas
city: San Donato
country: Italy
facility: University of Milan
state: Milan
city: London
country: United Kingdom
facility: Institute of Neurology-Queen's Square
Study officials:
affiliation: University of Rochester
name: Robert C. Griggs, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Co-Principal Investigator, University of Rochester
name: Rabi Tawil, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Biostatistician, University of Rochester
name: Michael McDermott, Ph.D.
References: