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: February 17, 2014
Last verified: February 2014
  Purpose

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


Condition Intervention Phase
Periodic Paralysis
Drug: Dichlorphenamide
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Dichlorphenamide vs. Placebo for Periodic Paralysis

Resource links provided by NLM:


Further study details as provided by University of Rochester:

Primary Outcome Measures:
  • The number of attacks/week over the last 8 weeks of the initial 9-week study phase. [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Efficacy: severity-weighted attack rate; muscle strength and mass measures; changes in health-related quality-of-life; intolerable increase in attack frequency or severity necessitating withdrawal from the 9-week phase (HOP trial only). [ Time Frame: 8 to 61 weeks ] [ Designated as safety issue: No ]

Enrollment: 71
Study Start Date: June 2007
Study Completion Date: May 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Dichlorphenamide Drug: Dichlorphenamide
has been prescribed to treat periodic paralysis, but is no longer available
Placebo Comparator: Placebo
inactive substance
Drug: Placebo
an inactive substance

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 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. 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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  • Prolonged QT interval or complex ventricular ectopy between attacks
  • Distinctive physical features (2 out of 5)

    1. Low set ears
    2. Short stature
    3. Hypo-/micrognathia
    4. Clinodactyly
    5. Hypo-/hypertelorism
  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00494507

Locations
United States, California
UCLA Neurology
Los Angeles, California, United States, 90095
University of California-San Francisco
San Francisco, California, United States, 94143
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States, 66160
United States, Massachusetts
Brigham & Women's Hospital
Boston, Massachusetts, United States, 02115
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Missouri
Washington University School of Medicine
St Louis, Missouri, United States, 63110
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
University of Rochester
Rochester, New York, United States, 14642
United States, Ohio
Ohio State University
Columbus, Ohio, United States, 43210
United States, Texas
University of Texas Southwestern-Dallas
Dallas, Texas, United States, 75390
Italy
University of Milan
San Donato, Milan, Italy
United Kingdom
Institute of Neurology-Queen's Square
London, United Kingdom
Sponsors and Collaborators
University of Rochester
Investigators
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
  More Information

No publications provided

Responsible Party: Robert Griggs, MD, Principal Investigator, University of Rochester
ClinicalTrials.gov Identifier: NCT00494507     History of Changes
Other Study ID Numbers: R01NS045686-02, CRC
Study First Received: June 27, 2007
Last Updated: February 17, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Rochester:
periodic paralysis
dichlorphenamide

Additional relevant MeSH terms:
Paralyses, Familial Periodic
Hypokalemic Periodic Paralysis
Paralysis
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Metal Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
Neurologic Manifestations
Signs and Symptoms
Dichlorphenamide
Carbonic Anhydrase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 16, 2014