Hyper- and Hypokalemic Periodic Paralysis Study

Condition(s) targeted: Paralysis, Periodic

Intervention: acetazolamide (Drug); dichlorphenamide (Drug); placebo (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: University of Rochester

Official(s) and/or principal investigator(s):
Robert C. Griggs, M.D., Principal Investigator
Rabi Tawil, M.D., Affiliation: Co-Principal Investigator
Michael McDermott, Ph.D., Affiliation: Biostatistician

Overall contact:
Patty Smith, Phone: 585-275-4339

The purpose of this study is to determine which drug, acetazolamide or dichlorphenamide is better for treating periodic paralysis and for improving strength.

Official title: Dichlorphenamide vs. Acetazolamide for Periodic Paralysis

Study design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Efficacy Study

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

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).

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. And, it is not known which drug better prevents episodes of paralysis or the chronic, progressive weakness that occurs between episodes. Also, unknown is which drug is preferable for preventing episodes and treating weakness.

In this multi-center, parallel, randomized trial researchers will compare acetazolamide and dichlorphenamide to determine which is better for preventing episodes of paralysis, treating weakness, and improving strength.

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 three treatment groups: acetazolamide, dichlorphenamide, or placebo (an inactive substance). During the studies, participants will be asked to keep a daily computer 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 studies will be followed by 1-year extensions to compare the long-term effects of acetazolamide and dichlorphenamide on the course of periodic paralysis. Participants who initially received a placebo during the 9-week studies will be randomly assigned to receive either acetazolamide or dichlorphenamide during the extension studies.

Duration of the trial for participants is a maximum of 61 weeks, including the first 9-week treatment phase and the one-year extension phase.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Genetically definite, clinically definite or clinically probable HYP or HOP 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 >1 a week and <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 out of 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, respiratory, other neuromuscular disease, or heart

disease

- 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 (prior to treatment)

- Pregnancy

- Allergy to sulfonamides

Patty Smith, Phone: 585-275-4339

Hospital Pitie-Salpetriere, Salpetriere, Paris, France; Not yet recruiting
Savine Vicart, Phone: 33 140 778119
Bertrand Fontaine, MD, Principal Investigator

Institute of Neurology-Queen's Square, London, United Kingdom; Not yet recruiting
Susan Tomlinson, Phone: 011 44 207 837 3611, Ext: 4251
Michael Hanna, MD, Principal Investigator

University of California-San Francisco, San Francisco, California 94143, United States; Recruiting
Kristin Wong, Phone: 415-502-3976
Jeffrey Ralph, MD, Principal Investigator

University of Kansas Medical Center, Kansas City, Kansas 66160, United States; Recruiting
Maureen Walsh, Phone: 913-588-5095
Richard Barohn, MD, Principal Investigator

Brigham & Women's Hospital, Boston, Massachusetts 02115, United States; Recruiting
Kristen Whiteside, Phone: 617-525-6763
Anthony Amato, MD, Principal Investigator

University of Milan, San Donato, Milan, Italy; Not yet recruiting
Valeria Sansone, Phone: 39 02 5607450
Giovanni Meola, MD, Principal Investigator

Mayo Clinic, Rochester, Minnesota 55905, United States; Recruiting
Janet Fisher, Phone: 507-538-2433
Brian Crum, MD, Principal Investigator

University of Rochester, Rochester, New York 14642, United States; Recruiting
Patty Smith, Phone: 585-275-4339
Emma Ciafaloni, MD, Principal Investigator

Columbia University Medical Center, New York, New York 10032, United States; Recruiting
Kate Bednarz, Phone: 212-305-2027
Petra Kaufmann, MD, Principal Investigator

Ohio State University, Columbus, Ohio 43210, United States; Recruiting
Amy Bartlett, Phone: 614-366-9050
John Kissel, MD, Principal Investigator

London Health Sciences Center, London, Ontario N6A 5A5, Canada; Not yet recruiting
Wilma Koopman, Phone: 519 663-3041
Angelika Hahn, MD, Principal Investigator

University of Texas Southwestern-Dallas, Dallas, Texas 75390, United States; Recruiting
Nina Gorham, Phone: 214-648-0462
Stephen C. Cannon, MD, Principal Investigator

Starting date: June 2007
Ending date: November 2010
Last updated: July 29, 2008