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

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.

• Drug: acetazolamide
• Drug: dichlorphenamide
• Drug: placebo

• Active Comparator: acetazolamide
• Active Comparator: dichlorphenamide

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