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.
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