Phase III Randomized, Double-Blind, Placebo-Controlled Study of Dichlorphenamide for Periodic Paralyses and Associated Sodium Channel Disorders

PROTOCOL OUTLINE: This is a randomized, double-blind study. Patients are stratified by participating institution and diagnosis.

The weekly attack rate is determined during an 8-week assessment prior to therapy initiation and at crossover.

Patients are randomly assigned to oral dichlorphenamide (DCP) or placebo for 9 weeks and then cross to the alternate treatment. Patients on DCP at baseline continue on the same dose; those on acetazolamide (ACZ) at baseline receive a DCP dose equivalent to one fifth of the ACZ dose.

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

Hypokalemic periodic paralysis Typical clinical profile Normal serum thyroxine Hypokalemia during spontaneous or glucose-induced paralytic attack in subject or affected family member

Periodic paralysis associated with sodium channel 17q alpha-subunit, e.g.:

• Hyperkalemic periodic paralysis with or without myotonia
• Paramyotonia congenita with periodic paralysis

Distinct, regular episodes of weakness at least once a week and no more than 3 times a day

No history of worsening symptoms with carbonic anhydrase inhibitor

No history of life-threatening weakness episodes prior to treatment

No atypical periodic paralysis without demonstrable 17q alpha-subunit defect

--Prior/Concurrent Therapy--

No requirement for the following agents, unless for periodic paralysis:

• Diuretics
• Antiepileptics
• Antiarrhythmics
• Magnesium supplements
• Steroids
• Calcium supplements
• Beta-blockers
• Potassium supplements
• Calcium channel blockers

--Patient Characteristics--

Hepatic: No hepatic disease

Renal:

• No renal failure
• No nephrolithiasis

Cardiovascular:

• No heart disease
• No cardiac arrhythmia

Pulmonary: No restrictive or obstructive lung disease

Other:

• No active thyroid disease
• No pregnant women