bumetanide in hypokalaemic periodic paralysis

Conditions: Hypokalemic Periodic Paralysis

Summary: this is a randomised, double-blind, placebo-controlled phase ii clinical trial with a cross-over design to investigate the efficacy of bumetanide in patients with hypokalemic periodic paralysis (hypopp). the aim is to assess the efficacy of bumetanide in reducing severity and duration of a focal attack of weakness in a hand muscle. twelve participants will be recruited.

interested patients who provisionally meet inclusion/exclusion criteria will attend nhnn for a screening visit to check study eligibility and to have any questions relating to study participation answered. each patient will undertake two assessment visits at approximately four weeks apart. study participants will withhold carbonic anhydrase inhibitor medications for 72 hours prior to assessment visits as is standard for mcmanis testing and restart their routine treatment immediately after each visit. participants will be admitted as an nhnn day case. following baseline assessments a localised attack of weakness will be induced by isometric exercise of the abductor digit minimi (adm) in the hand as per mcmanis protocol below. participants will be randomly assigned to either bumetanide or placebo for the first visit. identical appearing capsules will be prepared to blind both researcher and participant to treatment allocation. the assigned treatment will be taken by mouth at the onset of a focal attack defined as 40% decrement in adm cmap amplitude compared to the maximum cmap amplitude recorded during or after the exercise. during the admission each patient will be monitored according to the research protocol. at the end of the assessment protocol the participant will be discharged home. the duration of each admission will be approximately 6 hours the second assessment will follow an identical protocol to the first, but with the other treatment administered.

Eligibility criteria:
inclusion criteria: * at least 18 years of age; * diagnosis of genetically confirmed hypopp; * clinical symptoms or signs of active symptomatic disease (at least 1 attack in last 12 months); * practising an acceptable method of birth control for the duration of the trial. this will be addressed on patient information sheet for men and women (section 11.4.5); exclusion criteria: * inability or unwillingness to provide informed consent; * people older than 64 years old; * other conditions causing hand weakness which could interfere with study measurements (e.g. due to a stroke, trauma or arthritis) * patients with a history of cardiac disease, renal failure or moderate to severe hepatic disease. note: abnormalities in serum transaminases are common in people with hypopp as they arise from skeletal muscle rather than any specific liver abnormality. consequently, raised serum bilirubin \>20% above the baseline value will be used to identify abnormal liver function; * women who are pregnant or breast-feeding; * patients with a current or previous history of diabetes, porphyria, symptomatic hypotension, prostatic hypertrophy or difficulty with micturition, allergy to sulfonamides or thiazides; * patients on lithium, digoxin, nephro- or ototoxic drugs; * patients known to be allergic bumetanide or its excipients; * patients with a history of inadequately treated addison's disease; * patients participating in another interventional trial in the previous 1 month.

Keywords: hypokalemic periodic paralysis bumetanide periodic paralysis