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Abstract Details

RCT of Bumetanide in Hypokalaemic Periodic Paralysis (HypoPP) using abductor digiti minimi compound muscle action potential (CMAP) as an objective outcome measure

Introduction: Patients with HypoPP suffer debilitating attacks of muscle weakness accompanied by low serum potassium. The only treatment available during an acute attack is potassium replacement. Animal model work has suggested bumetanide as a potential new therapeutic agent due to its inhibition of the Na-K-Cl cotransporter 1,2.
Objectives: We conducted an RCT to assess efficacy and safety of bumetanide in treating an exercise induced attack of hand weakness in HypoPP.
Method: This was a randomised, double-blind, placebo-controlled phase II clinical trial with crossover design using abductor digiti minimi CMAP as an objective outcome measure. Patients attended on two occasions and underwent isometric exercise of ADM as per the McManis protocol. Once a CMAP decrement of 40% had occurred subjects received a single dose of 2mg bumetanide or placebo. Patients were then monitored for 4 hours after drug intake.
Results: Nine participants completed both trial visits. There was no statistically significant difference in CMAP amplitude (percent of maximum CMAP) between the Bumetanide (0.406) and placebo (0.349) groups at 1hour (p=0.27, primary outcome). There was also no statistically significant difference of CMAP amplitude between treatment groups assessing area under the curve for 0-2 hours and 2-4 hours after drug intake (effect estimate 0.043, p=0.3 and 0.085, p=0.1) Two participants recovered from the attack of weakness (reaching 65% of peak CMAP amplitude) within 4 hours following Bumetanide intake; none recovered following placebo intake.  There were no serious adverse events.
Conclusions: Bumetanide was safe but not effective to rescue a focal attack in an immobilised hand in the majority of patients. However, our data supports further studies of this agent. Identifier: NCT02582476

TitleForenamesSurnameInstitutionLead AuthorPresenter
DrRenata S.ScalcoMRC Centre for Neuromuscular Diseases, IoN, UCL
DrJasperMorrowMRC Centre for Neuromuscular Diseases, IoN, UCL
ProfMichael G.HannaMRC Centre for Neuromuscular Diseases, IoN, UCL
DrDoreenFialhoMRC Centre for Neuromuscular Diseases, IoN, UCL
Wu, F; Mi, W. and Cannon, S.C. (2013) 'Beneficial effects of bumetanide in a CaV1.1-R528H mouse model of hypokalaemic periodic paralysis': Brain, 136, pp. 3766-3774.
Wu, F; Mi, W. and Cannon, S.C. (2013) 'Bumetanide prevents transient decreases in muscle force in murine hypokalaemic periodic paralysis': Neurology, 80, pp. 1110-1116.