A Randomised, Double-blind, Placebo-controlled, Phase II Clinical Trial With a Cross-over Design Assessing Efficacy of a Single Dose of Bumetanide in Reducing Focal Attack Severity in Hypokalaemic Periodic Paralysis Assessed Using the McManis Protocol
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.
Focal attack severity one hour after treatment
Focal attack duration
Hypokalemic Periodic Paralysis
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
May 9, 2017
Primary Completion Date
May 9, 2017
- 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
- 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);
- 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.
18 Years - 64 Years
Accepts Healthy Volunteers
Doreen Fialho, MD, PhD, ,
University College, London
Doreen Fialho, MD, PhD, Principal Investigator, University College London Hospitals