Bumetanide in Hypokalaemic Periodic Paralysis

Brief Title

Bumetanide in Hypokalaemic Periodic Paralysis

Official Title

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

Brief 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.
    

Detailed Description

      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.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Focal attack severity one hour after treatment

Secondary Outcome

 Focal attack duration

Condition

Hypokalemic Periodic Paralysis

Intervention

Bumetanide


Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

12

Start Date

January 2015

Completion Date

May 9, 2017

Primary Completion Date

May 9, 2017

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.
      

Gender

All

Ages

18 Years - 64 Years

Accepts Healthy Volunteers

No

Contacts

Doreen Fialho, MD, PhD, , 

Location Countries

United Kingdom

Location Countries

United Kingdom

Administrative Informations


NCT ID

NCT02582476

Organization ID

120542


Responsible Party

Sponsor

Study Sponsor

University College, London


Study Sponsor

Doreen Fialho, MD, PhD, Principal Investigator, University College London Hospitals


Verification Date

February 2018