Bumetanide in Hypokalaemic Periodic Paralysis

NCT02582476 | Terminated Phase 2 DMC

• 1 other identifier: 120542
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Hypokalemic Periodic Paralysis

Keywords

Hypokalemic Periodic Paralysis; Bumetanide; Periodic Paralysis

Outcome Measures

Primary Outcomes (1)

• Focal attack severity one hour after treatment

  This will be measured as CMAP amplitude expressed as a percent of peak CMAP during or after the McManis exercise.

  The effect of treatment on focal attack severity one hour after treatment

Secondary Outcomes (4)

• Focal attack duration

  4 hours

• The initial effect of treatment on severity of a focal attack

  The initial effect of treatment on severity of a focal attack within the first two hours post treatment

• The late effect of treatment on severity of a focal attack

  The late effect of treatment on severity of a focal attack two to four hours post treatment

• Safety of Bumetanide assessed by vital signs, physical exam, potassium levels and self-reported adverse events

  Safety of Bumetanide in HypoPP within 7 days of each study visit

Interventions

Bumetanide DRUG

Participants will be randomly assigned to either bumetanide or placebo for the first visit. 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. The second assessment will follow an identical protocol to the first, but with the other treatment administered.

Placebo DRUG

Participants will be randomly assigned to either bumetanide or placebo for the first visit. 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. The second assessment will follow an identical protocol to the first, but with the other treatment administered.

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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);

You may not qualify if:

• 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.

Sponsors & Collaborators

• University College, London: lead

Study Sites (1)

MRC Centre for Neuromuscular Disorders

London, WC1N 3BG, United Kingdom

Location

Related Publications (2)

• Wu F, Mi W, Cannon SC. Beneficial effects of bumetanide in a CaV1.1-R528H mouse model of hypokalaemic periodic paralysis. Brain. 2013 Dec;136(Pt 12):3766-74. doi: 10.1093/brain/awt280. Epub 2013 Oct 18.

  PMID: 24142145 BACKGROUND

• Wu F, Mi W, Cannon SC. Bumetanide prevents transient decreases in muscle force in murine hypokalemic periodic paralysis. Neurology. 2013 Mar 19;80(12):1110-6. doi: 10.1212/WNL.0b013e3182886a0e. Epub 2013 Feb 20.

  PMID: 23427324 BACKGROUND

Related Links

• Queen Square Trial

MeSH Terms

Conditions

Hypokalemic Periodic Paralysis

Interventions

Bumetanide

Condition Hierarchy (Ancestors)

Paralyses, Familial Periodic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Metal Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; meta-Aminobenzoates; Aminobenzoates; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds

Study Officials

• Doreen Fialho, MD, PhD

  University College London Hospitals

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2015
• First Posted: October 21, 2015
• Study Start: January 1, 2015
• Primary Completion: May 9, 2017
• Study Completion: May 9, 2017
• Last Updated: February 7, 2018

Record last verified: 2018-02

Locations

GB (1)