- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02582476
Bumetanide in Hypokalaemic Periodic Paralysis
February 6, 2018 updated by: University College, London
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.
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
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 Type
Interventional
Enrollment (Anticipated)
12
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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London, United Kingdom, WC1N 3BG
- MRC Centre for Neuromuscular Disorders
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 64 years (Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Quadruple
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Focal attack severity one hour after treatment
Time Frame: The effect of treatment on 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.
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The effect of treatment on focal attack severity one hour after treatment
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Focal attack duration
Time Frame: 4 hours
|
This will be measured as the time between treatment administration until CMAP returns to 65% of peak CMAP within 4 hours following the treatment intake.
|
4 hours
|
The initial effect of treatment on severity of a focal attack
Time Frame: The initial effect of treatment on severity of a focal attack within the first two hours post treatment
|
The effect of treatment on severity of a focal attack within the first two hours (0-2).
This will be measured as CMAP amplitude (in percent compared to peak) area under the curve (AUC) from treatment administration until two hours post-treatment.
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The initial effect of treatment on severity of a focal attack within the first two hours post treatment
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The late effect of treatment on severity of a focal attack
Time Frame: The late effect of treatment on severity of a focal attack two to four hours post treatment
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The effect of treatment on severity of a focal attack within the last 2 hours (3-4).
This will be measured as CMAP amplitude (in percent) AUC from treatment administration during the third and the fourth hours post-treatment.
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The late effect of treatment on severity of a focal attack two to four hours post treatment
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Safety of Bumetanide assessed by vital signs, physical exam, potassium levels and self-reported adverse events
Time Frame: Safety of Bumetanide in HypoPP within 7 days of each study visit
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Baseline instantaneous potassium measurements as well as laboratory measurements, vital signs (blood pressure/heart rate) and a physical exam including MRC score are done prior to exercise and IMP intake.
During the first 4 hours following IMP intake vital signs (blood pressure/heart rate) and instantaneous serum potassium levels are measured frequently as per protocol.
Any reported symptoms or adverse events are recorded.
In addition intermittent electrophysiological recordings are taken from the non-exercised hand in order to identify the development of a major attack of paralysis early.
At the end of the observation period (4 hours after IMP intake) serum potassium levels are measured by the local hospital laboratory and a physical exam is performed including an MRC score.
Safety is also assessed by phone call evaluating adverse events reported by the participants and recorded in a diary occurring within 1 week following each visit.
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Safety of Bumetanide in HypoPP within 7 days of each study visit
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Doreen Fialho, MD, PhD, University College London Hospitals
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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.
- 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.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
January 1, 2015
Primary Completion (Actual)
May 9, 2017
Study Completion (Actual)
May 9, 2017
Study Registration Dates
First Submitted
August 11, 2015
First Submitted That Met QC Criteria
October 20, 2015
First Posted (Estimate)
October 21, 2015
Study Record Updates
Last Update Posted (Actual)
February 7, 2018
Last Update Submitted That Met QC Criteria
February 6, 2018
Last Verified
February 1, 2018
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Metabolic Diseases
- Nervous System Diseases
- Neurologic Manifestations
- Genetic Diseases, Inborn
- Musculoskeletal Diseases
- Muscular Diseases
- Neuromuscular Diseases
- Metabolism, Inborn Errors
- Metal Metabolism, Inborn Errors
- Paralyses, Familial Periodic
- Paralysis
- Hypokalemic Periodic Paralysis
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Natriuretic Agents
- Membrane Transport Modulators
- Diuretics
- Sodium Potassium Chloride Symporter Inhibitors
- Bumetanide
Other Study ID Numbers
- 120542
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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