Hypokalemic Periodic ParalysisPhase 2NCT02582476
Bumetanide in Hypokalaemic Periodic Paralysis
A Phase 2 study testing Bumetanide in people with Hypokalemic Periodic Paralysis, run by University College, London at 1 site in United Kingdom.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 64 years
- Conditions the study is for
- Hypokalemic Periodic Paralysis
- What is being tested?
- Bumetanide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jan 2015to 9 May 2017
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 64 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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);
Who cannot join
- 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;
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- 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.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
MRC Centre for Neuromuscular Disorders
London, WC1N 3BG
About this study
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
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.
Read the 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.
- Conditions
- Hypokalemic Periodic Paralysis
- Being tested
- Bumetanide, Placebo
- Keywords
- Hypokalemic Periodic Paralysis, Bumetanide, Periodic Paralysis
- Medical subject headings
- Hypokalemic Periodic Paralysis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BumetanideDrug
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.
PlaceboDrug
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.
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: The effect of treatment on focal attack severity one hour after treatment
Secondary outcomes (4)
Focal attack duration
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.
Measured: 4 hours
The initial effect of treatment on severity of a focal attack
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.
Measured: 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 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.
Measured: 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
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.
Measured: Safety of Bumetanide in HypoPP within 7 days of each study visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2015 (estimated)
- Study startJan 2015
- Primary completion9 May 2017
- Study completion9 May 2017
Why it stopped: Slow enrolment and end of funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Hypokalemic Periodic ParalysisStudies of the same condition, open and under way.
- More trials run by University College, LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Doreen Fialho, MD, PhD, Principal investigator, University College London Hospitals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02582476
- Sponsor's protocol ID
- 120542
- Status last verified
- Feb 2018
- First submitted
- 11 Aug 2015
- Last updated
- 7 Feb 2018
- Results posted
- No
- Data monitoring committee
- Yes
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.
PubMed 24142145Wu 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.
PubMed 23427324
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02582476
- Acronym / sponsor ID
- 120542
- Conditions
- Hypokalemic Periodic Paralysis
- Keywords
- Hypokalemic Periodic Paralysis, Bumetanide, Periodic Paralysis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow enrolment and end of funding
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Study start
- Jan 2015
- Primary completion
- 9 May 2017 (actual)
- Study completion
- 9 May 2017 (actual)
- First posted
- 21 Oct 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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);
Key exclusion criteria (10 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BumetanideParticipants 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. | Drug | – |
| PlaceboParticipants 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. | Drug | – |
Primary outcome
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.
4 secondary outcomes
Focal attack duration
Time frame: 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 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
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
Results and safety
The study was stopped early (reason given: Slow enrolment and end of funding). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2018.
- Background: PubMed 24142145Wu 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.
- Background: PubMed 23427324Wu 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.
- Queen Square TrialLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Doreen Fialho, MD, PhD principal investigator
University College London Hospitals
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bumetanide in people with Hypokalemic Periodic Paralysis, run by University College, London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 7 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Slow enrolment and end of funding). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Focal attack severity one hour after treatment (time frame: The effect of treatment on focal attack severity one hour after treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02582476, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Feb 2018.