Hyper- and Hypokalemic Periodic Paralysis Study

NCT ID: NCT00494507

Last Updated: 2017-06-14

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

71 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-06-30

Study Completion Date

2013-05-31

Brief Summary

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The purpose of this study is to compare Dichlorphenamide with placebo (an inactive substance) for prevention of episodes and for improvement of strength in hyperkalemic (HYP) and hypokalemic (HOP) periodic paralysis. This study will also look at the long-term effects of Dichlorphenamide in periodic paralysis.

Detailed Description

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Periodic paralysis is a relatively rare, life-long disorder characterized by intermittent bouts of paralysis, progressive weakness, and diminished quality of life. Two drugs, acetazolamide (ACZ) and dichlorphenamide, have been prescribed to treat the disorder, however, dichlorphenamide is no longer available.

In this multi-center, parallel, randomized trial researchers will compare the effects of dichlorphenamide vs. placebo in patients with hyperkalemic (HYP) and hypokalemic (HOP) periodic paralysis.

The trial consists of two 9-week studies-one study will enroll persons with hyperkalemic periodic paralysis and the other study will enroll persons with hypokalemic periodic paralysis. Participants will be randomly assigned to one of two treatment groups: dichlorphenamide or placebo (an inactive substance). During the studies, participants will be asked to keep a daily diary to record the time, length, and severity of each episode of weakness (attack). The study coordinator will contact participants weekly to review the diary information.

The 9-week phase will be followed by a 1-year open-label dichlorphenamide extension without placebo to determine the long-term effects of dichlorphenamide on the course of the disease and on inter-attack weakness.

Duration of the trial for participants is approximately 65 weeks, including a screening phase to determine eligibility, the first 9-week treatment phase, and the one-year open-label extension phase.

Conditions

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Hyperkalemic Periodic Paralysis Hypokalemic Periodic Paralysis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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HYP Dichlorphenamide

Hyperkalemic participants were randomized to Dichlorphenamide for a 9 week double-blind phase. All participants then received Dichlorphenamide for a 52 week open-label phase.

Group Type ACTIVE_COMPARATOR

Dichlorphenamide (double-blind)

Intervention Type DRUG

50mg tablet; maximum dosage 400mg/day

Dichlorphenamide (open-label)

Intervention Type DRUG

50mg tablet; maximum dosage 400mg/day

HYP Placebo

Hyperkalemic participants were randomized to Placebo for a 9 week double-blind phase. All participants then received Dichlorphenamide for a 52 week open-label phase.

Group Type PLACEBO_COMPARATOR

Placebo (double-blind)

Intervention Type DRUG

Inactive substance manufactured to look like Dichlorphenamide 50mg tablet

Dichlorphenamide (open-label)

Intervention Type DRUG

50mg tablet; maximum dosage 400mg/day

HOP Dichlorphenamide

Hypokalemic participants were randomized to Dichlorphenamide for a 9 week double-blind phase. All participants then received Dichlorphenamide for a 52 week open-label phase.

Group Type ACTIVE_COMPARATOR

Dichlorphenamide (double-blind)

Intervention Type DRUG

50mg tablet; maximum dosage 400mg/day

Dichlorphenamide (open-label)

Intervention Type DRUG

50mg tablet; maximum dosage 400mg/day

HOP Placebo

Hypokalemic participants were randomized to Placebo for a 9 week double-blind phase. All participants then received Dichlorphenamide for a 52 week open-label phase.

Group Type PLACEBO_COMPARATOR

Placebo (double-blind)

Intervention Type DRUG

Inactive substance manufactured to look like Dichlorphenamide 50mg tablet

Dichlorphenamide (open-label)

Intervention Type DRUG

50mg tablet; maximum dosage 400mg/day

Interventions

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Dichlorphenamide (double-blind)

50mg tablet; maximum dosage 400mg/day

Intervention Type DRUG

Placebo (double-blind)

Inactive substance manufactured to look like Dichlorphenamide 50mg tablet

Intervention Type DRUG

Dichlorphenamide (open-label)

50mg tablet; maximum dosage 400mg/day

Intervention Type DRUG

Other Intervention Names

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Daranide Daranide

Eligibility Criteria

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Inclusion Criteria

* Genetically definite, clinically definite or clinically probable Hyperkalemic or Hypokalemic Periodic Paralysis as outlined in the protocol
* Male and female participants, age 18 and older who are able to comply with the study conditions.
* Participants who have distinct regular episodes of weakness with an average frequency of \> or = to 1 a week and \< or = to 3 a day either on or off treatment, whichever is higher
* Normal thyroid-stimulating hormone (TSH) level

Exclusion Criteria

* Evidence for Andersen-Tawil syndrome (any one of the following 3 criteria)

1. Prolonged QT interval or complex ventricular ectopy between attacks
2. Distinctive physical features (2 of the following 5)

1. Low set ears
2. Short stature
3. Hypo-/micrognathia
4. Clinodactyly
5. Hypo-/hypertelorism
3. KIR 2.1 gene mutation
* Coincidental renal, hepatic, active thyroid disease, restrictive or obstructive lung disease, other neuromuscular disease, or heart disease
* Chronic, non-congestive, angle-closure glaucoma
* Use of any of the following medications for reasons other than treatment of periodic paralysis: diuretics, antiarrhythmics, corticosteroids, beta-blockers, calcium channel blockers, antiepileptics, magnesium
* History of life-threatening episodes of respiratory muscle weakness or cardiac arrhythmias during attacks
* Pregnancy
* Known mutation in the alpha subunit of the sodium channel gene in hypokalemic periodic paralysis patients
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role collaborator

University of Rochester

OTHER

Sponsor Role lead

Responsible Party

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Robert Griggs, MD

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Robert C. Griggs, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Rochester

Rabi Tawil, M.D.

Role: PRINCIPAL_INVESTIGATOR

Co-Principal Investigator, University of Rochester

Michael McDermott, Ph.D.

Role:

Biostatistician, University of Rochester

Locations

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UCLA Neurology

Los Angeles, California, United States

Site Status

University of California-San Francisco

San Francisco, California, United States

Site Status

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

Brigham & Women's Hospital

Boston, Massachusetts, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

University of Rochester

Rochester, New York, United States

Site Status

Ohio State University

Columbus, Ohio, United States

Site Status

University of Texas Southwestern-Dallas

Dallas, Texas, United States

Site Status

University of Milan

San Donato, Milan, Italy

Site Status

Institute of Neurology-Queen's Square

London, , United Kingdom

Site Status

Countries

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United States Italy United Kingdom

Other Identifiers

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CRC

Identifier Type: OTHER

Identifier Source: secondary_id

R01NS045686-02

Identifier Type: NIH

Identifier Source: org_study_id

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