Hyper- and Hypokalemic Periodic Paralysis Study

Hypokalemic Periodic Paralysis Clinical Trial

— HYP-HOP  

Official title:

Dichlorphenamide vs. Placebo for Periodic Paralysis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00494507
• Other study ID #: R01NS045686-02
• Secondary ID: CRC
• Status: Completed
• Phase: Phase 3
• First received: June 27, 2007
• Last updated: November 5, 2015
• Start date: June 2007
• Est. completion date: May 2013

Study information

• Verified date: November 2015
• Source: University of Rochester
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 71
• Est. completion date: May 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hyperkalemic Periodic Paralysis
• Hypokalemic Periodic Paralysis
• Paralysis
• Paralysis, Hyperkalemic Periodic

Intervention

Drug:
• Dichlorphenamide (double-blind)
50mg tablet; maximum dosage 400mg/day
• Placebo (double-blind)
Inactive substance manufactured to look like Dichlorphenamide 50mg tablet
• Dichlorphenamide (open-label)
50mg tablet; maximum dosage 400mg/day

Locations

Country	Name	City	State
Italy	University of Milan	San Donato	Milan
United Kingdom	Institute of Neurology-Queen's Square	London
United States	Brigham & Women's Hospital	Boston	Massachusetts
United States	Ohio State University	Columbus	Ohio
United States	University of Texas Southwestern-Dallas	Dallas	Texas
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	UCLA Neurology	Los Angeles	California
United States	Columbia University Medical Center	New York	New York
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	University of California-San Francisco	San Francisco	California
United States	Washington University School of Medicine	St Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
University of Rochester	National Institute of Neurological Disorders and Stroke (NINDS)

Countries where clinical trial is conducted

United States,  Italy,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HYP Attack Rate	The number of distinct attacks per week over the final 8 weeks (Weeks 2-9) of the double-blind treatment period as self-reported by HYP participants.	8 weeks	No
Primary	HOP Attack Rate	The number of distinct attacks per week over the final 8 weeks (Weeks 2-9) of the double-blind treatment period as self-reported by HOP participants.	8 weeks	No
Secondary	HYP Severity-weighted Attack Rate	HYP participant severity-weighted attack rate is defined as the sum of average attack severity across all distinct attacks over the final 8 weeks (Weeks 2-9) of the double-blind treatment period divided by the number of weeks that the subject was followed. Attack severity (scored as 1-10 with increasing severity) is self-reported.	8 weeks	No
Secondary	HOP Severity-weighted Attack Rate	HOP participant severity-weighted attack rate is defined as the sum of average attack severity across all distinct attacks over the final 8 weeks (Weeks 2-9) of the double-blind treatment period divided by the number of weeks that the subject was followed. Attack severity (scored as 1-10 with increasing severity) is self-reported.	8 weeks	No
Secondary	HYP Attack Duration	HYP participant total attack duration per week, defined as the sum of attack durations across all distinct attacks over the final 8 weeks (Weeks 2-9) of the double-blind treatment period divided by the number of weeks that the subject was followed.	8 weeks	No
Secondary	HOP Attack Duration	HOP participant total attack duration per week, defined as the sum of attack durations across all distinct attacks over the final 8 weeks (Weeks 2-9) of the double-blind treatment period divided by the number of weeks that the subject was followed.	8 weeks	No
Secondary	HYP Endpoint of Acute Worsening	Increase in attack frequency or severity in HYP participants necessitating withdrawal from the initial nine-week double-blind treatment period and moving directly into the open-label phase.	0-9 weeks	No
Secondary	HOP Endpoint of Acute Worsening	Increase in attack frequency or severity in HOP participants necessitating withdrawal from the initial nine-week double-blind treatment period and moving directly into the open-label phase.	0-9 weeks	No