Hyper- and Hypokalemic Periodic Paralysis Study

NCT00494507 | Completed Phase 3 Results DMC

• 2 other identifiers: R01NS045686-02CRC
• Study Type: interventional
• Target: 71
• Locations: 3 countries
• Sites: 12

Brief 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.

Conditions

Hyperkalemic Periodic Paralysis; Hypokalemic Periodic Paralysis

Keywords

periodic paralysis; dichlorphenamide

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Secondary Outcomes (18)

• HYP Severity-weighted Attack Rate

  8 weeks

• HOP Severity-weighted Attack Rate

  8 weeks

• HYP Attack Duration

  8 weeks

• HOP Attack Duration

  8 weeks

• HYP Endpoint of Acute Worsening

  0-9 weeks

Study Arms (4)

HYP Dichlorphenamide

ACTIVE COMPARATOR

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.

Drug: Dichlorphenamide (double-blind); Drug: Dichlorphenamide (open-label)

HYP Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo (double-blind); Drug: Dichlorphenamide (open-label)

HOP Dichlorphenamide

ACTIVE COMPARATOR

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.

Drug: Dichlorphenamide (double-blind); Drug: Dichlorphenamide (open-label)

HOP Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo (double-blind); Drug: Dichlorphenamide (open-label)

Interventions

Dichlorphenamide (double-blind) DRUG

50mg tablet; maximum dosage 400mg/day

Also known as: Daranide

HOP Dichlorphenamide; HYP Dichlorphenamide

Placebo (double-blind) DRUG

Inactive substance manufactured to look like Dichlorphenamide 50mg tablet

HOP Placebo; HYP Placebo

Dichlorphenamide (open-label) DRUG

50mg tablet; maximum dosage 400mg/day

Also known as: Daranide

HOP Dichlorphenamide; HOP Placebo; HYP Dichlorphenamide; HYP Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Evidence for Andersen-Tawil syndrome (any one of the following 3 criteria)
• Prolonged QT interval or complex ventricular ectopy between attacks
• Distinctive physical features (2 of the following 5)
• Low set ears
• Short stature
• Hypo-/micrognathia
• Clinodactyly
• Hypo-/hypertelorism
• 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

Sponsors & Collaborators

• University of Rochester: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (12)

UCLA Neurology

Los Angeles, California, 90095, United States

Location

University of California-San Francisco

San Francisco, California, 94143, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Brigham & Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

University of Texas Southwestern-Dallas

Dallas, Texas, 75390, United States

Location

University of Milan

San Donato, Milan, Italy

Location

Institute of Neurology-Queen's Square

London, United Kingdom

Location

MeSH Terms

Conditions

Paralysis, Hyperkalemic Periodic; Hypokalemic Periodic Paralysis

Interventions

Dichlorphenamide; Double-Blind Method

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; Sulfones; Sulfur Compounds; Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Limitations and Caveats

Sample sizes in the trial were limited by slow recruitment and the trial was concluded before attainment of the target numbers of subjects. Statistical analyses were conducted using smaller group sizes than planned, particularly for HYP subjects.

Results Point of Contact

• Title: Robert Griggs, MD
• Organization: University of Rochester

robert_griggs@urmc.rochester.edu

585-275-3707

Study Officials

• Robert C. Griggs, M.D.

  University of Rochester

  PRINCIPAL INVESTIGATOR

• Rabi Tawil, M.D.

  Co-Principal Investigator, University of Rochester

  PRINCIPAL INVESTIGATOR

• Michael McDermott, Ph.D.

  Biostatistician, University of Rochester

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 27, 2007
• First Posted: June 29, 2007
• Study Start: June 1, 2007
• Primary Completion: April 1, 2013
• Study Completion: May 1, 2013
• Last Updated: June 14, 2017
• Results First Posted: May 30, 2014

Record last verified: 2017-05

Locations

US (10); IT (1); GB (1)