Studies of the Variable Phenotypic Presentations of Rapid-Onset Dystonia Parkinsonism and Other Movement Disorders

Clinical, Genetic, and Cellular Consequences of Mutations in the NA,K-ATPase ATP1A3

The purposes of this study are to identify persons with rapid-onset dystonia-parkinsonism (RDP) or mutations of the RDP gene, document prevalence of the disease, and map its natural history.

Study Overview

• Status: Recruiting
• Conditions: Dystonia; Parkinsonism

Detailed Description

Rapid-onset dystonia-parkinsonism (RDP) is a rare, movement disorder with variable characteristics ranging from sudden onset (hours to days) of severe dystonic spasms to gradual onset of writer's cramp. RDP has elements of both dystonia and Parkinson's disease-two neurological diseases with motor and neuropsychological symptoms that hinder the quality of life. An internal trigger associated with extreme physiological stress has been reported prior to abrupt symptom onset of RDP.

This study, which is a continuation of an earlier study begun by Dr. Allison Brashear, aims to more clearly identify the characteristics associated with RDP and to explore whether mutations in the RDP gene are associated with atypical dystonias, Parkinson's disease, and other movement disorders.

The study involves in-person or remote (telemedicine) neurological assessments and blood samples for genetic analysis.

• Study Type: Observational
• Enrollment (Estimated): 198

Contacts and Locations

• Study Contact: Name: Rebecca Firth, MHA; Phone Number: 716-881-7461; Email: rsfirth@buffalo.edu

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95817
      • Recruiting
      • University of California, Davis
      • Contact: Eleonora Napoli, PhD; Email: enapoli@ucdavis.edu
      • Principal Investigator: Vicki Wheelock, MD
  • Florida
    • Miami, Florida, United States, 33136
      • Recruiting
      • University of Miami
      • Principal Investigator: Ihtsham Haq, MD
      • Contact: Silvia Vargas, CCRP; Phone Number: 305-243-3647; Email: s.vargasparra@med.miami.edu
  • New York
    • Buffalo, New York, United States, 14203
      • Recruiting
      • University at Buffalo
      • Contact: Rebecca Firth, MHA; Phone Number: 716-881-7461; Email: rsfirth@buffalo.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Selection will take place predominantly via primary care clinics, i.e., physician referrals when patients present with a movement disorder suspicious for RDP.

Description

Inclusion Criteria:

• clinical presentation consistent with ATP1A3 disease (RDP, AHC) or confirmed diagnosis of RDP or AHC

Exclusion Criteria:

• none

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
ATP1A3 Mutation; Those with RDP, AHC, unaffected carriers of ATP1A3 mutations, and non-carrying family members

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RDP Severity	History of symptom onset and duration will be obtained and current degree of severity assessed.	Visit 1 (baseline)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence of neuropsychiatric disease	Psychiatric interview and cognitive assessment will be performed to examine presence or absence of symptoms.	Will be assessed at Visits 1 (baseline) and 2 (24 months), approximately 2 years apart

Collaborators and Investigators

• Sponsor: State University of New York at Buffalo
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)
• Investigators: Principal Investigator: Allison Brashear, MD, Dean, University at Buffalo Jacobs School of Medicine and Biomedical Sciences

Publications and helpful links

General Publications

• Cook JF, Hill DF, Snively BM, Boggs N, Suerken CK, Haq I, Stacy M, McCall WV, Ozelius LJ, Sweadner KJ, Brashear A. Cognitive impairment in rapid-onset dystonia-parkinsonism. Mov Disord. 2014 Mar;29(3):344-50. doi: 10.1002/mds.25790. Epub 2014 Jan 16.
• Brashear A, Mink JW, Hill DF, Boggs N, McCall WV, Stacy MA, Snively B, Light LS, Sweadner KJ, Ozelius LJ, Morrison L. ATP1A3 mutations in infants: a new rapid-onset dystonia-Parkinsonism phenotype characterized by motor delay and ataxia. Dev Med Child Neurol. 2012 Nov;54(11):1065-7. doi: 10.1111/j.1469-8749.2012.04421.x. Epub 2012 Aug 28.

Helpful Links

• ATP1A3 diseases study website

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): July 31, 2027

Study Registration Dates

• First Submitted: May 20, 2008
• First Submitted That Met QC Criteria: May 21, 2008
• First Posted (Estimated): May 22, 2008

Study Record Updates

• Last Update Posted (Estimated): April 15, 2024
• Last Update Submitted That Met QC Criteria: April 11, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: parkinsonism; dystonia; AHC; rapid-onset dystonia-parkinsonism; RDP; Alternating Hemiplegia of Childhood
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Basal Ganglia Diseases; Movement Disorders; Dyskinesias; Dystonia; Dystonic Disorders; Parkinsonian Disorders
• Other Study ID Numbers: 1688159; BG05-556 (Other Identifier: Wake Forest University School of Medicine); 1R01NS058949-01A1 (U.S. NIH Grant/Contract); IRB00007686 (Other Identifier: Wake Forest University School of Medicine); 1704511 (Other Identifier: University of California, Davis IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No