Characteristics of Andersen-Tawil Syndrome - Full Text View

Sponsors and Collaborators:	Office of Rare Diseases (ORD) Rare Diseases Clinical Research Network
Information provided by:	Office of Rare Diseases (ORD)
ClinicalTrials.gov Identifier:	NCT00521794

Purpose

Andersen-Tawil Syndrome (ATS) is a rare, genetic disorder that causes episodes of muscle weakness, potentially life-threatening changes in heart rhythm, and developmental abnormalities. Disease symptoms can vary, the cause of some ATS cases remains unknown, and no specific treatment has been identified.

The purpose of this multi-site study is to better characterize ATS, establish whether symptoms change over time, and determine if symptoms are related to a mutation in the KCNJ2 gene.

Condition
Andersen-Tawil Syndrome Andersen Syndrome

Study Type:	Observational
Study Design:	Cohort, Prospective
Official Title:	Andersen-Tawil Syndrome: Genotype-Phenotype Correlation and Longitudinal Study

Resource links provided by NLM:

Genetics Home Reference related topics: Andersen-Tawil syndrome Brugada syndrome Jervell and Lange-Nielsen syndrome Romano-Ward syndrome short QT syndrome

U.S. FDA Resources

Further study details as provided by Office of Rare Diseases (ORD):

Biospecimen Retention: Samples With DNA

Biospecimen Description:

Blood samples

Estimated Enrollment:	50
Study Start Date:	August 2007
Estimated Study Completion Date:	July 2009
Estimated Primary Completion Date:	July 2009 (Final data collection date for primary outcome measure)

Detailed Description:

ATS is an ion channel disorder that causes episodes of muscle weakness and potentially life-threatening heart arrhythmias for which no treatment has been identified. The majority of ATS cases are caused by a mutation in the KCNJ2 gene; other cases result from unknown causes. The KCNJ2 gene mutation alters potassium channels in such a way that it disrupts the flow of potassium ions in skeletal and heart muscle. This can lead to the characteristic periodic paralysis and irregular heart rhythms. The purpose of this study is to better define the genetic basis, clinical features, and disease progression of ATS. The study will also establish clinically relevant endpoints for use in future clinical studies.

This observational study will last 2 years and will involve three study visits. The first visit will entail a 1.5- to 3.5-day inpatient stay; the length of stay will depend on whether a participant has been taking medications for their symptoms of weakness. Participants will be asked to discontinue use of such medications during the inpatient stay. Participants will not be asked to stop any medications that they may be taking for heart symptoms. This first study visit will include a medical history, a quality of life questionnaire, a physical exam, and muscle strength testing. Nerve, muscle, and heart activity will also be measured, and blood will be drawn for laboratory tests and optional DNA analysis. The second and third study visits will take place

1 and 2 years after the initial study visit and will include the same evaluations. During the 8 weeks following each study visit, participants will record in a telephone diary any muscle and heart symptoms that they experience. During the 1 week after both yearly visits, participants will also undergo an outpatient heart rhythm evaluation. A study coordinator will contact participants once a month by phone over the course of the study to review symptoms.

Eligibility

Ages Eligible for Study:	10 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

Individuals with a clinically confirmed diagnosis of Andersen-Tawil Syndrome (ATS) enrolled across seven sites in the United States, England, and Canada

Criteria

Inclusion Criteria:

Clinically confirmed diagnosis of ATS as defined by at least two of the following three criteria:
1. Presence of clear-cut episodes of transient muscle weakness with or without a fixed deficit, typically following exertion or prolonged rest OR atypical history with otherwise typical exam findings (absent reflexes with normal sensation during an episode) OR unexplained hypokalemia between episodes OR abnormal long-exercise nerve conduction study
2. Heart conduction defects: prolonged QTc interval on 12-lead electrocardiogram OR ventricular ectopy, including uniform or multifocal PVCs, polymorphic VT, or bidirectional VT
3. Presence of two or more of the following physical features: low set ears, hypertelorism, small mandible, clinodactyly, syndactyly, micromelia of hands or feet --OR--
Meets one of the above three criteria and has at least one family member with two of the criteria --OR--
Does not meet the above three criteria, but possesses a mutation in the KCNJ2 gene

Exclusion Criteria:

Less than 10 years of age
Pregnant

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00521794

Contacts

Contact: Kimberly Hart, MA

585-275-3767

Kim_Hart@URMC.Rochester.edu

Locations

United States, California
University of California, San Francisco	Recruiting
San Francisco, California, United States, 94143
Contact: Kristin Wong
Principal Investigator: Jeffrey W. Ralph, MD
United States, Kansas
University of Kansas Medical Center	Recruiting
Kansas City, Kansas, United States, 66160
Contact: Laura Herbelin
Principal Investigator: Richard Barohn, MD
United States, Massachusetts
Brigham and Women's Hospital	Recruiting
Boston, Massachusetts, United States, 02115
Contact: Kristen Whiteside
Principal Investigator: Anthony Amato, MD
United States, New York
University of Rochester School of Medicine and Dentistry	Recruiting
Rochester, New York, United States, 14642
Contact: Kimberly Hart 585-275-3767 Kim_Hart@urmc.rochester.edu
Principal Investigator: Robert C. Griggs, MD
Principal Investigator: Emma Ciafaloni, MD
United States, Texas
University of Texas Southwestern Medical Center	Recruiting
Dallas, Texas, United States, 75390
Contact: Nina Gorham
Principal Investigator: Jaya Trivedi, MD
Canada, Ontario
London Health Sciences Centre	Recruiting
London, Ontario, Canada, N6A 5A5
Contact: Kori LaDonna
Principal Investigator: Angelika Hahn, MD
United Kingdom
Institute of Neurology and National Hospital for Neurology	Recruiting
London, United Kingdom
Contact: Doreen Fialho, MD
Principal Investigator: Michael Hanna, MD

Sponsors and Collaborators

Office of Rare Diseases (ORD)

Rare Diseases Clinical Research Network

Investigators

Study Chair:	Emma Ciafaloni, MD	University of Rochester
Principal Investigator:	Robert C. Griggs, MD	University of Rochester

More Information

Publications:

Tawil R, Ptacek LJ, Pavlakis SG, DeVivo DC, Penn AS, Ozdemir C, Griggs RC. Andersen's syndrome: potassium-sensitive periodic paralysis, ventricular ectopy, and dysmorphic features. Ann Neurol. 1994 Mar;35(3):326-30.

Sansone V, Griggs RC, Meola G, Ptacek LJ, Barohn R, Iannaccone S, Bryan W, Baker N, Janas SJ, Scott W, Ririe D, Tawil R. Andersen's syndrome: a distinct periodic paralysis. Ann Neurol. 1997 Sep;42(3):305-12.

Tristani-Firouzi M, Jensen JL, Donaldson MR, Sansone V, Meola G, Hahn A, Bendahhou S, Kwiecinski H, Fidzianska A, Plaster N, Fu YH, Ptacek LJ, Tawil R. Functional and clinical characterization of KCNJ2 mutations associated with LQT7 (Andersen syndrome). J Clin Invest. 2002 Aug;110(3):381-8.

Responsible Party:	University of Rochester School of Medicine ( Rabi Tawil, MD )
Study ID Numbers:	RDCRN 5301, 5 U54 RR019482-02
Study First Received:	August 24, 2007
Last Updated:	April 16, 2009
ClinicalTrials.gov Identifier:	NCT00521794 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by Office of Rare Diseases (ORD):

Arrhythmia
Muscle Weakness
Periodic Paralysis
Channelopathy

Study placed in the following topic categories:

Paralysis
Heart Diseases
Cardiovascular Abnormalities
Andersen Syndrome
Asthenia
Andersen Tawil Syndrome

Long QT Syndrome
Congenital Abnormalities
Muscle Weakness
Heart Defects, Congenital
Arrhythmias, Cardiac

Additional relevant MeSH terms:

Heart Diseases
Pathologic Processes
Disease
Cardiovascular Abnormalities
Andersen Syndrome
Syndrome

Cardiovascular Diseases
Long QT Syndrome
Congenital Abnormalities
Heart Defects, Congenital
Arrhythmias, Cardiac

ClinicalTrials.gov processed this record on July 06, 2009