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Phenotype/Genotype Correlations in Movement Disorders

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00018889
Recruitment Status : Recruiting
First Posted : July 9, 2001
Last Update Posted : December 30, 2021
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )

Brief Summary:
The goal of this protocol is to identify families with inherited movement disorders and evaluate disease manifestations to establish an accurate clinical diagnosis by using newest technological advances and investigate the underlying molecular mechanisms. Studies of inherited movement disorders in large families with good genealogical records are especially valuable. Patients with diseases of known molecular basis will be genotyped in order to investigate phenotype/genotype correlation. Patients with disease of unknown or incomplete genetic characterization will be studied with a hope of contributing to the identification of specific disease-causing genes and genetic mechanisms responsible for a specific disorder.

Condition or disease
Movement Disorder

Detailed Description:

Objective: The primary objective of this study is to perform phenotypic and genotypic characterizations of patients and family members with a known or suspected diagnosis of a movement disorder and screen for eligibility to participate in other movement disorder related protocols:

14-N-0086 Deep brain stimulation therapy in movement disorders

11-N-0211 Deep brain stimulation surgery for movement disorders

12-N-0031 Imaging biomarkers in Parkinson s Disease

93-N-0202 Diagnosis and natural history protocol for patients with different neurological conditions

17-N-0076: Does N-Acetylcysteine decrease spontaneous oxidation of central neural dopamine in Parkinson s Disease?

17-N-0035: Clinical and physiological studies of tremor syndromes

00-N-0043: Clinical and molecular manifestations of inherited neurologic disorders

03-AG-N-329 (NIA): The genetic characterization of movement disorders and dementias

The secondary goals of this protocol are to learn more about genetic causes of movement disorders and their phenotypic associations; identify patients and families with inherited movement disorders; evaluate disease manifestations to establish an accurate clinical diagnosis; and to investigate the underlying molecular mechanisms. Studies of inherited movement disorders in large families with well-documented genealogical records are especially valuable. The study will also assess a series of exploratory peripheral biomarkers, including, but not limited to, those delineated by DNA, RNA, protein, and/or metabolite alterations in an effort to more accurately predict those with, or at risk of having, the specific neurological disease.

Study population: Subjects older than 2 years old with movement disorders and their family members will be enrolled. Patients with diseases of known molecular basis will be genotyped in order to investigate phenotype/genotype correlations. Patients with disease of unknown or incomplete genetic characterization will be studied with a hope of contributing to the identification of specific disease-causing genes and genetic mechanisms and/or peripheral bio-signatures involved in a particular disorder.

Design:

This is an observational diagnostic study of movement disorders and their progression and pathophysiology.

Outcome measures: Determination of phenotype/genotype correlations in specific movement disorders, referral of patients and/or family members for participation in other NIH studies, gene identification if not known, gene expression and protein, metabolite and nucleic acid levels, collection of blood cells and generation of induced pluripotent stem cell lines, and establishment of a clinical diagnosis when possible.

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Study Type : Observational
Estimated Enrollment : 2500 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Phenotype/Genotype Correlations in Movement Disorders
Actual Study Start Date : October 22, 2001

Resource links provided by the National Library of Medicine


Group/Cohort
1
Patients age 2 years and older with a clinical or suspected diagnosis of movement disorder



Primary Outcome Measures :
  1. The primary outcome measure is the phenotypic and genotypic characterizations of patients and family members with movement disorders. [ Time Frame: 10 Years ]
    Characterizations to determine their eligibility for inclusion in other NIH protocols.


Secondary Outcome Measures :
  1. Identification of specific peripheral blood biomarkers in plasma of patients with or without PD that would improve the diagnostic accuracy, especially in subjects at risk of developing the disorder in the future
  2. Identification of peripheral alpha-synuclein via histology of skin biopsies
  3. Identification of new genes through newer techniques such as whole exome and whole genome to identify the genetic cause of a neurologic condition in an individual or family.
  4. Identification of new genes and/or peripheral blood biomarkers associated with movement disorders.
  5. Identification of disease-specific biomarkers in stem cells derived from patient peripheral blood mononuclear cells or fibroblast lines.
  6. Identification clinical correlations between phenotype and genotype


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   2 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
-Patients age 2 years and older with a clinical or suspected diagnosis of movement disorder.-Accrual ceiling-2500-Dropouts will not be replaced-Self-referral is allowed-NIH employees may participate if they meet the eligibility
Criteria
  • INCLUSION CRITERIA:

Individuals with known or suspected inherited movement disorders.

Family members of movement disorders patients

EXCLUSION CRITERIA:

Pregnant women will be excluded from MRI or X-ray studies

Children less than 2 years of age

Those who cannot provide their own consent or appoint a Durable Power of Attorney (DPA).

Exclusion criteria for MRI

  • Presence of metal in subject's body which would make having an MRI scan unsafe, such as pacemakers, stimulators, pumps, aneurysm clips, metallic prostheses, artificial heart valves, cochlear implants, shrapnel fragments, or if subject was a welder or metal worker (since small metal fragments in the eye may be present).
  • Subject is uncomfortable in small closed spaces (have claustrophobia) so that they would feel uncomfortable in the MRI machine.
  • Unable to lie comfortably on back for up to 1 hour.
  • Are pregnant
  • Under 12 years of age

There is no general exclusion for NIH employees. Inclusion/exclusion criteria will be checked before enrollment in each sub-study to ensure that participants remain eligible.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00018889


Contacts
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Contact: Mae Brooks (301) 496-4604 brooksm@ninds.nih.gov
Contact: Debra J Ehrlich, M.D. (301) 443-7888 debra.ehrlich@nih.gov

Locations
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United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)    800-411-1222 ext TTY8664111010    prpl@cc.nih.gov   
Sponsors and Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
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Principal Investigator: Debra J Ehrlich, M.D. National Institute of Neurological Disorders and Stroke (NINDS)
Additional Information:
Publications:
Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, Yandell M, Evans CA, Holt RA, Gocayne JD, Amanatides P, Ballew RM, Huson DH, Wortman JR, Zhang Q, Kodira CD, Zheng XH, Chen L, Skupski M, Subramanian G, Thomas PD, Zhang J, Gabor Miklos GL, Nelson C, Broder S, Clark AG, Nadeau J, McKusick VA, Zinder N, Levine AJ, Roberts RJ, Simon M, Slayman C, Hunkapiller M, Bolanos R, Delcher A, Dew I, Fasulo D, Flanigan M, Florea L, Halpern A, Hannenhalli S, Kravitz S, Levy S, Mobarry C, Reinert K, Remington K, Abu-Threideh J, Beasley E, Biddick K, Bonazzi V, Brandon R, Cargill M, Chandramouliswaran I, Charlab R, Chaturvedi K, Deng Z, Di Francesco V, Dunn P, Eilbeck K, Evangelista C, Gabrielian AE, Gan W, Ge W, Gong F, Gu Z, Guan P, Heiman TJ, Higgins ME, Ji RR, Ke Z, Ketchum KA, Lai Z, Lei Y, Li Z, Li J, Liang Y, Lin X, Lu F, Merkulov GV, Milshina N, Moore HM, Naik AK, Narayan VA, Neelam B, Nusskern D, Rusch DB, Salzberg S, Shao W, Shue B, Sun J, Wang Z, Wang A, Wang X, Wang J, Wei M, Wides R, Xiao C, Yan C, Yao A, Ye J, Zhan M, Zhang W, Zhang H, Zhao Q, Zheng L, Zhong F, Zhong W, Zhu S, Zhao S, Gilbert D, Baumhueter S, Spier G, Carter C, Cravchik A, Woodage T, Ali F, An H, Awe A, Baldwin D, Baden H, Barnstead M, Barrow I, Beeson K, Busam D, Carver A, Center A, Cheng ML, Curry L, Danaher S, Davenport L, Desilets R, Dietz S, Dodson K, Doup L, Ferriera S, Garg N, Gluecksmann A, Hart B, Haynes J, Haynes C, Heiner C, Hladun S, Hostin D, Houck J, Howland T, Ibegwam C, Johnson J, Kalush F, Kline L, Koduru S, Love A, Mann F, May D, McCawley S, McIntosh T, McMullen I, Moy M, Moy L, Murphy B, Nelson K, Pfannkoch C, Pratts E, Puri V, Qureshi H, Reardon M, Rodriguez R, Rogers YH, Romblad D, Ruhfel B, Scott R, Sitter C, Smallwood M, Stewart E, Strong R, Suh E, Thomas R, Tint NN, Tse S, Vech C, Wang G, Wetter J, Williams S, Williams M, Windsor S, Winn-Deen E, Wolfe K, Zaveri J, Zaveri K, Abril JF, Guigó R, Campbell MJ, Sjolander KV, Karlak B, Kejariwal A, Mi H, Lazareva B, Hatton T, Narechania A, Diemer K, Muruganujan A, Guo N, Sato S, Bafna V, Istrail S, Lippert R, Schwartz R, Walenz B, Yooseph S, Allen D, Basu A, Baxendale J, Blick L, Caminha M, Carnes-Stine J, Caulk P, Chiang YH, Coyne M, Dahlke C, Mays A, Dombroski M, Donnelly M, Ely D, Esparham S, Fosler C, Gire H, Glanowski S, Glasser K, Glodek A, Gorokhov M, Graham K, Gropman B, Harris M, Heil J, Henderson S, Hoover J, Jennings D, Jordan C, Jordan J, Kasha J, Kagan L, Kraft C, Levitsky A, Lewis M, Liu X, Lopez J, Ma D, Majoros W, McDaniel J, Murphy S, Newman M, Nguyen T, Nguyen N, Nodell M, Pan S, Peck J, Peterson M, Rowe W, Sanders R, Scott J, Simpson M, Smith T, Sprague A, Stockwell T, Turner R, Venter E, Wang M, Wen M, Wu D, Wu M, Xia A, Zandieh A, Zhu X. The sequence of the human genome. Science. 2001 Feb 16;291(5507):1304-51. Erratum in: Science 2001 Jun 5;292(5523):1838.
Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, Doyle M, FitzHugh W, Funke R, Gage D, Harris K, Heaford A, Howland J, Kann L, Lehoczky J, LeVine R, McEwan P, McKernan K, Meldrim J, Mesirov JP, Miranda C, Morris W, Naylor J, Raymond C, Rosetti M, Santos R, Sheridan A, Sougnez C, Stange-Thomann Y, Stojanovic N, Subramanian A, Wyman D, Rogers J, Sulston J, Ainscough R, Beck S, Bentley D, Burton J, Clee C, Carter N, Coulson A, Deadman R, Deloukas P, Dunham A, Dunham I, Durbin R, French L, Grafham D, Gregory S, Hubbard T, Humphray S, Hunt A, Jones M, Lloyd C, McMurray A, Matthews L, Mercer S, Milne S, Mullikin JC, Mungall A, Plumb R, Ross M, Shownkeen R, Sims S, Waterston RH, Wilson RK, Hillier LW, McPherson JD, Marra MA, Mardis ER, Fulton LA, Chinwalla AT, Pepin KH, Gish WR, Chissoe SL, Wendl MC, Delehaunty KD, Miner TL, Delehaunty A, Kramer JB, Cook LL, Fulton RS, Johnson DL, Minx PJ, Clifton SW, Hawkins T, Branscomb E, Predki P, Richardson P, Wenning S, Slezak T, Doggett N, Cheng JF, Olsen A, Lucas S, Elkin C, Uberbacher E, Frazier M, Gibbs RA, Muzny DM, Scherer SE, Bouck JB, Sodergren EJ, Worley KC, Rives CM, Gorrell JH, Metzker ML, Naylor SL, Kucherlapati RS, Nelson DL, Weinstock GM, Sakaki Y, Fujiyama A, Hattori M, Yada T, Toyoda A, Itoh T, Kawagoe C, Watanabe H, Totoki Y, Taylor T, Weissenbach J, Heilig R, Saurin W, Artiguenave F, Brottier P, Bruls T, Pelletier E, Robert C, Wincker P, Smith DR, Doucette-Stamm L, Rubenfield M, Weinstock K, Lee HM, Dubois J, Rosenthal A, Platzer M, Nyakatura G, Taudien S, Rump A, Yang H, Yu J, Wang J, Huang G, Gu J, Hood L, Rowen L, Madan A, Qin S, Davis RW, Federspiel NA, Abola AP, Proctor MJ, Myers RM, Schmutz J, Dickson M, Grimwood J, Cox DR, Olson MV, Kaul R, Raymond C, Shimizu N, Kawasaki K, Minoshima S, Evans GA, Athanasiou M, Schultz R, Roe BA, Chen F, Pan H, Ramser J, Lehrach H, Reinhardt R, McCombie WR, de la Bastide M, Dedhia N, Blöcker H, Hornischer K, Nordsiek G, Agarwala R, Aravind L, Bailey JA, Bateman A, Batzoglou S, Birney E, Bork P, Brown DG, Burge CB, Cerutti L, Chen HC, Church D, Clamp M, Copley RR, Doerks T, Eddy SR, Eichler EE, Furey TS, Galagan J, Gilbert JG, Harmon C, Hayashizaki Y, Haussler D, Hermjakob H, Hokamp K, Jang W, Johnson LS, Jones TA, Kasif S, Kaspryzk A, Kennedy S, Kent WJ, Kitts P, Koonin EV, Korf I, Kulp D, Lancet D, Lowe TM, McLysaght A, Mikkelsen T, Moran JV, Mulder N, Pollara VJ, Ponting CP, Schuler G, Schultz J, Slater G, Smit AF, Stupka E, Szustakowki J, Thierry-Mieg D, Thierry-Mieg J, Wagner L, Wallis J, Wheeler R, Williams A, Wolf YI, Wolfe KH, Yang SP, Yeh RF, Collins F, Guyer MS, Peterson J, Felsenfeld A, Wetterstrand KA, Patrinos A, Morgan MJ, de Jong P, Catanese JJ, Osoegawa K, Shizuya H, Choi S, Chen YJ, Szustakowki J; International Human Genome Sequencing Consortium. Initial sequencing and analysis of the human genome. Nature. 2001 Feb 15;409(6822):860-921. Erratum in: Nature 2001 Aug 2;412(6846):565. Nature 2001 Jun 7;411(6838):720. Szustakowki, J [corrected to Szustakowski, J].

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Responsible Party: National Institute of Neurological Disorders and Stroke (NINDS)
ClinicalTrials.gov Identifier: NCT00018889    
Other Study ID Numbers: 010206
01-N-0206
First Posted: July 9, 2001    Key Record Dates
Last Update Posted: December 30, 2021
Last Verified: December 22, 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) ):
Clinical Evaluation
Genetic Study
Essential Tremor
Familial Myoclonus
Hereditary Ataxia
Natural History
Movement Disorder
Inherited Movement Disorder
Additional relevant MeSH terms:
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Movement Disorders
Disease
Pathologic Processes
Central Nervous System Diseases
Nervous System Diseases