Study to Determine Mutations in the Gaucher Gene in Patients With Idiopathic Parkinson's Disease for Phenotype-genotype Correlation - Full Text View

Purpose

The genotype-phenotype correlation in patients with Parkinson's disease with specific mutations in the glucocerebrosidase gene (Gaucher gene) is known from own clinical experiences as well as from case reports in the literature. The epidemiological study will determine the frequency of heterozygous mutations in the glucocerebrosidase gene and correlate to the clinical onset and development by measuring and documenting severity of symptoms (e.g. cognitive deficits, L-dopa responsiveness, depression) in clinically well-characterized Parkinson's patients.

Condition
Parkinson Disease Idiopathic Parkinson Disease

Study Type:	Observational
Study Design:	Observational Model: Cohort Time Perspective: Prospective
Official Title:	Epidemiological Study to Determine Mutations in the Gaucher Gene in Patients With Idiopathic Parkinson's Disease for Phenotype-genotype Correlation

Resource links provided by NLM:

Genetics Home Reference related topics: Parkinson disease Perry syndrome

MedlinePlus related topics: Brain Diseases Degenerative Nerve Diseases Neurologic Diseases Parkinson's Disease

U.S. FDA Resources

Further study details as provided by University of Rostock:

Estimated Enrollment:	2100
Study Start Date:	January 2011
Estimated Study Completion Date:	December 2013
Estimated Primary Completion Date:	June 2013 (Final data collection date for primary outcome measure)

Groups/Cohorts
Observation all adult Patients at 18 years with a confirmed diagnosis of Parkinson's disease

Detailed Description:

Parkinson's disease (also known as Parkinson's, Parkinson disease, or PD) is a degenerative disorder of the central nervous system that impairs motor skills, cognitive processes, and other functions. The most obvious symptoms are motor-related, including tremor, rigidity, slowness of movement, and postural instability. Among non-motor symptoms are autonomic dysfunction and sensory and sleep difficulties. Cognitive and neurobehavioral problems, including dementia, are common in the advanced stages of the disease. PD usually appears around the age of 60, although there are young-onset cases.

Gaucher's disease is a genetic disease in which a fatty substance (lipid) accumulates in cells and certain organs. Gaucher's disease is the most common of the lysosomal storage diseases. It is caused by a hereditary deficiency of the enzyme glucocerebrosidase (also known as acid β-glucosidase). The enzyme acts on a fatty substance glucocerebroside (also known as glucosylceramide). When the enzyme is defective, glucocerebroside accumulates, particularly in white blood cells (mononuclear leukocytes). Glucocerebroside can collect in the spleen, liver, kidneys, lungs, brain and bone marrow.

Symptoms of Parkinson's syndrome in classical type 1 Gaucher patients were first systematically described in 1996. In GD patients, a marked heterogeneity is detected in terms of disease-causing mutations. In 17 Gaucher patients with symptoms of Parkinson's disease, 12 different genotypes were sequenced and compared to other Parkinson's patients, a lower L-dopa responsiveness, a higher frequency of cortical dysfunction and a relatively early onset of the symptoms was described. Many of these Gaucher patients with clinical Parkinson's symptoms had a positive family history of Parkinson's disease among relatives with heterozygous mutations in the Gaucher gene that could be confirmed in systematic studies.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No
Sampling Method:	Probability Sample

Study Population

adult patients with a confirmed diagnosis of Parkinson's disease

Criteria

Inclusion Criteria:

Male or female patients at 18 years old
Patients with confirmed diagnosis of Parkinson's disease
Signed informed consent

Exclusion Criteria:

Male or female patients being younger than 18 years old
Patients without confirmed diagnosis of Parkinson's disease
Missing signed informed consent

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01272687

Contacts

Contact: Arndt Rolfs, MD	49-381-494 ext 9540	arndt.rolfs@med.uni-rostock.de
Contact: Matthias Wittstock, MD	49-381-494 ext 4791	matthias.wittstock@med.uni-rostock.de

Locations

Germany
Fachkrankenhaus für neurologische Akut- und Rehabilitationsmedizin	Recruiting
Bad Neustadt, Germany, 97616
Contact: Matthias Hahne, MD +49 9771 ext 9080 m.hahne.akut@neurologie-bad-neustadt.de
Principal Investigator: Matthias Hahne, MD
Universitätsklinikum Dresden Klinik für Neurologie	Recruiting
Dresden, Germany, 01307
Contact: Alexander Storch, MD +49 351 458 ext 2532 Alexander.Storch@neuro.med.tu-dresden.de
Sub-Investigator: Mareike Fauser, MD
University of Giessen, Department of Neurology	Recruiting
Giessen, Germany, 35385
Contact: Christian Tanislav, MD +49 641 9854 ext 5372 christian.tanislav@neuro.med.uni-giessen.de
Sub-Investigator: Christian Tanislav, MD
Ernst-Moritz-Arndt-University of Greifswald, Department of Neurology	Recruiting
Greifswald, Germany, 17489
Contact: Christoph Kessler, MD +49 3834 ext 866800 Kessler@uni-greifswald.de
Principal Investigator: Christoph Kessler, MD
Universitätskrankenhaus Hamburg-Eppendorf, Department of Neurology	Recruiting
Hamburg, Germany, 20246
Contact: Alexander Münchau, MD +49 40 - 7410 ext 50134 muenchau@uke.uni-hamburg.de
Sub-Investigator: Simone Zittel, MD
Medizinische Hochschule Hannover, Bewegungsstörungsambulanz	Recruiting
Hannover, Germany, 30625
Contact: Gabriele Dierks +49 511 ext 5323670 Dierks.Gabriele@mh-hannover.de
Principal Investigator: Dirk Dressler, MD
Alexianer Krefeld GmbH, Krankenhaus Maria Hilf	Recruiting
Krefeld, Germany, 47805
Contact: Hans-Jürgen von Giesen, MD +49 2151 334 ext 7156 h-j.vgiesen@alexianer-krefeld.de
Principal Investigator: Hans-Jürgen von Giesen, MD
Gertrudis-Kliniken im Parkinson-Zentrum	Recruiting
Leun-Biskirchen, Germany, 35638
Contact: Ilona Csoti, MD +49 6473-3050 Parkinson-Center@t-online.de
Principal Investigator: Ilona Csoti, MD
Neurologischische Arztpraxis	Recruiting
Rostock, Germany, 18057
Contact: Liane Hauk-Westerhoff, MD +49 381 37555 ext 224 liane.hauk-westerhoff@nervenaerzte-rostock.de
Principal Investigator: Liane Hauk-Westerhoff, MD
Universitätsklinikum Rostock, Klinik für Neurologie	Recruiting
Rostock, Germany, 18147
Contact: Matthias Wittstock, MD +49 381 494 ext 4791 matthias.wittstock@med.uni-rostock.de
Sub-Investigator: Matthias Wittstock, MD
Klinikverbund Südwest, Klinikum Sindelfingen-Böblingen	Recruiting
Sindelfingen, Germany, 71085
Contact: Gay Arnold +49 7031 ext 982362 neurologie.si@klinikverbund-suedwest.de
Principal Investigator: Gay Arnold, MD
HANSE-Klinikum, Department of Neurology	Recruiting
Stralsund, Germany, 18410
Contact: Jörn Peter Sieb, MD +49 3831 352 ext 550 j.sieb@klinikum-hst.de
Sub-Investigator: Wael Marouf, MD
Sub-Investigator: Thomas Bocola, MD
University of Ulm, Department of Neurology	Recruiting
Ulm, Germany, 89081
Contact: Jan Kassubek, MD +49 731 177 ext 5210 jan.kassubek@uni-ulm.de
Principal Investigator: Jan Kassubek, MD
Stiftung Deutsche Klinik für Diagnostik GmbH Fachbereich Neurologie	Recruiting
Wiesbaden, Germany, 65191
Contact: Wolfgang Jost, MD +49 611 577 ext 652 jost.neuro@dkd-wiesbaden.de
Sub-Investigator: Natalie Hackert-Lust, MD
Thailand
Chulalongkorn University Hospital	Recruiting
Bangkok, Thailand, 10330
Contact: Bhidayasiri Roongroj, MD +662 256 ext 4627 rbh1@ucla.edu
Principal Investigator: Bhidayasiri Roongroj, MD

Sponsors and Collaborators

University of Rostock

Investigators

Principal Investigator:

Arndt Rolfs, MD

University of Rostock, Albrecht-Kossel-Institute for Neuroregeneration

More Information

Publications:

Bras J, Singleton A, Cookson MR, Hardy J. Emerging pathways in genetic Parkinson's disease: Potential role of ceramide metabolism in Lewy body disease. FEBS J. 2008 Dec;275(23):5767-73. Review.

Clark LN, Ross BM, Wang Y, Mejia-Santana H, Harris J, Louis ED, Cote LJ, Andrews H, Fahn S, Waters C, Ford B, Frucht S, Ottman R, Marder K. Mutations in the glucocerebrosidase gene are associated with early-onset Parkinson disease. Neurology. 2007 Sep 18;69(12):1270-7.

Gan-Or Z, Giladi N, Rozovski U, Shifrin C, Rosner S, Gurevich T, Bar-Shira A, Orr-Urtreger A. Genotype-phenotype correlations between GBA mutations and Parkinson disease risk and onset. Neurology. 2008 Jun 10;70(24):2277-83. Epub 2008 Apr 23.

Goker-Alpan O, Schiffmann R, LaMarca ME, Nussbaum RL, McInerney-Leo A, Sidransky E. Parkinsonism among Gaucher disease carriers. J Med Genet. 2004 Dec;41(12):937-40.

Kalinderi K, Bostantjopoulou S, Paisan-Ruiz C, Katsarou Z, Hardy J, Fidani L. Complete screening for glucocerebrosidase mutations in Parkinson disease patients from Greece. Neurosci Lett. 2009 Mar 13;452(2):87-9. Epub 2009 Jan 15.

Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, Yokochi M, Mizuno Y, Shimizu N. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature. 1998 Apr 9;392(6676):605-8.

Mitsui J, Mizuta I, Toyoda A, Ashida R, Takahashi Y, Goto J, Fukuda Y, Date H, Iwata A, Yamamoto M, Hattori N, Murata M, Toda T, Tsuji S. Mutations for Gaucher disease confer high susceptibility to Parkinson disease. Arch Neurol. 2009 May;66(5):571-6.

Neudorfer O, Giladi N, Elstein D, Abrahamov A, Turezkite T, Aghai E, Reches A, Bembi B, Zimran A. Occurrence of Parkinson's syndrome in type I Gaucher disease. QJM. 1996 Sep;89(9):691-4.

Neumann J, Bras J, Deas E, O'Sullivan SS, Parkkinen L, Lachmann RH, Li A, Holton J, Guerreiro R, Paudel R, Segarane B, Singleton A, Lees A, Hardy J, Houlden H, Revesz T, Wood NW. Glucocerebrosidase mutations in clinical and pathologically proven Parkinson's disease. Brain. 2009 Jul;132(Pt 7):1783-94. Epub 2009 Mar 13.

Nichols WC, Pankratz N, Marek DK, Pauciulo MW, Elsaesser VE, Halter CA, Rudolph A, Wojcieszek J, Pfeiffer RF, Foroud T; Parkinson Study Group-PROGENI Investigators. Mutations in GBA are associated with familial Parkinson disease susceptibility and age at onset. Neurology. 2009 Jan 27;72(4):310-6. Epub 2008 Nov 5.

Sidransky E. Gaucher disease: complexity in a "simple" disorder. Mol Genet Metab. 2004 Sep-Oct;83(1-2):6-15. Review.

Sidransky E, Nalls MA, Aasly JO, Aharon-Peretz J, Annesi G, Barbosa ER, Bar-Shira A, Berg D, Bras J, Brice A, Chen CM, Clark LN, Condroyer C, De Marco EV, Dürr A, Eblan MJ, Fahn S, Farrer MJ, Fung HC, Gan-Or Z, Gasser T, Gershoni-Baruch R, Giladi N, Griffith A, Gurevich T, Januario C, Kropp P, Lang AE, Lee-Chen GJ, Lesage S, Marder K, Mata IF, Mirelman A, Mitsui J, Mizuta I, Nicoletti G, Oliveira C, Ottman R, Orr-Urtreger A, Pereira LV, Quattrone A, Rogaeva E, Rolfs A, Rosenbaum H, Rozenberg R, Samii A, Samaddar T, Schulte C, Sharma M, Singleton A, Spitz M, Tan EK, Tayebi N, Toda T, Troiano AR, Tsuji S, Wittstock M, Wolfsberg TG, Wu YR, Zabetian CP, Zhao Y, Ziegler SG. Multicenter analysis of glucocerebrosidase mutations in Parkinson's disease. N Engl J Med. 2009 Oct 22;361(17):1651-61.

Tayebi N, Walker J, Stubblefield B, Orvisky E, LaMarca ME, Wong K, Rosenbaum H, Schiffmann R, Bembi B, Sidransky E. Gaucher disease with parkinsonian manifestations: does glucocerebrosidase deficiency contribute to a vulnerability to parkinsonism? Mol Genet Metab. 2003 Jun;79(2):104-9.

Responsible Party:	Prof. Dr. Arndt Rolfs, Prof. Dr. med., University of Rostock
ClinicalTrials.gov Identifier:	NCT01272687 History of Changes
Other Study ID Numbers:	PD02/2011
Study First Received:	January 7, 2011
Last Updated:	March 15, 2013
Health Authority:	Germany: Ethics Commission

Keywords provided by University of Rostock:

Parkinson Disease
Parkinsonian Disorders
Brain Diseases

Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases

Additional relevant MeSH terms:

Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases

Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases

ClinicalTrials.gov processed this record on May 23, 2013

Study to Determine Mutations in the Gaucher Gene in Patients With Idiopathic Parkinson's Disease for Phenotype-genotype Correlation (PadGau)