Non Motor Symptoms in Glucocerebrosidase-related Parkinson's Disease

NCT06451419 | Enrolling By Invitation

• 1 other identifier: 5564
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this observational study is to describe non motor symptoms in a prospective study of patients with Parkinson's disease associated to glucocerebrosidase (GBA-PD) mutations. The main questions it aims to answer are:

• Do GBA-PD patients have a greater burden of non motor symptoms?
• How do these non motor symptoms evolve during a prospective follow up of two years?
• Are these non motor symptoms different from those that affect Parkinson's disease patients without glucocerebrosidase mutations (non GBA-PD), in prevalence, severity and type?
• Do these non motor symptoms correlate with objective measures such as posturography or speed reaction tests?
• Is there a test or combination of tests that can predict the appearance of early or severe non motor symptoms? For this reason researchers will compare the GBA-PD group of patients with a group of non mutated GBA Parkinson disease. Participants will undergo a neurological and neuropsychological evaluation with different tests in subsequent visits for a total of 2 years.

Conditions

Parkinson Disease

Keywords

glucocerebrosidase heterozygous mutation; non motor symptoms; neuropsychology; posturography

Outcome Measures

Primary Outcomes (5)

• Change in non motor symptoms scale from baseline to 2 years

  To determine the non motor symptoms profile and its evolution through non motor symptoms scale in glucocerebrosidase mutated Parkinson's disease in comparison with those without mutations. 30 items with total scores from 0 to 360, higher scores meaning higher non motor symptoms burden.

  2 years

• Change in non motor symptoms scale from baseline to 6 months

  To determine the non motor symptoms profile and its evolution through non motor symptoms scale in glucocerebrosidase mutated Parkinson's disease in comparison with those without mutations. 30 items with total scores from 0 to 360, higher scores meaning higher non motor symptoms burden.

  6 months

• Change in non motor symptoms scale from 6 months to 1 year

  To determine the non motor symptoms profile and its evolution through non motor symptoms scale in glucocerebrosidase mutated Parkinson's disease in comparison with those without mutations. 30 items with total scores from 0 to 360, higher scores meaning higher non motor symptoms burden.

  6 months

• Change in non motor symptoms scale from 12 months to 18 months

  To determine the non motor symptoms profile and its evolution through non motor symptoms scale in glucocerebrosidase mutated Parkinson's disease in comparison with those without mutations. 30 items with total scores from 0 to 360, higher scores meaning higher non motor symptoms burden.

  6 months

• Change in non motor symptoms scale from 18 months to 24 months

  To determine the non motor symptoms profile and its evolution through non motor symptoms scale in glucocerebrosidase mutated Parkinson's disease in comparison with those without mutations. 30 items with total scores from 0 to 360, higher scores meaning higher non motor symptoms burden.

  6 months

Secondary Outcomes (130)

• Change in Montreal Cognitive Assessment scale from baseline to 2 years

  2 years

• Change in Montreal Cognitive Assessment scale from baseline to 6 months

  6 months

• Change in Montreal Cognitive Assessment scale from 6 months to 12 months

  6 months

• Change in Montreal Cognitive Assessment scale from12 months to 18 months

  6 months

• Change in Montreal Cognitive Assessment scale from18 months to 24 months

  6 months

Study Arms (2)

Glucocerebrosidase associated Parkinson's disease

Patients aged under 70 when symptoms began or with family history of Parkinson's disease who underwent a genetic testing including a pannel of 64 genes associated with Parkinson's diasease and who tested positive for heterozygous glucocerebrosidase mutation.

Other: Tests on non motor symptoms

Non glucocerebrosidase associated Parkinson's diasease

Patients aged under 70 when symptoms began or with family history of Parkinson's disease who underwent a genetic testing including a pannel of 64 genes associated with Parkinson's diasease and who tested negative for all the mutations in the pannel.

Other: Tests on non motor symptoms

Interventions

Tests on non motor symptoms OTHER

Neurological, neuropsychological and self-administered tests on non motor symptoms, including posturography and speed reaction times.

Glucocerebrosidase associated Parkinson's disease; Non glucocerebrosidase associated Parkinson's diasease

Eligibility Criteria

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

Study Population

Parkinson's disease patients whose symptoms began before they were 70 and/or those who had Parkinson's disease family history and underwent a genetic test including the following Parkinson's disease related genes: ADCY5, ANO, APOE, APP, ATP1A3, ATP9A, C19orf12, CHCHD2, CNEP1R1, COX20, CTDNEP1, DCTN1, DNAJC13, DNAJC6, ELOVO7, FJ47, FBXO7, GAK, GBA, GCDH, GCH1, GNAL, GNE, GRN, HPCA, KCTD17, KMT2B, LPIN1, LPIN2, LPIN3, LRRK2, MAPT, MCCC1, MCOLN1, NPC1, PANK2, PARK7, PDE8B, PDGFB PIN, PDGFR, PDGFR PLA2G, POLG, PRRKN, PRRKA, PSEN1, PSEN2, RAB12, RAB39B, SGCE excepto exón NM\_001099401 exón 10, SLC19A3, SLC20A2, SLC30A10, SLC39A14, SLC6A3, SNCA, SNCB, SYN-1, SYNJ1, TA, TH1 TOR1A, VAC14, VPS13C (hotspot exones 11, 3, 4, 61 y 9), VPS35, XPR1 and agreed to participate in the study.

You may qualify if:

• Aged over 18 years old.
• Fulfill Parkinson's disease criteria of Movement Disorder Society 2015.
• Parkinson's disease symptoms began before they were 70 and/or Parkinson's disease family history.
• Underwent a genetic test of Parkinson's disease related genes.
• Heterozygous mutation of glucocerebrosidase gene (only cases).
• Absence of mutation in the Parkinson's disease genetic test (only controls).

You may not qualify if:

• Suspicion of atypical parkinsonism.
• Personal history of other neurodegenerative disorders such as Alzheimer's disease.
• Personal history of significant cerebrovascular damage, intracraneal lessions or important craneoencephalic trauma.
• Deep brain stimulation treatment for Parkinson's disease.
• Moderate or severe dementia that precludes from performing the tests.

Sponsors & Collaborators

• Juan Pablo Romero. MD, PhD: lead
• Fundación de Investigación Biomédica - Hospital Universitario de La Princesa: collaborator

Study Sites (2)

Universidad Francisco de Vitoria

Pozuelo de Alarcón, Madrid, 28223, Spain

Location

Hospital Universitario La Princesa

Madrid, 28006, Spain

Location

Related Publications (7)

• 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, Durr 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. doi: 10.1056/NEJMoa0901281.

  PMID: 19846850 RESULT

• Barkhuizen M, Anderson DG, Grobler AF. Advances in GBA-associated Parkinson's disease--Pathology, presentation and therapies. Neurochem Int. 2016 Feb;93:6-25. doi: 10.1016/j.neuint.2015.12.004. Epub 2015 Dec 30.

  PMID: 26743617 RESULT

• Brockmann K, Srulijes K, Pflederer S, Hauser AK, Schulte C, Maetzler W, Gasser T, Berg D. GBA-associated Parkinson's disease: reduced survival and more rapid progression in a prospective longitudinal study. Mov Disord. 2015 Mar;30(3):407-11. doi: 10.1002/mds.26071. Epub 2014 Dec 1.

  PMID: 25448271 RESULT

• Leocadi M, Canu E, Donzuso G, Stojkovic T, Basaia S, Kresojevic N, Stankovic I, Sarasso E, Piramide N, Tomic A, Markovic V, Petrovic I, Stefanova E, Kostic VS, Filippi M, Agosta F. Longitudinal clinical, cognitive, and neuroanatomical changes over 5 years in GBA-positive Parkinson's disease patients. J Neurol. 2022 Mar;269(3):1485-1500. doi: 10.1007/s00415-021-10713-4. Epub 2021 Jul 23.

  PMID: 34297177 RESULT

• Swan M, Doan N, Ortega RA, Barrett M, Nichols W, Ozelius L, Soto-Valencia J, Boschung S, Deik A, Sarva H, Cabassa J, Johannes B, Raymond D, Marder K, Giladi N, Miravite J, Severt W, Sachdev R, Shanker V, Bressman S, Saunders-Pullman R. Neuropsychiatric characteristics of GBA-associated Parkinson disease. J Neurol Sci. 2016 Nov 15;370:63-69. doi: 10.1016/j.jns.2016.08.059. Epub 2016 Aug 30.

  PMID: 27772789 RESULT

• Malek N, Weil RS, Bresner C, Lawton MA, Grosset KA, Tan M, Bajaj N, Barker RA, Burn DJ, Foltynie T, Hardy J, Wood NW, Ben-Shlomo Y, Williams NW, Grosset DG, Morris HR; PRoBaND clinical consortium. Features of GBA-associated Parkinson's disease at presentation in the UK Tracking Parkinson's study. J Neurol Neurosurg Psychiatry. 2018 Jul;89(7):702-709. doi: 10.1136/jnnp-2017-317348. Epub 2018 Jan 29.

  PMID: 29378790 RESULT

• Ren J, Zhou G, Wang Y, Zhang R, Guo Z, Zhou H, Zheng H, Sun Y, Ma C, Lu M, Liu W. Association of GBA genotype with motor and cognitive decline in Chinese Parkinson's disease patients. Front Aging Neurosci. 2023 Feb 10;15:1091919. doi: 10.3389/fnagi.2023.1091919. eCollection 2023.

  PMID: 36845659 RESULT

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Inés Muro, MD

  Hospital Universitario La Princesa

  PRINCIPAL INVESTIGATOR

• Juan P Romero, PhD

  Universidad Francisco de Vitoria

  STUDY DIRECTOR

• Lydia López, MD

  Hospital Universitario La Princesa

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical professor

Study Record Dates

• First Submitted: May 21, 2024
• First Posted: June 11, 2024
• Study Start: July 1, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): August 31, 2026
• Last Updated: June 28, 2024

Record last verified: 2024-06

Locations

ES (2)