Prodromal Parkinsonian Features in GBA1 Mutation Carriers

Objective of the trial. To define a sub-population which is at increased risk of developing Parkinson, beyond the fact of carrying Gaucher; in this sub-population the investigators shall conduct a comprehensive evaluation that includes a variety of non-invasive tests, whose purpose is to evaluate the state of the pre- Parkinson's disease signs, signs which can appear, even twenty years before the appearance of the disease, and also to compare them to a group of diagnosed Gaucher patients and a group of healthy people who are not carriers of Gaucher disease.

A group of those carriers will be available for trial or for treatment, if there will be a medicine for the prevention of the development of Parkinson, obtainable.

Study Overview

• Status: Recruiting
• Conditions: Healthy; Gaucher Disease, Type 1
• Intervention / Treatment: Diagnostic test: The investigators aim to identify prodromal PD in a cohort of carriers of Gaucher disease.

Detailed Description

The carriers, the healthy people and the Gaucher patients will undergo a number of non-invasive tests, which test the pre-Parkinson signs.

The tests are based on various sense tests, blood tests, measuring of blood pressure, lying and standing, ultra-sound of the brain and a neurological test (test of the nervous system and various questionnaires).

• Study Type: Observational
• Enrollment (Estimated): 600

Contacts and Locations

• Study Contact: Name: Ari Zimran, MD; Phone Number: +972-509149149; Email: azimran@gmail.com
• Study Contact Backup: Name: Michal Becker- Cohen, M.Sc.; Phone Number: +972-504606310; Email: michalbec@gmail.com

Study Locations

• Israel
  • Please Select...
    • Jerusalem, Please Select..., Israel, 9103102
      • Recruiting
      • Michal Becker- Cohen
      • Contact: Michal Becker- Cohen, M.Sc.; Phone Number: +97226555143; Email: michalbec@gmail.com
      • Contact: Ari Zimran, M.D.; Phone Number: +97226555143; Email: azimran@gmail.com
      • Principal Investigator: Ari Zimran, Prof.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Carriers of Gaucher disease mutation Gaucher patients Healthy controls

Description

Inclusion Criteria:

• Willing to participate

Exclusion Criteria:

• PD patients
• Dementia

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Carriers of Gaucher disease; Family of patients with Gaucher disease, sequenced for the GBA1 gene.	Diagnostic test: The investigators aim to identify prodromal PD in a cohort of carriers of Gaucher disease.; Tests to help identify prodromal PD in a cohort of carriers of Gaucher disease
Gaucher patients; Patients from the Gaucher clinic in Shaare Zedek Medical Center, Jerusalem, Israel	Diagnostic test: The investigators aim to identify prodromal PD in a cohort of carriers of Gaucher disease.; Tests to help identify prodromal PD in a cohort of carriers of Gaucher disease
Healthy controls; Family members of Gaucher patients who are not carriers of Gaucher disease	Diagnostic test: The investigators aim to identify prodromal PD in a cohort of carriers of Gaucher disease.; Tests to help identify prodromal PD in a cohort of carriers of Gaucher disease

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Building a model to identify carriers of Gaucher disease prone to Parkinson's disease, using tests to assess different domains of PD, including anatomy, cognitive and mental, sleep disorder, and motor.	Carriers of a variant in the GBA1 gene (GBA carriers) are at the highest risk of developing Parkinson disease (PD). A screening study for prodromal PD features in a cohort of obligatory GBA carriers between 40-75 years was initiated to identify candidates for a PD prevention trial. We added healthy controls and GD patients in order to determine the incidence of prodromal PD and for analyzing the differences between the two groups helping to build a model for identifying at risk PD at the prodromal stage. Participants preform 15 pre-defined non-invasive tests for prodromal PD and assessment of risk factors. Risk factors for PD included age, sex, type of GBA1 variant, coffee and tea caffeine consumption, smoking habits, exposure to solvents and pesticides, and family history of PD (1st and/or 2nd degree relatives with PD).	8 Years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Transcranial sonography (TCS)	Transcranial sonography (TCS) is a useful noninvasive diagnostic tool to detect hyperechogenicity (SN+) of the substantia nigra area in the brain. The hyperechogenicity happens due to increased amounts of iron, reflecting a functional impairment.	8 years
Color discrimination test	Color discrimination was analyzed using The Farnsworth-Munsell 100 hue test. The test includes four boxes with a fixed number of color shade caps with slight shade differences needed to be ordered correctly. The result of each box was entered into a computerized system and automated the total error score (TES)	8 years
Hyposmia by the Bit-A UPSIT smell test	The shorter version of the UPSIT smell test (The University of Pennsylvania Smell Identification Test) was used to evaluate hyposmia using twelve cards, each with a different smell.	8 years
Orthostatic hypotension (OH)	defined as a fall of at least 20 mmHg systolic or at least ten mmHg diastolic blood pressure by 3 min of active standing or head-up tilt	8 years
Montreal Cognitive Assessment (MoCA)	evaluate the cognitive and mental aspects associated with PD. A Montreal Cognitive Assessment (MoCA) score of 26 and above was considered normal	8 years
NeuroTrax computerized battery.	The NeuroTrax computerized battery (www.neurotrax.com) includes seven sections: memory, executive function, attention, information processing speed, visual-spatial, verbal function, and motor skills	8 years
Beck Depression Inventory	self-administered questioner including 21 questions used to screen, diagnose, and measure the severity of depression.	8 years
Frontal lobe assessment battery (FAB).	evaluates executive dysfunction	8 years
rapid eye movement (REM)	Idiopathic rapid eye movement sleep behavior disorder is an important risk factor in the diagnosis of PD. The REM questionnaire was completed by the participant.	8 years
Epworth sleepiness scale (ESS)	assessing daytime sleepiness includes an eight-question questionnaire scoring between 0 and 24; the higher the score, the higher the chances of dosing off	8 years
Perdue pegboard.	Perdue pegboard measures the movement of fingers, hands, and arms in 4 different tasks, testing motor abilities and coordination by placing as many pegs and discs on a board in three 30 seconds trials for each subset and three 60 second trials for the assembly subset	8 years
UPDRS part III.	measures gross motor function. A score above 6, not including postural and action tremor, was considered abnormal	8 years
The Timed Up and Go (iTUG).	The Timed Up and Go (iTUG) (EncephaLogTM) is a platform that utilizes smartphones' internal motion sensors for conducting motor evaluation including general walking score, step to step persistency, hand sway and rotation time.	8 years
Questionnaire regarding risk factors	Spontaneous bowel movement frequency was used to define constipation. Urinary and erectile dysfunction were assessed according to the MDS criteria	8 years

Collaborators and Investigators

• Sponsor: Shaare Zedek Medical Center
• Investigators: Principal Investigator: Ari Zimran, MD, Shaare Zedek Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): May 16, 2017
• Primary Completion (Estimated): January 16, 2030
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: November 11, 2021
• First Submitted That Met QC Criteria: February 21, 2022
• First Posted (Actual): February 24, 2022

Study Record Updates

• Last Update Posted (Actual): April 29, 2026
• Last Update Submitted That Met QC Criteria: April 23, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Lipid Metabolism Disorders; Lysosomal Storage Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases, Nervous System; Sphingolipidoses; Lipidoses; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Gaucher Disease
• Other Study ID Numbers: SZMC-0168-17

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED