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Parkinson's DiseaseNCT04228172

Genotypic Influences on Network Progression in Parkinson's Disease

An observational study of Parkinson's Disease, run by Northwell Health at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

In this longitudinal study, the investigators will follow Parkinson's disease (PD) patients with and without glucocerebrosidase (GBA) mutations. The investigators hypothesize that the rate of increase in brain network activity over time (network progression rate) is faster in patients with GBA gene mutations. Read more about this study

Who is it for?
Ages 40 to 75 years
Conditions the study is for
Parkinson's Disease
What is being tested?
DNA/GeneticTesting, FDG PET scan and MRI scan
Type of treatment
Surgery or procedure
How many people
17 participants
Where
1 siteUnited States
Study dates
24 Feb 2020to 7 Mar 2026
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 40 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Study population: Study population will be recruited through local movement disorders centers in the tri-state area, prior PD studies, The Michael J. Fox Trial Finder, community outreach

Who may be able to join

  • Diagnosis of PD made according to United Kingdom (UK) Parkinson's Disease Society Brain Bank Criteria
  • Ability to provide written informed consent
  • Age 40-75
  • Stable dose of antiparkinsonian medication for >1 month prior to study entry

Who cannot join

  • Subjects with pathogenic mutations in LRRK2 related PD mutations (subjects with variants of uncertain significance (VUS) are eligible
  • History of known causative factors such as encephalitis or neuroleptic treatment
  • Patients with dementia (defined as Mini-Mental Status Exam score <24 or a Telephone Interview for Cognitive Status score <26)
  • Atypical parkinsonian features including oculomotor abnormalities, incontinence, ataxia, sensory loss, or pyramidal signs
  • Known structural brain lesions
  • Patients with history of stroke, head injury, high intracranial pressure or severe headaches
  • Psychiatric disorder, including a history of major depression in the past 36 months
  • Pregnant or breastfeeding women (female subjects of child-bearing potential will be screened for pregnancy before imaging).

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Feinstein Institutes for Medical Research

    Manhasset, New York, 11030

Other trials in United States

About this study

In this longitudinal study, the investigators will follow Parkinson's disease (PD) patients with and without glucocerebrosidase (GBA) mutations. The investigators hypothesize that the rate of increase in brain network activity over time (network progression rate) is faster in patients with GBA gene mutations.

Read the detailed description

Parkinson's disease (PD) patients with mutations in the glucocerebrosidase gene (GBA) tend to have a more aggressive disease course. GBA may therefore provide a target for disease modifying therapies in mutation carriers. Using positron emission tomography (PET) and magnetic resonance imaging (MRI) brain imaging to measure network progression rates in mutation carriers will allow for the assessment of the potential disease modifying effects of new anti-GBA therapies.

The investigators will also determine whether magnetic resonance imaging (MRI) network methods, which are less invasive and more broadly available than positron emission tomography (PET), produce comparable network progression measurements in individual patients. These determinations will be critical for the design of clinical trials of new disease-modifying drugs.

Being tested
DNA/GeneticTesting, FDG PET scan, MRI scan, Clinical and neuropsychological assessments
Keywords
GBA, genetic, progression, PD, glucocerebrosidase
Medical subject headings
Parkinson Disease, Disease Progression

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DNA/GeneticTestingGenetic

    Subjects will be tested for GBA and LRRK2 mutation status at baseline.

  • FDG PET scanRadiation

    18F-Fluoro-2-deoxy-glucose (FDG) PET scan is a nuclear medicine test that measures glucose metabolism (energy) in your brain at baseline and 18 months later.

  • MRI scanOther

    Magnetic Resonance Imaging (MRI) is a noninvasive scan which produces detailed pictures of the brain using a magnetic field. In addition, a special type of MRI, called resting state functional MRI (rs-fMRI), will measure and map brain activity. Conducted at baseline and 18 months later.

  • Clinical and neuropsychological assessmentsOther

    Investigator will evaluate subjects according to the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), the standard clinical tool used to measure the severity and progression of PD. Neuropsychological evaluation will assess how one's brain functions (via pencil and paper testing), which indirectly yields information about the structural and functional integrity of the brain. Conducted at baseline and 18 months later.

Study groups in NCT04228172
Study groupRoleWhat they receive
Parkinson's disease (PD) glucocerebrosidase (GBA) carriersParkinson's disease subjects with GBA mutation
Receives: Genetic: DNA/GeneticTesting; Radiation: FDG PET scan; Other: MRI scan; Other: Clinical and neuropsychological assessments
Parkinson's disease (PD) non glucocerebrosidase (GBA) carriersParkinson's disease subjects without GBA mutation
Receives: Genetic: DNA/GeneticTesting; Radiation: FDG PET scan; Other: MRI scan; Other: Clinical and neuropsychological assessments

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Increase in PD related metabolic pattern expression

    Changes in PD related and PD cognition related pattern expression in 18F-2-fluoro-2-deoxy-D-glucose (FDG) PET scans

    Measured: Baseline and 18 months later

  2. Increase in PD related functional pattern expression

    Changes in PD related and PD cognition related pattern expression in resting state functional magnetic resonance imaging (rs-fMRI)

    Measured: Baseline and 18 months later

Secondary outcomes (2)

  1. Change in motor function

    Change in motor function assessed with Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III (The sum score ranges between 0-132 points. Higher scores indicate more severe impairment)

    Measured: Baseline and 18 months later

  2. Change in cognitive function

    Change in cognitive function assessed with neuropsychological testing

    Measured: Baseline and 18 months later

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Jan 2020
  2. Study start24 Feb 2020
  3. Primary completion7 Mar 2026
  4. Study completion7 Mar 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Case-control
Time perspective
Prospective
Enrolment
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04228172
Sponsor's protocol ID
MJFF grant 16325
Status last verified
Oct 2026
First submitted
7 Jan 2020
Last updated
3 Nov 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Davis MY, Johnson CO, Leverenz JB, Weintraub D, Trojanowski JQ, Chen-Plotkin A, Van Deerlin VM, Quinn JF, Chung KA, Peterson-Hiller AL, Rosenthal LS, Dawson TM, Albert MS, Goldman JG, Stebbins GT, Bernard B, Wszolek ZK, Ross OA, Dickson DW, Eidelberg D, Mattis PJ, Niethammer M, Yearout D, Hu SC, Cholerton BA, Smith M, Mata IF, Montine TJ, Edwards KL, Zabetian CP. Association of GBA Mutations and the E326K Polymorphism With Motor and Cognitive Progression in Parkinson Disease. JAMA Neurol. 2016 Oct 1;73(10):1217-1224. doi: 10.1001/jamaneurol.2016.2245.

    PubMed 27571329

  • Cilia R, Tunesi S, Marotta G, Cereda E, Siri C, Tesei S, Zecchinelli AL, Canesi M, Mariani CB, Meucci N, Sacilotto G, Zini M, Barichella M, Magnani C, Duga S, Asselta R, Solda G, Seresini A, Seia M, Pezzoli G, Goldwurm S. Survival and dementia in GBA-associated Parkinson's disease: The mutation matters. Ann Neurol. 2016 Nov;80(5):662-673. doi: 10.1002/ana.24777. Epub 2016 Oct 3.

    PubMed 27632223

  • Sidransky E, Lopez G. The link between the GBA gene and parkinsonism. Lancet Neurol. 2012 Nov;11(11):986-98. doi: 10.1016/S1474-4422(12)70190-4.

    PubMed 23079555

  • Schindlbeck KA, Eidelberg D. Network imaging biomarkers: insights and clinical applications in Parkinson's disease. Lancet Neurol. 2018 Jul;17(7):629-640. doi: 10.1016/S1474-4422(18)30169-8.

    PubMed 29914708

  • 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. doi: 10.1093/brain/awp044. Epub 2009 Mar 13.

    PubMed 19286695

  • Winder-Rhodes SE, Evans JR, Ban M, Mason SL, Williams-Gray CH, Foltynie T, Duran R, Mencacci NE, Sawcer SJ, Barker RA. Glucocerebrosidase mutations influence the natural history of Parkinson's disease in a community-based incident cohort. Brain. 2013 Feb;136(Pt 2):392-9. doi: 10.1093/brain/aws318.

    PubMed 23413260

  • Alcalay RN, Levy OA, Waters CC, Fahn S, Ford B, Kuo SH, Mazzoni P, Pauciulo MW, Nichols WC, Gan-Or Z, Rouleau GA, Chung WK, Wolf P, Oliva P, Keutzer J, Marder K, Zhang X. Glucocerebrosidase activity in Parkinson's disease with and without GBA mutations. Brain. 2015 Sep;138(Pt 9):2648-58. doi: 10.1093/brain/awv179. Epub 2015 Jun 27.

    PubMed 26117366

  • Mazzulli JR, Xu YH, Sun Y, Knight AL, McLean PJ, Caldwell GA, Sidransky E, Grabowski GA, Krainc D. Gaucher disease glucocerebrosidase and alpha-synuclein form a bidirectional pathogenic loop in synucleinopathies. Cell. 2011 Jul 8;146(1):37-52. doi: 10.1016/j.cell.2011.06.001. Epub 2011 Jun 23.

    PubMed 21700325

  • McNeill A, Magalhaes J, Shen C, Chau KY, Hughes D, Mehta A, Foltynie T, Cooper JM, Abramov AY, Gegg M, Schapira AH. Ambroxol improves lysosomal biochemistry in glucocerebrosidase mutation-linked Parkinson disease cells. Brain. 2014 May;137(Pt 5):1481-95. doi: 10.1093/brain/awu020. Epub 2014 Feb 25.

    PubMed 24574503

  • Sardi SP, Clarke J, Viel C, Chan M, Tamsett TJ, Treleaven CM, Bu J, Sweet L, Passini MA, Dodge JC, Yu WH, Sidman RL, Cheng SH, Shihabuddin LS. Augmenting CNS glucocerebrosidase activity as a therapeutic strategy for parkinsonism and other Gaucher-related synucleinopathies. Proc Natl Acad Sci U S A. 2013 Feb 26;110(9):3537-42. doi: 10.1073/pnas.1220464110. Epub 2013 Jan 7.

    PubMed 23297226

  • Feigin A, Kaplitt MG, Tang C, Lin T, Mattis P, Dhawan V, During MJ, Eidelberg D. Modulation of metabolic brain networks after subthalamic gene therapy for Parkinson's disease. Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19559-64. doi: 10.1073/pnas.0706006104. Epub 2007 Nov 27.

    PubMed 18042721

  • Niethammer M, Eidelberg D. Metabolic brain networks in translational neurology: concepts and applications. Ann Neurol. 2012 Nov;72(5):635-47. doi: 10.1002/ana.23631. Epub 2012 Aug 31.

    PubMed 22941893

  • Eidelberg D. Metabolic brain networks in neurodegenerative disorders: a functional imaging approach. Trends Neurosci. 2009 Oct;32(10):548-57. doi: 10.1016/j.tins.2009.06.003. Epub 2009 Sep 16.

    PubMed 19765835

  • Vo A, Sako W, Fujita K, Peng S, Mattis PJ, Skidmore FM, Ma Y, Ulug AM, Eidelberg D. Parkinson's disease-related network topographies characterized with resting state functional MRI. Hum Brain Mapp. 2017 Feb;38(2):617-630. doi: 10.1002/hbm.23260. Epub 2016 May 21.

    PubMed 27207613

  • Schindlbeck, K.A. et al., Multicenter validation of disease-related Parkinson's disease pattern with resting state fMRI. 21st International Congress of Parkinson's Disease and Movement Disorders, June 8, 2018, Vancouver, Canada

Questions about this trial

What is this clinical trial studying?

An observational study of Parkinson's Disease, run by Northwell Health at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Increase in PD related metabolic pattern expression (time frame: Baseline and 18 months later). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04228172, which also lists 22 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Nov 2026.

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