Parkinson DiseaseNCT03811496
Biomarker Analysis for GBA Associated Parkinson's Disease
An observational study of Parkinson Disease and Gaucher Disease, run by Lysosomal and Rare Disorders Research and Treatment Center, Inc. at 1 site in United States.
Trial summary
The primary aim of the study is to conclusively demonstrate the possibility of using the following molecules, α-Synuclein, LRRK2 and Parkin individually or in combination as biomarkers for Parkinson's disease (PD) progression in patients/ carriers of Gaucher disease (GD). Read more about this study
- Who is it for?
- Ages 50 years and olderHealthy volunteers can take part
- Conditions the study is for
- Parkinson Disease, Gaucher Disease
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Feb 2018to Jul 2020
- Phase
- Observational
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 50 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Study will include three cohorts: 1. Patients and carriers of Gaucher disease with confirmed mutations in GBA gene who have developed Parkinson's disease symptoms (GD-PD), 2. Patients with Gaucher disease but no known Parkinson's symptoms (GD-nonPD) and 3. Non-Gaucher disease/healthy controls (nonGD-nonPD). All participants will be recruited after obtaining informed consent using IRB (Independent Review Board) approved informed consent form.
Who may be able to join
- The study will include
- adult subjects age 21 or older with Gaucher disease with and without parkinsonism and individuals from families with a Gaucher proband and a history of parkinsonism.
- Controls will include unaffected siblings of patients with Gaucher disease and subjects with sporadic PD, without glucocerebrosidase mutations, and healthy volunteers who do not have a family history of parkinsonism or Gaucher disease.
Who cannot join
- Subjects excluded from the study include those who:
- present with severe cognitive deficits impairing decision making
- are unable to or for whom it is medically unsafe to withdraw from their current medications, such as subjects on SSRI s and other psychoactive drugs. The subjects on SSRIs may be included in the study only with an approval from the prescribing physician to discontinue their medications temporarily for the study.
- are pregnant or nursing. All women of child bearing potential will undergo a pregnancy test.
- have a history of neurologic conditions such as stroke or any focal brain lesion that may result in parkinonian manifestations. Individuals with such MRI findings will be excluded from the study.
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
LDRTC
Fairfax, Virginia, 22030
Renuka Limgala, PhD, 240-715-5382, rlimgala@ldrtc.org
Ozlem Goker-Alpan, MD
About this study
Official title: Biomarker Analysis for Parkinson's Disease in Subjects With Glucocerebrosidase Mutations
The primary aim of the study is to conclusively demonstrate the possibility of using the following molecules, α-Synuclein, LRRK2 and Parkin individually or in combination as biomarkers for Parkinson's disease (PD) progression in patients/ carriers of Gaucher disease (GD). All the assays will be performed only using peripheral blood, thus the identification of a peripheral marker that can be used in both diagnosis and prognosis of the disease and symptom severity would lead to a fast, efficient and reliable assay that can be performed on an easily accessible tissue type outside of the brain. It is now known that patients with GD, even carriers with one mutated GBA gene (OMIM 606463) are at a higher risk for developing PD, and at an earlier age. In an attempt to assess whether GBA alterations would also impact α-Synuclein and Parkin metabolism in humans, the expression at both molecular and protein level in the peripheral blood mononuclear cells (PBMCs) will be investigated.
Read the detailed description
The GBA (OMIM 606463) gene codes for beta-glucocerebrosidase, a lysosomal enzyme. Disease causing mutations in both alleles of GBA gene cause Gaucher disease (GD) while mutations in one allele lead to Gaucher carrier status. It has been shown recently that patients with GD, even carriers with one mutated GBA gene are at a higher risk for developing Parkinson disease (PD), and at an earlier age, and that the GBA mutations comprise the primary genetic risk factor in the development of PD and other forms of parkinsonism. However, there are no biomarkers to determine the diagnosis of PD, especially in the early and minimally symptomatic or asymptomatic stage. The progression of PD in subjects with a mutation in the GBA gene can currently not be determined. In some cellular and animal models, glucocerebrosidase alterations were shown to impact the metabolism of other proteins implicated in PD pathology. α-Synuclein and Parkin, encoded by SNCA and PARK2 respectively, are implicated in rare genetic forms of parkinsonism. α-Synuclein aggregates are seen in cells of the central and peripheral nervous system and is considered to be the pathological culprit in PD. Mutated glucocerebrosidase has been shown to be present in α-Synuclein aggregates in postmortem brain samples from individuals with GBA mutations and PD. α-Synuclein in addition, is shown to affect the solubility of Parkin in the cells. As an attempt to assess whether GBA alterations would also impact α-Synuclein and Parkin metabolism in humans in easily accessible cell types outside the brain, the expression at both molecular and protein level will be investigated in the peripheral blood mononuclear cells (PBMCs). The study includes three cohorts: 1) Patients and carriers of Gaucher disease with confirmed disease causing mutations in GBA gene who have developed Parkinson's disease symptoms (GD-PD), 2) Patients and carriers of Gaucher disease with no known Parkinson's symptoms (GD-nonPD) and 3) Non-Gaucher disease/healthy controls (HC). PBMCs extracted from 3-5 ml peripheral blood will be used for intracellular staining for α-Synuclein, LRRK2 and Parkin and then acquired on Flow cytometer (BD accuri). Lymphocytes and monocytes will be analyzed for α-Synuclein, LRRK2 and Parkin expression. PBMCs will also be used for RNA extraction and subsequent molecular analysis using qPCR. Since the assay utilizes an easily accessible tissue type i.e., peripheral blood and requires a very small amount (2-3 ml), this assay could be developed as a potential biomarker for diagnosis and a disease progression indicator for Parkinson disease in subjects with GBA gene mutations.
- Conditions
- Parkinson Disease, Gaucher Disease
- Keywords
- Parkinson disease, Gaucher disease, GBA gene, alpha-synuclein
- Medical subject headings
- Parkinson Disease, Gaucher Disease, Parkinson Disease 4, Autosomal Dominant Lewy Body
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| GD-PD | Patients and carriers of Gaucher disease with confirmed mutations in GBA gene who have developed Parkinson's disease symptoms | |
| GD-nonPD | Patients with Gaucher disease but no known Parkinson's symptoms | |
| nonGD-nonPD | Non-Gaucher disease/healthy controls |
What is being measured
The primary outcome is the main question the study is designed to answer.
Gene expression levels of SNCA
Gene expression levels relative to internal reference genes will be compared between the individual subjects as well as grouped analysis to identify a specific pattern in alterations in level of expression of SNCA.
Measured: 18 months
Gene expression levels of LRRK2
Gene expression levels relative to internal reference genes will be compared between the individual subjects as well as grouped analysis to identify a specific pattern in alterations in level of expression of LRRK2.
Measured: 18 months
Gene expression levels of Parkin
Gene expression levels relative to internal reference genes will be compared between the individual subjects as well as grouped analysis to identify a specific pattern in alterations in level of expression of Parkin.
Measured: 18 months
Protein expression levels of alpha-synuclein
Protein expression levels of alpha-synuclein will be analyzed using flow cytometry and compared between the individual subjects as well as grouped analysis to identify a specific pattern in alterations in level of expression.
Measured: 18 months
Protein expression levels of LRRK2
Protein expression levels of LRRK2 will be analyzed using flow cytometry and compared between the individual subjects as well as grouped analysis to identify a specific pattern in alterations in level of expression.
Measured: 18 months
Protein expression levels of Parkin
Protein expression levels of Parkin will be analyzed using flow cytometry and compared between the individual subjects as well as grouped analysis to identify a specific pattern in alterations in level of expression.
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2019
- Study start1 Feb 2018
- Primary completionFeb 2020 (estimated)
- Study completionJul 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Parkinson DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Lysosomal and Rare Disorders Research and Treatment Center, Inc.
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ozlem Goker-Alpan, MD, Principal investigator, LDRTCRenuka Limgala, PhD, Principal investigator, LDRTC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03811496
- Sponsor's protocol ID
- 18-LDRTC-01
- Status last verified
- Jan 2019
- First submitted
- 18 Jan 2019
- Last updated
- 23 Jan 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided