Parkinson Disease
Conditions
Brief summary
The Leucine-Rich Repeat Kinase 2 (LRRK2) is implicated in autosomal dominant Parkinson's disease (PKD). An inhibitor for the leucine-rich repeat kinase 2 (LRRK2) is in pre-clinical development for potential use in treating Parkinson's disease. Patients with PKD have cognitive impairments which develop alongside the typical motor symptoms but a full characterisation of the neurocognitive phenotype of PKD patients with LRRK2 mutation is currently lacking. This observational study conducted on a single visit will assess the phenotypic neurocognitive abnormalities of PKD patients with the LRRK2 mutation with the aim of identifying potential PD endpoints related to the LRRK2 mutation for future Phase I or II clinical trials of LRRK2 inhibitors.
Detailed description
The Leucine-Rich Repeat Kinase 2 (LRRK2) is implicated in autosomal dominant Parkinson's disease (PKD). An inhibitor for the leucine-rich repeat kinase 2 (LRRK2) is in pre-clinical development for potential use in treating Parkinson's disease. Patients with PKD have cognitive impairments which develop alongside the typical motor symptoms but a full characterisation of the neurocognitive phenotype of PKD patients with LRRK2 mutation is currently lacking. This observational study conducted on a single visit will assess the phenotypic neurocognitive abnormalities of PKD patients with the LRRK2 mutation with the aim of identifying potential PD endpoints related to the LRRK2 mutation for future Phase I or II clinical trials of LRRK2 inhibitors. Approximately 20 subjects with PKD bearing one of the known LRRK2 mutations will be investigated. Approximately 20 healthy subjects without the LRRK2 mutation who are matched with PKD patients will also be evaluated. Healthy subjects are not expected to be taking medications for PKD. Subjects with PKD may continue their medications for PKD treatment throughout the study, Testing will take place within 30 days of screening, depending on the subject's availability.
Interventions
GENETICHealthy
Healthy Volunteers
GENETICPKD Patients
PKS Patients
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Any Subject: Inclusion Criteria: * Male or female, age: \>18 years. * Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. * Sufficiently fluent in English that they are able to understand written and spoken instructions in the opinion of the investigator.
Exclusion criteria
* Subjects with previous or current drug or alcohol dependence within 2 years of screening. * Subjects who are unable to tolerate study procedures including MRI, or who are unable to perform the study procedures (e.g. due to severe musculoskeletal disease). * Use of other prescription or non-prescription centrally acting drugs, including herbal (eg khat) and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to the procedures of Day 1, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety. * Pregnant females as determined by positive serum or urine hCG test at screening. * Lactating females. * Unwillingness or inability to follow the procedures outlined in the protocol. * Subject is mentally or legally incapacitated. * Subject meets any of the MRI
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Imaging (fMRI) | Day 1 | Action Selection, Tower of London, Shape manipulation, Emotional processing |
| Cognition | Day 1 | Mini Mental State Examination (MMSE), Reward/punishment learning score, Task-set switching, Attentional set-shifting score, Spatial working memory score |
| Olfactory | Day 1 | Sniffin' sticks |
| Motor / Other | Day 1 | Unified Parkinson's Disease Rating Scale (UPDRS), Beck Depression Inventory (BDI), Parkinson's Disease Sleep Scale (PDSS), Nonmotor Symptoms Questionnaire, Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease, Caffeine/Smoking Questionnaire |
Countries
United Kingdom
Outcome results
None listed