LRRK2 Mutation and Parkinson's Disease

NCT01424475 | Terminated Phase 1

• 1 other identifier: 114500
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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.

Conditions

Parkinson Disease

Outcome Measures

Primary Outcomes (4)

• Imaging (fMRI)

  Action Selection, Tower of London, Shape manipulation, Emotional processing

  Day 1

• Cognition

  Mini Mental State Examination (MMSE), Reward/punishment learning score, Task-set switching, Attentional set-shifting score, Spatial working memory score

  Day 1

• Olfactory

  Sniffin' sticks

  Day 1

• Motor / Other

  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

  Day 1

Study Arms (2)

PKD Patients

OTHER

PKD Patients with LRRK2 mutation

Genetic: PKD Patients

Healthy Controls

OTHER

Healthy Controls with no LRRK2 mutation

Genetic: Healthy

Interventions

Healthy GENETIC

Healthy Volunteers

Healthy Controls

PKD Patients GENETIC

PKS Patients

PKD Patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 is left-handed.
• PKD Patients:
• Diagnosis of Parkinson's disease according to the following criteria derived from the UKPD Society brain bank diagnostic criteria for PD (Hughes AJ et al., 1992):
• a) Bradykinesia must be present b) At least one of the following: muscular rigidity Resting tremor postural instability not caused by primary visual, vestibular, cerebellar or proprioceptive dysfunction c) Supportive prospective positive criteria for Parkinson's Disease (three of the following required for definite diagnosis): Resting tremor unilateral onset progressive disorder in first 5 years following onset, persistent asymmetry affecting side on which symptoms first appeared excellent response (70-100%) to levodopa in the clinical judgement of the investigator, based on the medical notes or during standard care d) None of the following clinical features which suggest a diagnosis other than Parkinson's disease: History of repeated strokes with stepwise symptom progression History of repeated head injury History of definite encephalitis Neuroleptic treatment at symptom onset Sustained remission Strictly unilateral features after 3 years Supranuclear gaze palsy Cerebellar signs In first five years following onset, early severe autonomic involvement such as orthostatic hypotension, impotence and bladder dysfunction Early (within 2 years on symptom onset) severe dementia with disturbed memory, language, praxis Babinski sign CT/MRI scan evidence of tumour or hydrocephalus Negative response to 1000mg of levodopa daily in divided doses.
• methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exposure
• Parkinson's disease in Hoehn \& Yahr criteria Stages I-III.
• Confirmed ascertainment as having the G2019S mutation in the LRRK2 gene.
• Subjects with clinically significant condition(s) other than Parkinson's disease which, in the opinion of the investigator, would render the subject unsuitable for the study (e.g. psychiatric, haematological, renal, hepatic, endocrinology, neurological \[other than Parkinson's disease\], cardiovascular, or active malignancy \[other than benign skin malignancies\]).

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Cambridge, CB2 2GG, United Kingdom

Location

Related Links

• Results for study 114500 can be found on the GSK Clinical Study Register.

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

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2011
• First Posted: August 29, 2011
• Study Start: August 11, 2011
• Primary Completion: January 12, 2015
• Study Completion: January 12, 2015
• Last Updated: May 11, 2017

Record last verified: 2017-05

Locations

GB (1)