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Parkinson DiseasePhase 1NCT01424475

LRRK2 Mutation and Parkinson's Disease

A Phase 1 study testing Healthy and PKD Patients in people with Parkinson Disease, run by GlaxoSmithKline at 1 site in United Kingdom.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for
Parkinson Disease
What is being tested?
Healthy and PKD Patients
Could I receive a placebo?
No, everyone receives an active treatment
How many people
5 participants
Where
1 siteUnited Kingdom
Study dates
11 Aug 2011to 12 Jan 2015
Phase
Phase 1
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 18 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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.
  • 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):
  • 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.
  • 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exposure
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  • Parkinson's disease in Hoehn \& Yahr criteria Stages I-III.
  • Confirmed ascertainment as having the G2019S mutation in the LRRK2 gene.
  • Matched to patients with LRRK2 mutation for age, gender, premorbid reading IQ, handedness and smoking status (number of cigarettes smoked per day (0-10, 11-20, 21-30 or 30+)).
  • None of the clinical symptoms or signs of Parkinson's disease listed in section 5.2.2.1.
  • No family history of more than one first-degree relative with Parkinson's disease to suggest that the subject may be a carrier of one of the genetic mutations of Parkinson's disease.
  • Confirmed ascertainment as not having LRRK2 mutation.
  • Subject is not a genetically-related family member of a subject with LRRK2 mutation recruited into this study as per criteria above.
  • Subject is healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
  • No current or past history of Axis I psychiatric disorders as determined by MINI interview.

Who cannot join

  • 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.
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  • Subject is mentally or legally incapacitated.
  • Subject meets any of the MRI exclusion criteria.
  • Subject is left-handed.
  • PKD Patients:
  • 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]).
  • Subjects with prior or current major psychosis (e.g. schizophrenia or psychotic depression) as assessed by the MINI neuropsychiatric interview.
  • Subjects with severe clinical dementia as measured by UPDRS.
  • Patients who are on centrally acting anti-cholinergic medication that is likely to impair cognitive function.
  • Patients with positive drug screen results may still be included at the discretion of the investigator following a discussion of the result with the subject, and following a discussion with the sponsor.
  • Healthy Subjects (Controls):
  • A positive pre-study drug/alcohol screen.
  • Currently taking any prescription medication, in particular medication with a central mechanism of action, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

  • GSK Investigational Site

    Cambridge, CB2 2GG

Other trials in United Kingdom

About this study

Official title: LRRK2 Mutation and Parkinson's Disease: A Functional Neuroimaging and Behavioural Study Characterising the Neurocognitive Phenotype

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.

Read the 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.

Being tested
Healthy, PKD Patients
Medical subject headings
Parkinson Disease

What participants receive

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

  • HealthyGenetic

    Healthy Volunteers

  • PKD PatientsGenetic

    PKS Patients

Study groups in NCT01424475
Study groupRoleWhat they receive
PKD PatientsOtherPKD Patients with LRRK2 mutation
Receives: Genetic: PKD Patients
Healthy ControlsOtherHealthy Controls with no LRRK2 mutation
Receives: Genetic: Healthy

What is being measured

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

  1. Imaging (fMRI)

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

    Measured: Day 1

  2. Cognition

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

    Measured: Day 1

  3. Olfactory

    Sniffin' sticks

    Measured: Day 1

  4. 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

    Measured: Day 1

Timeline

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

  1. First posted29 Aug 2011 (estimated)
  2. Study start11 Aug 2011
  3. Primary completion12 Jan 2015
  4. Study completion12 Jan 2015

Why it stopped: Following extensive efforts to increase recruitment, it will not be possible to complete the study protocol within a reasonable time

Resources

More details

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

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Other
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
5 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01424475
Sponsor's protocol ID
114500
Status last verified
May 2017
First submitted
23 Jun 2011
Last updated
11 May 2017
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Healthy and PKD Patients in people with Parkinson Disease, run by GlaxoSmithKline at 1 site in United Kingdom.

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 15 inclusion and 18 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: stopped early, as of the sponsor's last update on 11 May 2017. 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 Kingdom. 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.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Following extensive efforts to increase recruitment, it will not be possible to complete the study protocol within a reasonable time). Results are not available in the source record.

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?

Imaging (fMRI) (time frame: Day 1). The study lists 4 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 NCT01424475.

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 11 May 2017.

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LRRK2 Mutation and Parkinson's Disease (NCT01424475) | AzTrials