Parkinson Disease, PARK8NCT03782753
Molecular Pathology and Neuronal Networks in LRRK2 Parkinson's Disease
An observational study of Parkinson Disease, PARK8 and Parkinson Disease, run by King's College London at 1 site in United Kingdom.
Trial summary
Parkinson's Disease (PD) is a progressive neurodegenerative disease characterized clinically by bradykinesia, resting tremor, rigidity, and postural instability. Little is known about the mechanisms underlying neuronal degeneration in PD and currently, no treatment is available to halt disease progression in PD. Read more about this study
- Who is it for?
- Ages 30 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Parkinson Disease, PARK8, Parkinson Disease, Idiopathic Parkinson Disease
- How many people
- 59 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 15 Feb 2019to 23 Jun 2023
- 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 30 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: LRRK2 PD patients, idiopathic PD patients and healthy controls.
Who may be able to join
- All groups
- Women of child-bearing potential must use protocol-defined contraceptive measures and must have a negative β-hCG test at screening. For sexually active subjects (except females of non-childbearing potential), condoms should be used in addition to other birth control methods during the study, for 15 days after the last dose of investigational drug, and for 3 months after the last administration of PET or SPECT ligands. All male subjects must agree to refrain from donating sperm during the study, for 15 days following the last dose of investigational drug, and for 3 months after the last administration of PET or SPECT ligands. It is important that male subjects not impregnate others while in the study.
- Adequate visual and auditory acuity to complete the psychological testing.
- Idiopathic PD group
- Clinical diagnosis of Parkinson's disease meeting the Movement Disorder Society Clinical Diagnostic Criteria (i.e. not induced by drugs or other diseases or carriers of PD risk genes such as LRRK2, SNCA, PARK2 etc.).
- Hoehn and Yahr scale stage 1 or 2.
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- Patients who are drug-naïve (never been treated with dopamine agonists or levodopa) or on dopamine replacement therapy.
- Patients who have received the diagnosis of idiopathic PD within three years for drug-naïve patients or within eight years for patients on dopamine replacement therapy.
- LRRK2 PD group
- Clinical diagnosis of Parkinson's disease meeting the Movement Disorder Society Clinical Diagnostic Criteria and genetic confirmation of being carriers of LRRK2 PD risk genes, diagnosed after the age of 30 years.
- Hoehn and Yahr scale stage 1 or 2.
- Patients who are drug-naïve (never been treated with dopamine agonists or levodopa) or on dopamine replacement therapy.
- Patients who have received the diagnosis of idiopathic PD within three years for drug-naïve patients or within eight years for patients on dopamine replacement therapy.
Who cannot join
- Patients who had previous surgery for PD (including but not limited to deep brain stimulation [DBS] or cell transplantation).
- Patients who are treated with duodopa or apomorphine.
- Patients taking serotonin acting drugs such as antidepressants (i.e. tricyclic or selective serotonin reuptake inhibitors etc.)
- Patients taking drugs acting on SV2A such as antiepileptics (i.e. levetiracetam or brivaracetam etc.)
- Pregnancy or breastfeeding.
- Patients with current or a recent history of drug or alcohol abuse/dependence.
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- Patients who have other neurological disorders and known intracranial co-morbidities such as stroke, haemorrhage, space-occupying lesions.
- Presence of any clinically significant medical condition (including cardiovascular, respiratory, cerebrovascular, hematological, hepatic, renal, gastrointestinal, or other disease) that, based on the judgment of the investigator, is clinically unstable, is likely to deteriorate during the course of the study, could put the patient at risk because of participation in the study, could affect the subject's ability to complete the study, or could influence the study results.
- History of suicidal behavior or active suicidal ideation.
- Within 1 year prior to screen or between screen and baseline (Day -1), any of the following: myocardial infarction; hospitalization for congestive heart failure; hospitalization for, or symptoms of, unstable angina; or syncope not related to PD.
- History or presence of renal disease or impaired renal function.
- Clinically important infection (e.g., chronic, persistent, or acute infection) within 30 days prior to screen or between screen and baseline (Day -1).
- History of cancer within the last 5 years, with the exception of nonmetastatic basal cell carcinoma of the skin.
- Clinically significant blood clotting or bleeding disorder, including clinically significant abnormal findings in laboratory assessments of coagulation or hematology.
- Use of antipsychotic medication within 3 months prior to screen or between screen and baseline (Day -1).
- Use of any anticoagulant within 30 days prior to baseline PET scan.
- Use of any oral corticosteroid within 30 days prior to baseline PET scan.
- Use of metoclopramide within 30 days prior to baseline (Day -1).
- Use of any thyroid medication within 30 days prior to baseline (Day -1).
- Regular use (e.g., taken > 3 days/week) of narcotic pain medications within 30 days prior to baseline (Day -1).
- Presence of any of the following MRI contraindications: pacemaker; cardiac defibrillator; spinal cord or vagus nerve stimulator; aneurysm clip; artificial heart valve; recent coronary or carotid stent; ear implant; CSF shunt; other implanted medical device (e.g., Swan-Ganz catheter, insulin pump); or metal fragments or foreign objects in the eyes, skin, or body.
- Negative Allen test in both hands, unless the brachial artery is used for arterial cannulation.
- Claustrophobia and history of back pain that makes prolonged laying on the PET or MRI scanner intolerable.
- Initiation or change in pharmacologic therapy for symptoms of PD within 30 days prior to screen or between screen and baseline (Day -1).
- In addition, the following are exclusionary for subjects participating in CSF sampling:
- Any spinal malformations or other aspects (e.g., tattoos) or other clinical findings (e.g., papilledema seen with ophthalmoscopy) that may complicate or contraindicate lumbar puncture, as judged by the investigator.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Longitudinal Study of Molecular Pathology and Neuronal Networks in Leucine-rich Repeat Kinase 2 Carriers and Idiopathic Parkinson's Disease Patients and Healthy Controls Using PET, MR Imaging, and Other Markers of in Vivo Pathology
Parkinson's Disease (PD) is a progressive neurodegenerative disease characterized clinically by bradykinesia, resting tremor, rigidity, and postural instability. Little is known about the mechanisms underlying neuronal degeneration in PD and currently, no treatment is available to halt disease progression in PD.
The pathophysiological characterisation of phenomena occurring in the time window between the pathological start of the disease and the onset of motor symptoms is crucial to develop potential neuroprotective agents.
Read more
Several genes have been discovered providing important insights on the pathogenesis of PD. Mutations of Leucine-rich repeat kinase 2 (LRRK2) are associated with 2-5% of all PD cases in North American Caucasians. LRRK2 is an enzyme that in humans is encoded by the autosomal dominant Parkinson's disease-8 (PARK8) gene, which is associated with an increased risk of PD.
Clinical and digital biomarkers, blood and cerebrospinal fluid (CSF) biomarkers and molecular positron emission tomography (PET) imaging, with specific radioligands, provide invaluable insights to help understand and characterise disease pathophysiology.
The investigators aim to characterize molecular phenomena underlying LRRK2 PD with the hope of providing further insights into possible mechanisms taking place in PD and to help identify targets for disease-modifying therapeutics.
- Keywords
- Parkinson Disease, LRRK2
- Medical subject headings
- Parkinson Disease, Parkinson Disease 8
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 |
|---|---|---|
| Group A | 25 LRRK2-PD patients | |
| Group B | 25 idiopathic PD patients | |
| Group C | 25 HC subjects |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in serotonergic transmission in the ventral and dorsal raphe nuclei, and in raphe projection areas, in LRRK2-PD compared to idiopathic PD.
The study's main outcome measure is changes in serotonergic neurotransmission within specific brain regions. This will be assessed with positron emission tomography (PET) imaging using the readioligand 11C-labeled 3-amino-4 -(2-dimethylaminomethyl-phenylsulfanyl)benzonitrile ([11C]DASB).
Measured: One year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2018
- Study start15 Feb 2019
- Primary completion14 Jan 2021
- Study completion23 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Parkinson Disease, PARK8Studies of the same condition, open and under way.
- More trials run by King's College LondonThe sponsor's other registered studies.
- 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
- Case-control
- Time perspective
- Other
- Enrolment
- 59 participants (actual)
Sponsor and investigators
- Lead sponsor
- King's College London
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03782753
- Sponsor's protocol ID
- 249061
- Status last verified
- Jun 2023
- First submitted
- 14 Dec 2018
- Last updated
- 27 Jun 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Longitudinal Study of Molecular Pathology and Neuronal Networks in Leucine-rich Repeat Kinase 2 Carriers and Idiopathic Parkinson's Disease Patients and Healthy Controls Using PET, MR Imaging, and Other Markers of in Vivo Pathology
- ClinicalTrials.gov ID
- NCT03782753
- Acronym / sponsor ID
- 249061
- Keywords
- Parkinson Disease, LRRK2
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 59 participants (actual)
- Lead sponsor
- King's College LondonUniversity, hospital or other
- Collaborators
- GlaxoSmithKline
- Study start
- 15 Feb 2019 (actual)
- Primary completion
- 14 Jan 2021 (actual)
- Study completion
- 23 Jun 2023 (actual)
- First posted
- 20 Dec 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Parkinson's Disease (PD) is a progressive neurodegenerative disease characterized clinically by bradykinesia, resting tremor, rigidity, and postural instability. Little is known about the mechanisms underlying neuronal degeneration in PD and currently, no treatment is available to halt disease progression in PD.
The pathophysiological characterisation of phenomena occurring in the time window between the pathological start of the disease and the onset of motor symptoms is crucial to develop potential neuroprotective agents.
Several genes have been discovered providing important insights on the pathogenesis of PD. Mutations of Leucine-rich repeat kinase 2 (LRRK2) are associated with 2-5% of all PD cases in North American Caucasians. LRRK2 is an enzyme that in humans is encoded by the autosomal dominant Parkinson's disease-8 (PARK8) gene, which is associated with an increased risk of PD.
Clinical and digital biomarkers, blood and cerebrospinal fluid (CSF) biomarkers and molecular positron emission tomography (PET) imaging, with specific radioligands, provide invaluable insights to help understand and characterise disease pathophysiology.
The investigators aim to characterize molecular phenomena underlying LRRK2 PD with the hope of providing further insights into possible mechanisms taking place in PD and to help identify targets for disease-modifying therapeutics.
Study design
- Observational model
- Case-control
- Time perspective
- Other
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group A | – | –25 LRRK2-PD patients |
| Group B | – | –25 idiopathic PD patients |
| Group C | – | –25 HC subjects |
Who may qualify
- Ages
- 30 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- LRRK2 PD patients, idiopathic PD patients and healthy controls.
Key inclusion criteria (13 listed)
- All groups
- Women of child-bearing potential must use protocol-defined contraceptive measures and must have a negative β-hCG test at screening. For sexually active subjects (except females of non-childbearing potential), condoms should be used in addition to other birth control methods during the study, for 15 days after the last dose of investigational drug, and for 3 months after the last administration of PET or SPECT ligands. All male subjects must agree to refrain from donating sperm during the study, for 15 days following the last dose of investigational drug, and for 3 months after the last administration of PET or SPECT ligands. It is important that male subjects not impregnate others while in the study.
- Adequate visual and auditory acuity to complete the psychological testing.
- Idiopathic PD group
- Clinical diagnosis of Parkinson's disease meeting the Movement Disorder Society Clinical Diagnostic Criteria (i.e. not induced by drugs or other diseases or carriers of PD risk genes such as LRRK2, SNCA, PARK2 etc.).
Key exclusion criteria (26 listed)
- Patients who had previous surgery for PD (including but not limited to deep brain stimulation [DBS] or cell transplantation).
- Patients who are treated with duodopa or apomorphine.
- Patients taking serotonin acting drugs such as antidepressants (i.e. tricyclic or selective serotonin reuptake inhibitors etc.)
- Patients taking drugs acting on SV2A such as antiepileptics (i.e. levetiracetam or brivaracetam etc.)
- Pregnancy or breastfeeding.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Changes in serotonergic transmission in the ventral and dorsal raphe nuclei, and in raphe projection areas, in LRRK2-PD compared to idiopathic PD.
Time frame: One year
The study's main outcome measure is changes in serotonergic neurotransmission within specific brain regions. This will be assessed with positron emission tomography (PET) imaging using the readioligand 11C-labeled 3-amino-4 -(2-dimethylaminomethyl-phenylsulfanyl)benzonitrile ([11C]DASB).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jun 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Parkinson Disease, PARK8 and Parkinson Disease, run by King's College London 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 13 inclusion and 26 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 27 Jun 2023. 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.
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?
Changes in serotonergic transmission in the ventral and dorsal raphe nuclei, and in raphe projection areas, in LRRK2-PD compared to idiopathic PD. (time frame: One year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Jun 2023.