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Molecular and Functional Imaging in SNCA, Parkin and PINK1

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ClinicalTrials.gov Identifier: NCT04084509
Recruitment Status : Not yet recruiting
First Posted : September 10, 2019
Last Update Posted : September 10, 2019
Sponsor:
Collaborators:
King's College Hospital NHS Trust
Michael J. Fox Foundation for Parkinson's Research
Information provided by (Responsible Party):
King's College London

Brief Summary:

Parkinson's Disease (PD) is a progressive neurodegenerative disease characterized clinically by bradykinesia, resting tremor, rigidity, and postural instability. The hallmark pathophysiological alteration is a loss of dopaminergic transmission across the nigrostriatal pathway. According to Braak's neuropathological staging of disease, the pathological process in PD occurs in a gradual ascending fashion, starting from the olfactory bulb and progressing to the brainstem, with preferential involvement of the raphe nuclei, which contain serotonergic nuclei, and the noradrenergic locus coeruleus, before involving the substantia nigra and thereafter the whole brain. 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 causing, the so-called monogenic parkinsonism, have been discovered providing important insights on the pathogenesis of PD.

The objective of the study is to characterize the molecular phenomena underlying genetic forms of parkinsonism and, therefore, providing further insights about the possible mechanisms taking place in PD and help identify targets for disease-modifying therapeutics, by using PET imaging with [11C]DASB (a marker of Serotonin transporter), SPECT imaging using [123I]FP-CIT (a marker of the presynaptic Dopamine transporter), and multi-modal MRI imaging, clinical markers (motor and non-motor symptoms and neuropsychological battery), blood and CSF biomarkers.


Condition or disease
Parkinson Disease PARK1 PARK2

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Study Type : Observational
Estimated Enrollment : 44 participants
Observational Model: Case-Control
Time Perspective: Cross-Sectional
Official Title: Molecular and Functional Imaging of Parkinson's Pathology in SNCA, Parkin and PINK1 Mutation Carriers
Estimated Study Start Date : October 1, 2019
Estimated Primary Completion Date : September 30, 2022
Estimated Study Completion Date : September 30, 2022


Group/Cohort
Healthy Controls
Idiopathic Parkinson's Disease
Symptomatic Genetic Carriers (SNCA, Parkin or PINK1)
Asymptomatic Genetic Carriers (SNCA, Parkin or PINK1)



Primary Outcome Measures :
  1. Primary Outcomes [ Time Frame: Up to 21 days ]
    To quantify serotonergic and dopaminergic pathology in carriers of genetic mutations for familial forms of Parkinsonism, idiopathic PD patients and healthy controls.



Information from the National Library of Medicine

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Ages Eligible for Study:   25 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population
Healthy Controls Idiopathic Parkinson's Disease Symptomatic Genetic Carriers (SNCA, Parkin or PINK1) Asymptomatic Genetic Carriers (SNCA, Parkin or PINK1)
Criteria

Inclusion Criteria (for all subjects):

  • All subjects must be judged by the investigator able to understand the nature, design, and procedures of the study and must be able to provide a signed and dated informed consent in accordance with Good Clinical Practice (GCP), International Conference on Harmonization (ICH), and local regulations.
  • All subjects must be willing and able to comply with scheduled visits, required study procedures and laboratory tests.
  • All subjects must be able to travel to the research sites for the study procedures.
  • For female subjects: They must be either of non-childbearing potential (either surgically sterile or post- menopausal - defined as 12 months of spontaneous amenorrhea), or, if of childbearing potential, subjects must demonstrate to be non-pregnant (as demonstrated by negative urine β-HCG test at screening), non-breastfeeding.
  • All subjects must comply with highly effective contraceptive measures. A highly effective contraceptive measure is defined as a measure that can achieve a failure rate of less than 1% per year when used consistently and correctly. These methods are listed in more detail below:

Oral, intravaginal, or transdermal combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation;

Oral, injectable, or implantable progestogen-only hormonal contraception associated with inhibition of ovulation:

Intrauterine device (IUD) Intrauterine hormone-releasing system (IUS) Bilateral tubal occlusion Vasectomised partner Sexual abstinence

  • For sexually active male subjects, they must agree to use condoms to protect their partners from becoming pregnant for the duration of the study and for 3 months after the last administration of PET or SPECT ligands. They must also agree to ensure that they and their partners are routinely using a medically approved contraceptive method. It is important that male subjects not impregnate others for the duration of the study and for 3 months after the last administration of PET or SPECT ligands.
  • All subjects must have adequate visual and auditory acuity according to investigator's judgement to complete the psychological testing.
  • All subjects must have no use of medications with known interaction with serotonergic transmission (e.g. selective serotonin reuptake inhibitors, tricyclic antidepressant, triptans, etc).
  • For subjects taking any drugs that might interfere with dopamine transporter SPECT imaging (neuroleptics, metoclopramide, alpha methyldopa, methylphenidate, reserpine, or amphetamine derivative) must be willing and able from a medical standpoint to hold the medication for at least 5 half-lives prior to screening DaTSCAN imaging.

Exclusion Criteria (for all subjects):

  • Subjects lacking capacity according to investigator judgement.
  • Subjects with a clinical diagnosis of dementia as determined by the investigator.
  • Current treatment with anticoagulants (e.g. coumadin, heparin) that might preclude safe completion of the lumbar puncture.
  • Condition that precludes the safe performance of routine lumbar puncture, such as prohibitive lumbar spinal disease, bleeding diathesis, or clinically significant coagulopathy or thrombocytopenia.
  • Use of any of the following drugs that might interfere with dopamine transporter SPECT imaging: neuroleptics, metoclopramide, alpha methyldopa, methylphenidate, reserpine, or amphetamine derivative, within 5 months of Screening.
  • Use of investigational drugs or devices within 60 days prior to Baseline (dietary supplements taken outside of a clinical trial are not exclusionary, e.g., coenzyme Q10).
  • History of cancer within the last 5 years, with the exception of non-metastatic basal cell carcinoma of the skin.
  • Subjects with current or recent history of drug or alcohol abuse/dependence.
  • Contraindication to MRI, such as presence of metal devises or implants (e.g. pacemaker, vascular- or heart- valves, stents, clips), metal deposited in the body (e.g. bullets or shells), or metal grains in the eyes;
  • Claustrophobia or history of back pain that makes prolonged laying on the PET or MRI scanner intolerable.
  • Previously obtained MRI scan with evidence of clinically significant neurological disorder (in the opinion of the Investigator).
  • Any other medical or psychiatric condition or lab abnormality, which in the opinion of the investigator might preclude participation.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04084509


Contacts
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Contact: Marios Politis, MD MSc PhD 02078485682 marios.politis@kcl.ac.uk
Contact: Chloe Farrell, PhD 02078485452 chloe.farrell@kcl.ac.uk

Sponsors and Collaborators
King's College London
King's College Hospital NHS Trust
Michael J. Fox Foundation for Parkinson's Research
Investigators
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Principal Investigator: Marios Politis, MD MSc PhD King's College London

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Responsible Party: King's College London
ClinicalTrials.gov Identifier: NCT04084509     History of Changes
Other Study ID Numbers: 263369
First Posted: September 10, 2019    Key Record Dates
Last Update Posted: September 10, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases