Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Molecular and Functional Imaging in SNCA, Parkin and PINK1

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04084509
Recruitment Status : Withdrawn (Change of circumstances for CI/PI.)
First Posted : September 10, 2019
Last Update Posted : April 6, 2020
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

Tracking Information
First Submitted Date August 8, 2019
First Posted Date September 10, 2019
Last Update Posted Date April 6, 2020
Estimated Study Start Date October 1, 2019
Estimated Primary Completion Date September 30, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: September 9, 2019)
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.
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures Not Provided
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Molecular and Functional Imaging in SNCA, Parkin and PINK1
Official Title Molecular and Functional Imaging of Parkinson's Pathology in SNCA, Parkin and PINK1 Mutation Carriers
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.

Detailed Description Not Provided
Study Type Observational
Study Design Observational Model: Case-Control
Time Perspective: Cross-Sectional
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
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)
Condition
  • Parkinson Disease
  • PARK1
  • PARK2
Intervention Not Provided
Study Groups/Cohorts
  • Healthy Controls
  • Idiopathic Parkinson's Disease
  • Symptomatic Genetic Carriers (SNCA, Parkin or PINK1)
  • Asymptomatic Genetic Carriers (SNCA, Parkin or PINK1)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Withdrawn
Actual Enrollment
 (submitted: April 2, 2020)
0
Original Estimated Enrollment
 (submitted: September 9, 2019)
44
Estimated Study Completion Date September 30, 2022
Estimated Primary Completion Date September 30, 2022   (Final data collection date for primary outcome measure)
Eligibility 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.
Sex/Gender
Sexes Eligible for Study: All
Ages 25 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers Yes
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number NCT04084509
Other Study ID Numbers 263369
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: Undecided
Responsible Party King's College London
Study Sponsor King's College London
Collaborators
  • King's College Hospital NHS Trust
  • Michael J. Fox Foundation for Parkinson's Research
Investigators
Principal Investigator: Marios Politis, MD MSc PhD King's College London
PRS Account King's College London
Verification Date August 2019