Molecular and Functional Imaging in Monogenic PD.

NCT05518617 | Recruiting

• 1 other identifier: 2020-21-14
• Study Type: observational
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

In this study, the investigators aim to find a biomarker of Parkinson's disease. This is done using imaging scans called Positron Emission tomography (PET), Single Photon Emission Computed Tomography (SPECT), and Magnetic Resonance Imaging (MRI). The findings will provide a deeper understanding of the brain changes in Parkinson's disease. More importantly, this study will help with the discovery and development of new medications aiming to delay progression of PD symptoms.

Conditions

Parkinson Disease; Nervous System Disorder; Neurodegenerative Diseases; Neurodegenerative Disease, Hereditary; Parkinson's

Outcome Measures

Primary Outcomes (3)

• DASB (a marker of Serotonin transporter) used to quantify in vivo pathology of serotonin

  To quantify serotonergic pathology with \[11C\]3-amino-4-(2- imethylaminomethylphenylsulfanyl)-benzonitrile (DASB) Positron Emission Tomography (PET)

  3 weeks

• SPECT to measure brain molecular pathology

  To quantify serotonergic pathology with \[11C\]DASB PET and dopaminergic pathology with Single-photon Emission Computed Tomography (SPECT)

  3 weeks

• Magnetic Resonance Imaging (MRI)

  Magnetic Resonance Imaging (MRI) to view structural and microstructural changes and structural connectivity.

  3 weeks

Other Outcomes (9)

• Movement Disorder Society- Unified Parkinson's Disease Rating Scale (MDS-UPDRS) to determine if there is a correlation with neuropsychological and behavioural evaluation.

  3 weeks

• Montreal Cognitive Assessment (MOCA) to determine if there is a correlation with neuropsychological and behavioural evaluation

  3 weeks

• Cambridge Neuropsychological Test Automated Battery (CANTAB) to determine if there is a correlation with neuropsychological and behavioural evaluation

  3 Weeks

Study Arms (4)

SNCA (Alpha-synuclein gene)

PET and SPECT molecular imaging and MRI; Clinical investigation and computerized neuropsychological testing; Collection of blood, urine and CSF biomarkers of PD pathology.

Other: Positron Emission Tomography (PET) scan using DASB tracer

Parkin (Parkin gene)

PET and SPECT molecular imaging and MRI; Clinical investigation and computerized neuropsychological testing; Collection of blood, urine and CSF biomarkers of PD pathology

Other: Positron Emission Tomography (PET) scan using DASB tracer

PINK1 (Phosphatase and Tensin Homolog (PTEN)-Induced Kinase 1 gene)

PET and SPECT molecular imaging and MRI; Clinical investigation and computerized neuropsychological testing; Collection of blood, urine and CSF biomarkers of PD pathology

Other: Positron Emission Tomography (PET) scan using DASB tracer

GBA1 (Glucosylceramidase beta gene)

Symptomatic and asymptomatic heterozygous carriers of risk variants to the GBA1 gene for Parkinson's disease

Interventions

Positron Emission Tomography (PET) scan using DASB tracer OTHER

DASB is a highly selective PET radioligand for serotonin transporter and is a reliable tool to investigate serotonin terminals and neurons. The included Magnetic Resonance Imaging (MRI) sequences serve to provide additional information plus complement PET data. To quantify dopaminergic pathology with \[123I\]FP-CIT SPECT,

Also known as: FP-CIT Single-photon Emission Computed Tomography (SPECT) scan, Magnetic Resonance Imaging (MRI) Scan, Lumbar puncture

PINK1 (Phosphatase and Tensin Homolog (PTEN)-Induced Kinase 1 gene); Parkin (Parkin gene); SNCA (Alpha-synuclein gene)

Eligibility Criteria

• Age: 25 Years - 80 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

A cohort of asymptomatic and symptomatic carriers of genetic mutations for familial forms of Parkinson's Disease, and previously collected data from healthy controls.

You may qualify if:

• 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).

You may not qualify if:

• 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. warfarin, 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.
• 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.

Sponsors & Collaborators

• University of Exeter: lead

Study Sites (1)

University Of Exeter

Exeter, Devon, EX1 2LU, United Kingdom

RECRUITING

Related Links

• University of Exeter, Project infromation

Biospecimen

Retention: SAMPLES WITH DNA

Biosamples collected during this study will be blood, urine, and CSF. Blood biomarkers include routine clinical laboratory, DNA testing, and other analyses.

MeSH Terms

Conditions

Parkinson Disease; Nervous System Diseases; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System

Interventions

Magnetic Resonance Spectroscopy; 2-phenyl-6-(2'-(4'-(ethoxycarbonyl)thiazolyl))thiazolo(3,2-b)(1,2,4)triazole; Spinal Puncture

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Movement Disorders; Synucleinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques; Biopsy; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Neurological; Punctures; Therapeutics; Surgical Procedures, Operative

Study Officials

• Marios Politits, Professor

  The University of Exeter

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marios Politis, Professor

CONTACT

07503 741242; m.politis@exeter.ac.uk

Edoardo de Natale, Dr

CONTACT

07503 741242; e.de-natale@exeter.ac.uk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2022
• First Posted: August 26, 2022
• Study Start: July 1, 2022
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: October 7, 2025

Record last verified: 2025-10

Locations

GB (1)