RecruitingNCT05518617

Molecular and Functional Imaging in Monogenic PD.

Molecular and Functional Imaging of Parkinson's Pathology in SNCA, Parkin and PINK1 Mutation Carriers

Sponsor

University of Exeter

Enrollment

45 participants

Start Date

Jul 1, 2022

Study Type

OBSERVATIONAL

Conditions

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

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.

Eligibility

Min Age: 25 YearsMax Age: 80 Years

Inclusion Criteria16

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 DaTSCANä imaging.

Exclusion Criteria12

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.
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.

Interventions

OTHERPositron Emission Tomography (PET) scan using DASB tracer

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,