Clinical trial NCT05518617: Molecular and Functional Imaging in Monogenic PD.
Official title: Molecular and Functional Imaging of Parkinson's Pathology in SNCA, Parkin and PINK1 Mutation Carriers
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Parkinson Disease
Nervous System Disorder
Neurodegenerative Diseases
Neurodegenerative Disease, Hereditary
Parkinson's
Lead sponsor: University of Exeter
Sponsor class: OTHER
First posted: 2022-08-26
Enrollment: 45
Sex: ALL
Minimum age (years): 25
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
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.

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.

Detailed description: The purpose of this study is to find a biomarker for Parkinson's disease (PD). A biomarker is an indicator of the presence of a disease, that can be measured, and that is able to give information about the progression, or severity, of it.

PD is a chronic neurological disease that progresses over time and causes a variety of symptoms, such as slowness of movement, stiffness and shaking. The symptoms of PD are caused by the malfunction and death of vital nerve cells in the brain. it is no known what causes PD and there is no biomarker for it.

Generally, PD occurs without a known cause, and is called sporadic PD. In a few cases, however, PD occurs because of a genetic mutation, and it is called genetic PD. Patients with genetic PD share features to sporadic PD patients. It is believed that studying people who carry mutations for genetic PD mutations would provide precious information on what are the causes of PD and help to devise successful treatments.

Participants will attend 4 visits in a 3 month period. These visits include an initial consent and assessment visit where some blood samples will also be taken. the second visit involves a PET scan with the tracer DASB along with an MRI scan. The third visit involves a SPECT scan. the fourth visit is optional and would be for a lumbar puncture visit. Each visit will last around 6 hours.

Eligibility criteria: Inclusion Criteria:

* 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 Criteria:

* 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.

Primary outcomes:
measure: DASB (a marker of Serotonin transporter) used to quantify in vivo pathology of serotonin
timeFrame: 3 weeks
measure: SPECT to measure brain molecular pathology
timeFrame: 3 weeks
measure: Magnetic Resonance Imaging (MRI)
timeFrame: 3 weeks
Secondary outcomes:
Other outcomes:
measure: Movement Disorder Society- Unified Parkinson's Disease Rating Scale (MDS-UPDRS) to determine if there is a correlation with neuropsychological and behavioural evaluation.
timeFrame: 3 weeks
measure: Montreal Cognitive Assessment (MOCA) to determine if there is a correlation with neuropsychological and behavioural evaluation
timeFrame: 3 weeks
measure: Cambridge Neuropsychological Test Automated Battery (CANTAB) to determine if there is a correlation with neuropsychological and behavioural evaluation
timeFrame: 3 Weeks
measure: Symbol Digit Modalities Test (SDMT) to determine if there is a correlation with neuropsychological and behavioural evaluation
timeFrame: 3 Weeks
measure: Beck Depression Inventory-II (BDI-II) to determine if there is a correlation with neuropsychological and behavioural evaluation
timeFrame: 3 Weeks
measure: State-Trait Anxiety Inventory (STAI) to determine if there is a correlation with neuropsychological and behavioural evaluation
timeFrame: 3 Weeks
measure: University of Pennsylvania Smell Identification Test to determine if there is a correlation with neuropsychological and behavioural evaluation
timeFrame: 3 Weeks
measure: Movement Disorder Society- Non-Motor Symptoms scale for Parkinson's Disease MDS-NMSS to determine if there is a correlation with neuropsychological and behavioural evaluation
timeFrame: 3 weeks
measure: Scales for Outcomes in Parkinson's Disease-Autonomic questionnaire - Autonomic Dysfunction (SCOPA-AUT) to determine if there is a correlation with neuropsychological and behavioural evaluation
timeFrame: 3 weeks
Locations:
city: Exeter
country: United Kingdom
facility: University Of Exeter
state: Devon
Study officials:
affiliation: The University of Exeter
name: Marios Politits, Professor
role: PRINCIPAL_INVESTIGATOR
References: