Molecular and Functional Imaging in Monogenic PD.

Parkinson Disease Clinical Trial

— FOX_1  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05518617
• Other study ID #: 2020-21-14
• Status: Recruiting
• Start date: July 1, 2022
• Est. completion date: June 30, 2024

Study information

• Verified date: November 2023
• Source: University of Exeter
• Contact: Marios Politis, Professor
• Phone: 07503 741242
• Email: m.politis[@]exeter.ac.uk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 45
• Est. completion date: June 30, 2024
• Est. primary completion date: June 30, 2024
• Gender: All
• Age group: 25 Years to 80 Years

Eligibility

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 ß-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.

Related Conditions & MeSH terms

• Genetic Diseases, Inborn
• Heredodegenerative Disorders, Nervous System
• Nervous System Diseases
• Nervous System Disorder
• Neurodegenerative Disease, Hereditary
• Neurodegenerative Diseases
• Parkinson Disease
• Parkinson's

Intervention

Other:
• Positron 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,

Locations

Country	Name	City	State
United Kingdom	University Of Exeter	Exeter	Devon

Sponsors (1)

Lead Sponsor	Collaborator
University of Exeter

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Movement Disorder Society- Unified Parkinson's Disease Rating Scale (MDS-UPDRS) to determine if there is a correlation with neuropsychological and behavioural evaluation.	A rating tool used to gauge the course of Parkinson's disease in patients	3 weeks
Other	Montreal Cognitive Assessment (MOCA) to determine if there is a correlation with neuropsychological and behavioural evaluation	A cognitive screening test designed to assist in the detection of mild cognitive impairment. Scored out of 30.	3 weeks
Other	Cambridge Neuropsychological Test Automated Battery (CANTAB) to determine if there is a correlation with neuropsychological and behavioural evaluation	Administered to detect cognitive issues & brain disorders efficiently.	3 Weeks
Other	Symbol Digit Modalities Test (SDMT) to determine if there is a correlation with neuropsychological and behavioural evaluation	To be used in screening for organic cerebral dysfunction sored out of 110	3 Weeks
Other	Beck Depression Inventory-II (BDI-II) to determine if there is a correlation with neuropsychological and behavioural evaluation	A brief, self-report inventory designed to measure the severity of depression symptomatology	3 Weeks
Other	State-Trait Anxiety Inventory (STAI) to determine if there is a correlation with neuropsychological and behavioural evaluation	A commonly used measure of trait and state anxiety. Used to diagnose anxiety and to distinguish it from depressive syndromes	3 Weeks
Other	University of Pennsylvania Smell Identification Test to determine if there is a correlation with neuropsychological and behavioural evaluation	This is used to test the function of an individual's olfactory system	3 Weeks
Other	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	This is a 30-item rater-based scale to assess a wide range of non-motor symptoms in patients with Parkinson's disease	3 weeks
Other	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	A 25 item assessment to evaluate autonomic symptoms in patients with Parkinson's disease	3 weeks
Primary	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
Primary	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
Primary	Magnetic Resonance Imaging (MRI)	Magnetic Resonance Imaging (MRI) to view structural and microstructural changes and structural connectivity.	3 weeks

External Links

•   Parkinson's UK, project infromation
•   University of Exeter, Project infromation