Serotonin Release in Premotor and Motor PD

NCT05516732 | Recruiting

• 1 other identifier: 2020-21-16
• Study Type: observational
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

In this study, the investigators aim to provide a deeper understanding of Parkinson's disease and 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 Parkinson's disease symptoms

Conditions

Parkinson Disease; Parkinson's; Parkinson's Disease; Neurodegenerative Diseases; Neurodegeneration; Positron Emission Tomography

Outcome Measures

Primary Outcomes (4)

• 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

• CIMBI to measure serotonin release

  CIMBI-36 can be interpreted to show serotonin release capacity both quantifiably and locational.

  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 (2)

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 CIMBI-36 tracer; Other: Magnetic Resonance Imaging (MRI) Scan; Other: Positron Emission Tomography (PET) scan using DASB tracer; Other: FP-CIT Single-photon Emission Computed Tomography (SPECT) scan; Other: Lumbar puncture

Idiopathic Parkinson's Disease

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 CIMBI-36 tracer; Other: Magnetic Resonance Imaging (MRI) Scan; Other: Positron Emission Tomography (PET) scan using DASB tracer; Other: FP-CIT Single-photon Emission Computed Tomography (SPECT) scan; Other: Lumbar puncture

Interventions

Positron Emission Tomography (PET) scan using CIMBI-36 tracer OTHER

This scan creates images of regional serotonin release in by using a tracer compound called CIMBI to highlight the brains capacity to release serotonin.

Idiopathic Parkinson's Disease; SNCA (Alpha-synuclein gene)

Magnetic Resonance Imaging (MRI) Scan OTHER

MRI (magnetic resonance imaging) uses magnets alongside radio waves to create pictures of the brain

Idiopathic Parkinson's Disease; SNCA (Alpha-synuclein gene)

Positron Emission Tomography (PET) scan using DASB tracer OTHER

To create images of the brain using a tracer called DASB, which is a highly selective for serotonin transporters, this highlights serotonin terminals and neurons in the brain.

Idiopathic Parkinson's Disease; SNCA (Alpha-synuclein gene)

FP-CIT Single-photon Emission Computed Tomography (SPECT) scan OTHER

A single-photon emission computerized tomography (SPECT) scan allows analysis of brain function by creating 3D Pictures using compounds called tracers.

Idiopathic Parkinson's Disease; SNCA (Alpha-synuclein gene)

Lumbar puncture OTHER

A lumbar puncture invovles a thin needle is inserted between the bones in your lower spine using local anaesthetic. This allows the collection of Cerebrospinal fluid ( CSF)

Idiopathic Parkinson's Disease; SNCA (Alpha-synuclein gene)

Eligibility Criteria

• Age: 25 Years - 85 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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

You may qualify if:

• Subjects must understand the nature of the study and must provide signed and dated written HRA-approved informed consent in accordance with local regulations before any protocol-specific screening procedures are performed;
• Males and females, age 25-85 years, inclusive;
• Women of child-bearing potential must use protocol-defined contraceptive measures and must have a negative β-hCG test at screening. For sexually active subjects (except females of non-childbearing potential-e.g., at least 2 years postmenopausal or surgically sterile), condoms should be used in addition to other birth control methods for the duration of the study and for 3 months after the last administration of PET or SPECT ligands. These patients must be willing to remain on their current form of contraception for the duration of the study. All male subjects must agree to refrain from donating sperm for the duration of the study and for 3 months after the last administration of PET or SPECT ligands. Sexually active male subjects 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 (i.e. for 15 consecutive months following baseline PET and SPECT scans); 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;
• Able and willing to participate in all scheduled evaluations, abide by all study restrictions, and complete all required tests and procedures;
• Adequate visual and auditory acuity to complete the psychological testing;
• In the opinion of the investigator, the subject must be considered likely to comply with the study protocol and to have a high probability of completing the study.

You may not qualify if:

• Subjects lacking capacity according to investigator judgement;
• Subjects taking serotonin acting drugs such as antidepressants (i.e. tricyclic or selective serotonin reuptake inhibitors etc.);
• Pregnancy or breastfeeding or intent to become pregnant in the next 18 months;
• Subjects with current or a recent history of drug or alcohol abuse/dependence;
• Subjects who have other neurological disorders and known intracranial co-morbidities such as stroke, hemorrhage, space-occupying lesions;
• Presence of any clinically significant medical condition (including cardiovascular, respiratory, cerebrovascular, hematological, hepatic, renal, gastrointestinal, or other disease) that, based on the judgment of the investigator, is clinically unstable, is likely to deteriorate during the course of the study, could put the patient at risk because of participation in the study, could affect the subject's ability to complete the study, or could influence the study results;
• History of suicidal behaviour or active suicidal ideation;
• Within 1 year prior to screen or between screen and baseline (Day -1), any of the following: myocardial infarction; hospitalization for congestive heart failure; hospitalization for, or symptoms of, unstable angina; or syncope not related to PD;
• History or presence of renal disease or impaired renal function;
• Clinically important infection (e.g., chronic, persistent, or acute infection) within 30 days prior to screen or between screen and baseline (Day -1);
• History of cancer within the last 5 years, with the exception of nonmetastatic basal cell carcinoma of the skin;
• Clinically significant blood clotting or bleeding disorder, including clinically significant abnormal findings in laboratory assessments of coagulation or hematology;
• Use of antipsychotic medication within 3 months prior to screen or between screen and baseline (Day -1);
• Use of any anticoagulant within 30 days prior to baseline and follow-up PET scans;
• Use of any oral corticosteroid within 30 days prior to baseline and follow-up PET scans;

Sponsors & Collaborators

• University of Exeter: lead

Study Sites (1)

University Of Exeter

Exeter, Devon, EX1 2LU, United Kingdom

RECRUITING

Related Links

• University of Exeter brief project information webpage

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; Neurodegenerative Diseases; Nerve Degeneration

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; Nervous System Diseases; Movement Disorders; Synucleinopathies; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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 M Politis, Professor

  University of Exeter

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marios Politis, Professor

CONTACT

07503741242; M.Politis@exeter.ac.uk

Edoardo De Natale, Dr

CONTACT

07503741242; 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: August 24, 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)