Longitudinal Investigation of I2BS in PD (FOX_2)

University of Exeter

Status: Enrolling

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

Treatments: Other: Positron Emission Tomography (PET) scan using BU99008 tracer; Other: Lumbar puncture; Other: Magnetic Resonance Imaging (MRI) Scan; Other: FP-CIT Single-photon Emission Computed Tomography (SPECT) scan

Study type: Observational

Funder types: Other

Identifiers

NCT05516719

2020-21-15

Details and patient eligibility

About

In this study, the researchers aim to find a biomarker of PD. Using imaging scans called Positron Emission tomography (PET), Single Photon Emission Computed Tomography (SPECT), and Magnetic Resonance Imaging (MRI). The PET and SPECT scans use small amounts of radiation and specific compounds called tracers, to study chemical changes in the brain in a way not possible with any other procedure. The MRI uses magnetic fields to generate images of brain structure and function

Full description

Parkinson's disease is a chronic neurological disease that progresses over time and causes a variety of symptoms, such as slowness of movement, stiffness and shaking. The purpose of this study is to find a biomarker for Parkinson's disease. A biomarker is an indicator of the presence of a disease, that can be measured, and that is able to give information.

The study will take place in London, in three research sites that are located near to each other. The NIHR Imperial Clinical Research Facility (CRF) at Hammersmith Hospital in London, for clinical assessment, and Invicro London for imaging assessments. Both Hammersmith Hospital and Invicro are located at Hammersmith Hospital Campus.

Taking part in this study will involve two sets of visits spaced out 12 months apart. These visits would include, initial screening and consent visit. The second visit would be for an MRI and PET scan with the tracer BU99008 which highlights astroglia cells. The third visit would be for a SPECT scan, and an optional fourth visit for a Lumbar Puncture procedure to collect spinal fluid for analysis.

These visits are then repeated 12 months later to form a comparison. The maximum number of visits for this study would be 8, however two of these visits are optional lumbar puncture visits.

The findings form this research 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. n about the progression, or severity, of it.

Enrollment: 44 estimated patients

Sex: All

Ages: 25+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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.
• Age 25 years or older.
• 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 I2BS (e.g. idaxozan, efaroxan, yohimbine, atomoxetine, atipamezole, mianserin, mirtazapine, clonidine, guanfacine, guanabenz, guanethidine, xylazine, tizanidine, tedetomidine, methyldopa, fadolmidine, dexmedetomidine)
• 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's judgment;
• Subjects with a clinical diagnosis of dementia as determined by the investigator;
• Subjects with current or a recent history of drug or alcohol abuse/dependence;
• Current treatment with anticoagulants (e.g. warfarin, heparin) that might preclude the arterial cannulation and the 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.
• Negative Allen test in both hands,
• 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 any medications with known actions on I2BS (e.g. idaxozan, efaroxan, yohimbine, atomoxetine, atipamezole, mianserin, mirtazapine, clonidine, guanfacine, guanabenz, guanethidine, xylazine, tizanidine, tedetomidine, methyldopa, fadolmidine, dexmedetomidine);
• 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, SPECT, or MRI scanner intolerable.
• Previously obtained MRI scan with evidence of clinically significant neurological disorder (in the opinion of the Investigator).
• 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 behavior or active suicidal ideation;
• Pregnancy or breastfeeding or intent to become pregnant in the next 18 months;

Trial design

44 participants in 3 patient groups

SNCA (Alpha-synuclein gene)

Description:

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

Treatment:

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

Other: Magnetic Resonance Imaging (MRI) Scan

Other: Lumbar puncture

Other: Positron Emission Tomography (PET) scan using BU99008 tracer

Idiopathic Parkinson's Disease

Description:

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

Treatment:

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

Other: Magnetic Resonance Imaging (MRI) Scan

Other: Lumbar puncture

Other: Positron Emission Tomography (PET) scan using BU99008 tracer

Healthy Control

Description:

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

Treatment:

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

Other: Magnetic Resonance Imaging (MRI) Scan

Other: Lumbar puncture

Other: Positron Emission Tomography (PET) scan using BU99008 tracer