Clinical trial NCT05516719: Longitudinal Investigation of I2BS in PD
Official title: Longitudinal Investigation of Imidazoline-2 Binding Site As a Novel Marker of Disease Progression in Parkinson's Disease: an [11C]BU99008 PET Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Parkinson's
Parkinson Disease
Parkinson's Disease
Neurodegenerative Diseases
Neurodegeneration
Positron Emission Tomography
Lead sponsor: University of Exeter
Sponsor class: OTHER
First posted: 2022-08-26
Enrollment: 44
Sex: ALL
Minimum age (years): 25
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: A cohort of carriers of SNCA genetic mutations for familial forms of Parkinson's Disease, idiopathic Parkinson's Disease patients and previously collected data from healthy controls

Brief summary: 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

Detailed 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.

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.
* 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;

Primary outcomes:
measure: PET scan with BU99008 to highlight I2BS and and Astroglia cells.
timeFrame: 12 Months
measure: Single Photon Emission Computed Tomography (SPECT) to measure brain molecular pathology
timeFrame: 12 Months
measure: Magnetic Resonance Imaging (MRI)
timeFrame: 12 Months
Secondary outcomes:
Other outcomes:
measure: Movement Disorder Society- Unified Parkinson's Disease Rating Scale (MDS-UPDRS)
timeFrame: 12 Months
measure: Montreal Cognitive Assessment (MOCA) to determine if there is a correlation with neuropsychological and behavioural evaluation
timeFrame: 12 Months
measure: Cambridge Neuropsychological Test Automated Battery (CANTAB) to determine if there is a correlation with neuropsychological and behavioural evaluation
timeFrame: 12 Months
measure: Symbol Digit Modalities Test (SDMT) to determine if there is a correlation with neuropsychological and behavioural evaluation
timeFrame: 12 Months
measure: Beck Depression Inventory-II (BDI-II) to determine if there is a correlation with neuropsychological and behavioural evaluation
timeFrame: 12 Months
measure: State-Trait Anxiety Inventory (STAI) to determine if there is a correlation with neuropsychological and behavioural evaluation
timeFrame: 12 Months
measure: University of Pennsylvania Smell Identification Test (UPSIT) to determine if there is a correlation with neuropsychological and behavioural evaluation
timeFrame: 12 Months
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: 12 Months
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: 12 Months
Locations:
city: Exeter
country: United Kingdom
facility: University Of Exeter
state: Devon
Study officials:
affiliation: University of Exeter
name: Marios Politis, Professor
role: PRINCIPAL_INVESTIGATOR
References: