Postitron emission tomography imaging of neuroinflammation in Parkinson´s disease

• Register: EUCTR
• Last refreshed on: 30 April 2018
• Main ID: EUCTR2018-000405-23-FI
• Date of registration: 21/02/2018
• Prospective Registration: Yes
• Primary sponsor: Juha Rinne / PET Centre
• Public title: Postitron emission tomography imaging of neuroinflammation in Parkinson´s disease
• Scientific title: In vivo PET imaging of neuroinflammation in Parkinson’s disease using the purinergic P2X7 receptor ligand [11C]SMW139 (PRI-PD) - PRI-PD
• Date of first enrolment: 27/03/2018
• Target sample size: 14
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-000405-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Finland

Key inclusion & exclusion criteria

Inclusion criteria:
HEALTHY VOLUNTEERS
1. Subject is between 45 and 80 years (male/female).
2. Subject is judged to be in good health by the investigator on the basis of medical history, physical examination including vital signs.
3. Subject’s body mass index is >18 and <30 kg/m2 with max weight of 100 kg
4. Women should be of non-childbearing potential (contraception, postmenopausal, surgically sterile).
5. No clinical evidence of a movement disorder as evidenced by careful neurological examination by a neurologist or a MD instructed by a movement disorder specialist.
PARKINSON´S DISEASE PATIENTS:
1. Subject is between 45 and 80 years (male/female).
2. Subject has a clinical diagnosis of Idiopathic Parkinson’s Disease (IPD) according to UK PD brain bank criteria, with at least 2 of the cardinal signs of the disease: resting tremor, bradykinesia or rigidity.
3. Subject has a modified Hoehn and Yahr stage = 3.
4. Female patients should be of non-childbearing potential (contraception, postmenopausal, surgically sterile).

6. No evidence of cognitive impairment.
7. Unremarkable MRI scan as assessed by expert radiologist, nuclear medicine physician or neurologist. In subjects < 60 years of age, no clinically significant abnormalities are allowed, in subjects >= 60 years of age white matter hyperintensities corresponding to a WML (white matter lesion) score <= 2 (of 3) on the ARWMC scale are acceptable.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 4
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion criteria:
HEALTHY VOLUNTEERS
1. Subject has a history of any major disease that may interfere with the investigations (especially liver and kidney disease, or uncontrolled diabetes).
2. Subject has any history of a major neurological disorder.
3. Subject has elevated likelihood for hereditary Parkinson’s disease as assessed by family history.
4. Subject has a history or evidence of psychiatric disease, especially depression. A Beck Depression Inventory score should be <= 9.
5. Subject has had surgery, significant blood loss (> 500 ml), donated blood or participated in another clinical trial using investigational drug(s) within 30 days prior to the imaging day.
6. Subject is currently a user (including ‘’recreational use’’) of any illicit drugs, including cannabis, or has a history of drug or alcohol abuse.
7. Subject chronically uses anti-inflammatory medication (steroids, non-steroidal anti-inflammatory drugs (NSAID), aspirine, paracetamol, etc.), or other medication known to interact with P2X7 receptors.
8. Uncontrolled hypertension juged by the investigator. .
9. Previous repetitive use of psychotropic medication.
10. Pregnancy or lactation (only for women).
11. Administration of any investigational product within 3 months before the start of the present study.
12. Known or suspected drug, alcohol or other abuse, or positive urine drug screen which may interfere with the study objective as judged by the investigator.
13. History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity as judged by the investigator.
14. Subject has a contra-indication for MRI scanning.
15. Subject suffers from claustrophobia or cannot tolerate confinement during PET or MR scanning procedures; subject cannot lie still for 90 minutes inside the PET system.
16. Subject does not understand the study procedure.
17. Subject is unwilling or unable to perform all of the study procedures, or is considered unsuitable in any way by the principal investigator.
18. Subject has a known allergy to xylocaine (which is be used as a local anesthetic for the placement of the arterial catheter).

PARKINSON`S DISEASE PATIENTS
1. Subject has parkinsonism not caused by idiopathic Parkinson’s disease (e.g. drug-induced, metabolic disorders, encephalitis, vascular parkinsonism, atypical parkinsonian syndromes such as multiple system atrophy, progressive supranuclear palsy and corticobasal degeneration).
2. Subject has a history of another major neurological disorder or history of significant brain lesion (e.g. tumor, stroke).
3. Subject has significant structural brain lesions on T1 or T2 MRI, unrelated to IPD.
4. Subject has a history of any major disease that may interfere with radiotracer investigations (especially severe liver and kidney disease, or uncontrolled diabetes).
5. Subject is unable to lie sufficiently still in the PET system, or has tremor with significant head movements.
6. Subject consumes excessive alcohol (average > 4 units/day) or has recreational/illicit drug use (including cannabis).
7. Subject chronically uses anti-inflammatory medication including systemic steroids.
8. Subject has known allergy to lidocaine (which may be used as a local anesthetic for the placement of the arterial catheter).
9. Uncontrolled hypertension judged by the investigator. .
10. Previous repetitive use of psychotropic medication.
11. Pregnancy or lactation (only for women).
12. Administration of any investigational product within

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Parkinson´s disease
MedDRA version: 20.0 Level: LLT Classification code 10034007 Term: Parkinson's disease NOS System Organ Class: 100000004852

Intervention(s)

Product Name: (2-chloro-5-[11C]methoxy-N-(((3s,5s,7s)-3,5,7-trifluoroadamantan-1-yl)methyl) benzamide)
Product Code: [11C]SMW139
Pharmaceutical Form: Injection

Primary Outcome(s)

Main Objective: Primary objective: To determine regional binding differences of [11C]SMW139 in 7 PD patients and 7 healthy volunteers.

Secondary Objective: Secondary objectives: Brain kinetics and determination of brain P2X7R availability (VT and BPND) using [11C]SMW139 PET in 7 PD patients and 7 healthy age-matched healthy controls. Correlation between nigro-striatal P2X7R availability measured with using [11C]SMW139 PET and DAT availability measured using [18F]FE-PE2I PET in 7 PD patients and 7 healthy age-matched healthy controls.

Timepoint(s) of evaluation of this end point: The end point will be evaluated after all study procedures in all Parkinson´s disease patients and healthy controls have been completed.

Primary end point(s): Completion of PET imaging of patients with Parkinson´s disease and healthy controls with [11C]SMW139

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: The end point will be evaluated after all study procedures in all Parkinson´s disease patients and healthy controls have been completed.

Secondary end point(s): Completion of study procedures other than PET imaging of patients with Parkinson´s disease and healthy controls with [11C]SMW139

Secondary ID(s)

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