mGluR5 Imaging in ALS Using PET

Study Overview
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Brief Summary
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In ALS models, it was shown that receptors, that bind an important messenger substance (glutamate) in the brain, are increased. In this research project, the investigators want to use a specific radioactive substance to find out whether these receptors are more detectable in people with ALS than in healthy people and increase over the course of the disease.

Detailed Description
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With this study, the investigators want to examine whether receptors (docking points on the surface of a nerve cell) that bind an important messenger substance in the brain (glutamate) are increased in patients with amyotrophic lateral sclerosis (ALS) as the disease progresses. Based on observations from ALS models, the investigators suspect that this increase in receptors contributes to the damage to the nerve cells in ALS. To image these receptors, the investigators use a specific radioactive substance and imaging combining positron emission tomography (PET), magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) of the brain and spinal cord. The investigators will examine healthy people and ALS patients. The reason is that little is known about the receptor, even in healthy people. The investigators also do not know if and when the receptor is increasingly detectable in the course of the ALS disease. Only by comparing diseased and healthy people it can be determined if and when the receptor is built up in ALS patients. The investigators also hope to gain more information, e.g. about the distribution of receptors in the brain of healthy people compared to patients.

Official Title
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Metabotropic Glutamate Receptor 5 Imaging in Amyotrophic Lateral Sclerosis Using Positron Emission Tomography

Conditions
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Amyotrophic Lateral Sclerosis

Intervention / Treatment
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* Radiation: [ 18 F]PSS232


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinically probable, probable laboratory supported, or definite ALS according to the revised version of the El Escorial World Federation of Neurology criteria (EEC) (45) Disease duration ≤18 months Pre-study ALSFRS-R progression between disease onset and screening of - 0.4 points/month or worse (calculated by ALSFRS -R total score decline form 48 divided by the months since onset of ALS symptoms) Upright slow vital capacity (sVC) ≥65 % of normal (best of three measurements) Exclusion Criteria : Previous participation in another clinical study involving trial medication within the preceding 12 weeks History or presence of significant psychiatric disease, such as depression, evaluated with the ALS depression questionnaire (ADI-12) ≥ 23 (43) since depression has an impact on mGluR5 expression (44) Use of tobacco, including cigarettes, smokeless tobacco, cigars, and pipes; Ex- smoker having quit smoking ≥ 2 years

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ALS Patient<br> | Radiation: [ 18 F]PSS232<br>* [ 18 F]PSS232 for imaging metabotropic glutamate receptor subtype 5 and comparing expression of the receptor in healthy persons and ALS patients<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in [18F]PSS232 uptake in the brain and spinal cord in ALS patients at 6 months | Difference of [18F]PSS232 uptake in the brain and spinal cord of ALS patients at baseline and day 180, as assessed by PET and MRI to allow morphological mapping. | Baseline and 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference of [18F]PSS232 uptake in the brain and spinal cord between ALS patients and healthy, age and gender-matched subjects. | Difference of [18F]PSS232 uptake in the brain and spinal cord of ALS patients and healthy subjects at baseline and day 180, as assessed by PET and MRI to allow morphological mapping | 6 months | 
| Correlation of change from baseline of [18F]PSS232 uptake with change from baseline of ALSFRS-R Score at day 180 | Change from baseline to day 180 in [18F]PSS232 uptake in the brain and spinal cord in ALS patients will be correlated to change from baseline to 180d in the ALS Functional Rating Scale (ALSFRS-R), evaluating bulbar, respiratory, upper limb and lower limb function with a total score of 48 (minimal value 0, maximal value 48, higher scores mean a better outcome). | 6 months | 
| Correlation of change from baseline of [18F]PSS232 uptake with change from baseline of respiratory function, as measuerd by slow vital capacity (sVC) and sniff nasal inspiratory pressure (SNIP) at day 180 | Change from baseline to day 180 in [18F]PSS232 uptake in the brain and spinal cord in ALS patients will be correlated to change from baseline to 180d in respiratory function, as measured by slow vital capacity (sVC) and sniff nasal inspiratory pressure (SNIP). | 6 months | 
| Correlation of change from baseline of [18F]PSS232 uptake with change from baseline of ECAS at day 180 | Change from baseline to day 180 in [18F]PSS232 uptake in the brain and spinal cord in ALS patients will be correlated to change from baseline to 180d in cognitive and behavioral function, as assessed by Edinburgh cognitive and behavioral ALS Screen (ECAS, minimal value 0, maximal value 136, higher scores mean a better outcome). | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Receptor, Metabotropic Glutamate 5, Brain / diagnostic imaging, Positron-Emission Tomography / methods, Radiopharmaceuticals / pharmacokinetics*, PSS232, Humans, Adult