Clinical trial NCT05340660: mGluR5 Imaging in ALS Using PET
Official title: Metabotropic Glutamate Receptor 5 Imaging in Amyotrophic Lateral Sclerosis Using Positron Emission Tomography
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Amyotrophic Lateral Sclerosis
Keywords: Receptor, Metabotropic Glutamate 5
Brain / diagnostic imaging
Positron-Emission Tomography / methods
Radiopharmaceuticals / pharmacokinetics*
PSS232
Humans
Adult
Lead sponsor: Cantonal Hospital of St. Gallen
Sponsor class: OTHER
Collaborators: name: University of Zurich
name: ETH Zurich
First posted: 2022-04-22
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline in [18F]PSS232 uptake in the brain and spinal cord in ALS patients at 6 months
timeFrame: Baseline and 6 months
Secondary outcomes:
measure: Difference of [18F]PSS232 uptake in the brain and spinal cord between ALS patients and healthy, age and gender-matched subjects.
timeFrame: 6 months
measure: Correlation of change from baseline of [18F]PSS232 uptake with change from baseline of ALSFRS-R Score at day 180
timeFrame: 6 months
measure: 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
timeFrame: 6 months
measure: Correlation of change from baseline of [18F]PSS232 uptake with change from baseline of ECAS at day 180
timeFrame: 6 months
Other outcomes:
Locations:
city: St. Gallen
country: Switzerland
facility: Neuromuscular Center/ALS Clinic, Cantonal Hospital St. Gallen
Study officials:
affiliation: Neuromuscular Center/ALS Clinic, Cantonal Hospital St. Gallen, 9007 St. Gallen, Switzerland
name: Nathalie Braun, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: