mGluR5 Imaging in ALS Using PET

Amyotrophic Lateral Sclerosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05340660
• Other study ID #: BASEC Nr. 2021-01044
• Status: Recruiting
• Phase: N/A
• Start date: April 2022
• Est. completion date: April 2025

Study information

• Verified date: April 2022
• Source: Cantonal Hospital of St. Gallen
• Contact: Nathalie Braun, MD, PhD
• Phone: +41 71 494 35 81
• Email: nathalie.braun[@]kssg.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: April 2025
• Est. primary completion date: October 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Intervention

Radiation:
• [ 18 F]PSS232
[ 18 F]PSS232 for imaging metabotropic glutamate receptor subtype 5 and comparing expression of the receptor in healthy persons and ALS patients

Locations

Country	Name	City	State
Switzerland	Neuromuscular Center/ALS Clinic, Cantonal Hospital St. Gallen	St. Gallen

Sponsors (3)

Lead Sponsor	Collaborator
Nathalie Braun	ETH Zurich, University of Zurich

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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