mGluR5 Imaging in ALS Using PET

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

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.

Study Overview

• Status: Recruiting
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Radiation: [ 18 F]PSS232

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.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nathalie Braun, MD, PhD; Phone Number: +41 71 494 35 81; Email: nathalie.braun@kssg.ch
• Study Contact Backup: Name: Zylfije Dibrani; Phone Number: +41 71 494 35 81; Email: Zylfije.Dibrani@kssg.ch

Study Locations

• Switzerland
  • St. Gallen, Switzerland, 9007
    • Recruiting
    • Neuromuscular Center/ALS Clinic, Cantonal Hospital St. Gallen
    • Contact: Nathalie Braun, MD, PhD; Phone Number: +41714943581; Email: nathalie.braun@kssg.ch
    • Contact: Zylifije Dibrani; Phone Number: +41714943581; Email: zylfije.dibrani@kssg.ch
    • Principal Investigator: Nathalie Braun, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ALS Patient	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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Nathalie Braun
• Collaborators: University of Zurich; ETH Zurich
• Investigators: Principal Investigator: Nathalie Braun, MD, PhD, Neuromuscular Center/ALS Clinic, Cantonal Hospital St. Gallen, 9007 St. Gallen, Switzerland

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2022
• Primary Completion (Anticipated): October 1, 2022
• Study Completion (Anticipated): April 1, 2025

Study Registration Dates

• First Submitted: March 29, 2022
• First Submitted That Met QC Criteria: April 19, 2022
• First Posted (Actual): April 22, 2022

Study Record Updates

• Last Update Posted (Actual): April 22, 2022
• Last Update Submitted That Met QC Criteria: April 19, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Humans; Adult; Receptor, Metabotropic Glutamate 5; Brain / diagnostic imaging; Positron-Emission Tomography / methods; Radiopharmaceuticals / pharmacokinetics*; PSS232
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: BASEC Nr. 2021-01044

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No