mGluR5 Imaging in ALS Using PET

• ClinicalTrials.gov Identifier: NCT05340660
• Recruitment Status: Recruiting
• First Posted: April 22, 2022
• Last Update Posted: April 22, 2022
• Sponsor: Nathalie Braun
• Collaborators: University of Zurich; ETH Zurich
• Information provided by (Responsible Party): Nathalie Braun, Cantonal Hospital of St. Gallen

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Amyotrophic Lateral Sclerosis	Radiation: [ 18 F]PSS232	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Metabotropic Glutamate Receptor 5 Imaging in Amyotrophic Lateral Sclerosis Using Positron Emission Tomography
• Estimated Study Start Date: April 2022
• Estimated Primary Completion Date: October 2022
• Estimated Study Completion Date: April 2025

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Change from baseline in [18F]PSS232 uptake in the brain and spinal cord in ALS patients at 6 months [ Time Frame: Baseline and 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.

Secondary Outcome Measures :

1. Difference of [18F]PSS232 uptake in the brain and spinal cord between ALS patients and healthy, age and gender-matched subjects. [ Time Frame: 6 months ]
   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
2. Correlation of change from baseline of [18F]PSS232 uptake with change from baseline of ALSFRS-R Score at day 180 [ Time Frame: 6 months ]
   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).
3. 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 [ Time Frame: 6 months ]
   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).
4. Correlation of change from baseline of [18F]PSS232 uptake with change from baseline of ECAS at day 180 [ Time Frame: 6 months ]
   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).

Eligibility Criteria

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

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

Contacts and Locations

Contacts

Contact: Nathalie Braun, MD, PhD; +41 71 494 35 81; nathalie.braun@kssg.ch

Contact: Zylfije Dibrani; +41 71 494 35 81; Zylfije.Dibrani@kssg.ch

Locations

Switzerland

Neuromuscular Center/ALS Clinic, Cantonal Hospital St. Gallen; Recruiting

St. Gallen, Switzerland, 9007

Contact: Nathalie Braun, MD, PhD +41714943581 nathalie.braun@kssg.ch

Contact: Zylifije Dibrani +41714943581 zylfije.dibrani@kssg.ch

Principal Investigator: Nathalie Braun, MD, PhD

Sponsors and Collaborators

Nathalie Braun

University of Zurich

ETH Zurich

Investigators

• Principal Investigator: Nathalie Braun, MD, PhD; Neuromuscular Center/ALS Clinic, Cantonal Hospital St. Gallen, 9007 St. Gallen, Switzerland

More Information

• Responsible Party: Nathalie Braun, Principal Investigator, Cantonal Hospital of St. Gallen
• ClinicalTrials.gov Identifier: NCT05340660
• Other Study ID Numbers: BASEC Nr. 2021-01044
• First Posted: April 22, 2022
• Last Update Posted: April 22, 2022
• Last Verified: April 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Nathalie Braun, Cantonal Hospital of St. Gallen:

Receptor, Metabotropic Glutamate 5; Brain / diagnostic imaging; Positron-Emission Tomography / methods; Radiopharmaceuticals / pharmacokinetics*; PSS232; Humans; Adult

Additional relevant MeSH terms:

Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Sclerosis; Pathologic Processes; Neurodegenerative Diseases; Nervous System Diseases; Neuromuscular Diseases; Spinal Cord Diseases; Central Nervous System Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases