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

Tracking Information

• First Submitted Date: March 29, 2022
• First Posted Date: April 22, 2022
• Last Update Posted Date: April 22, 2022
• Estimated Study Start Date: April 2022
• Estimated Primary Completion Date: October 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 19, 2022)

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.

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: April 19, 2022)

• 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
• 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).
• 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).
• 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).

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: mGluR5 Imaging in ALS Using PET
• Official Title: Metabotropic Glutamate Receptor 5 Imaging in Amyotrophic Lateral Sclerosis Using Positron Emission Tomography
• 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.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Basic Science
• Condition: Amyotrophic Lateral 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

Study Arms

Experimental: ALS Patient

Intervention: Radiation: [ 18 F]PSS232

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 19, 2022): 30
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: April 2025
• Estimated Primary Completion Date: October 2022 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

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

• Listed Location Countries: Switzerland

Administrative Information

• NCT Number: NCT05340660
• Other Study ID Numbers: BASEC Nr. 2021-01044
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Nathalie Braun, Cantonal Hospital of St. Gallen
• Original Responsible Party: Same as current
• Current Study Sponsor: Nathalie Braun
• Original Study Sponsor: Same as current

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

• PRS Account: Cantonal Hospital of St. Gallen
• Verification Date: April 2022