mGluR5 Imaging in ALS Using PET

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Primary Purpose

Status

Recruiting

Phase

Not Applicable

Locations

Switzerland

Study Type

Interventional

Intervention

[ 18 F]PSS232

About this trial

This is an interventional basic science trial for Amyotrophic Lateral Sclerosis focused on measuring Receptor, Metabotropic Glutamate 5, Brain / diagnostic imaging, Positron-Emission Tomography / methods, Radiopharmaceuticals / pharmacokinetics*, PSS232, Humans, Adult

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Neuromuscular Center/ALS Clinic, Cantonal Hospital St. GallenRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ALS Patient

Arm Description

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

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).

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).

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).

Full Information

NCT ID

NCT05340660

First Posted

March 29, 2022

Last Updated

April 19, 2022

Sponsor

Nathalie Braun

Collaborators

University of Zurich, ETH Zurich

1. Study Identification

Unique Protocol Identification Number

NCT05340660

Brief Title

mGluR5 Imaging in ALS Using PET

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2022

Overall Recruitment Status

Recruiting

Study Start Date

April 2022 (Anticipated)

Primary Completion Date

October 2022 (Anticipated)

Study Completion Date

April 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Nathalie Braun

Collaborators

University of Zurich, ETH Zurich

4. Oversight

Studies a U.S. FDA-regulated Drug Product

No

Studies a U.S. FDA-regulated Device Product

No

Data Monitoring Committee

No

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Amyotrophic Lateral Sclerosis

Keywords

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

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

ALS Patient

Arm Type

Experimental

Intervention Type

Radiation

Intervention Name(s)

[ 18 F]PSS232

Intervention Description

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

Primary Outcome Measure Information:

Title

Change from baseline in [18F]PSS232 uptake in the brain and spinal cord in ALS patients at 6 months

Description

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.

Time Frame

Baseline and 6 months

Secondary Outcome Measure Information:

Title

Difference of [18F]PSS232 uptake in the brain and spinal cord between ALS patients and healthy, age and gender-matched subjects.

Description

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

Time Frame

6 months

Title

Correlation of change from baseline of [18F]PSS232 uptake with change from baseline of ALSFRS-R Score at day 180

Description

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).

Time Frame

6 months

Title

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

Description

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).

Time Frame

6 months

Title

Correlation of change from baseline of [18F]PSS232 uptake with change from baseline of ECAS at day 180

Description

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).

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Nathalie Braun, MD, PhD

Phone

+41 71 494 35 81

Email

nathalie.braun@kssg.ch

First Name & Middle Initial & Last Name or Official Title & Degree

Zylfije Dibrani

Phone

+41 71 494 35 81

Email

Zylfije.Dibrani@kssg.ch

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Nathalie Braun, MD, PhD

Organizational Affiliation

Neuromuscular Center/ALS Clinic, Cantonal Hospital St. Gallen, 9007 St. Gallen, Switzerland

Official's Role

Principal Investigator

Facility Information:

Facility Name

Neuromuscular Center/ALS Clinic, Cantonal Hospital St. Gallen

City

St. Gallen

ZIP/Postal Code

9007

Country

Switzerland

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Nathalie Braun, MD, PhD

Phone

+41714943581

Email

nathalie.braun@kssg.ch

First Name & Middle Initial & Last Name & Degree

Zylifije Dibrani

Phone

+41714943581

Email

zylfije.dibrani@kssg.ch

First Name & Middle Initial & Last Name & Degree

Nathalie Braun, MD, PhD

Amyotrophic Lateral Sclerosis

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial