Study of [11C]CPPC as a Clinical PET Radioligand Biomarker of Microglial Activation in ALS

Phase 1

Not yet recruiting

• Conditions: ALS
• Interventions: Drug: [11C]CPPC PET ligand

• Registration Number: NCT05602142
• Lead Sponsor: Johns Hopkins University

Brief Summary

1. Establish the safety and tolerability of the 5-cyano-N-(4-(4-\[11C\]Methylpiperazin-1-yl)-2-(Piperidin-1-yl)Phenyl)Furan-2-carboxamide (\[11C\]CPPC) PET radioligand in ALS patients and controls

2. Examine whether \[11C\]CPPC PET uptake is elevated in brains of ALS patients and whether there is a correlation with clinical phenotype.

3. Correlate \[11C\]CPPC PET imaging with other ALS outcome measures and biofluid biomarkers

4. Examine longitudinal changes in \[11C\]CPPC PET imaging during disease course.

Detailed Description

There are a paucity of reliable serum and cerebrospinal (CSF) biomarkers and validated neuroimaging techniques to aid in amyotrophic lateral sclerosis (ALS) diagnosis, prognosis, or pharmacodynamic insight. Positron emission tomography (PET) imaging is a technique that uses radioactive molecules attached to a ligand of interest which localizes to the desired target, allowing for visualization of the three dimensional distribution of the ligand's target receptor.

One of the upstream processes that are thought to lead to motor neuron degeneration in ALS is microglial dysfunction, resulting in the initiation of neuroinflammatory cascades. Macrophage colony stimulating factor 1 receptor (CSF1R) is found on microglia predominately in the brain, with low levels of expression in neurons and other neural cells, making it a promising target for studying microglial activation.

Given CSF1's potential role in ALS disease progression, and that its receptor (CSF1R) can be directly targeted, ligands binding this receptor are an area of interest for imaging in ALS. \[11C\]CPPC \[5-cyano-N-(4-(4-\[11C\]methylpiperazin-1-yl)-2-(piperidin-1-yl)phenyl)furan-2-carboxamide\], is a positron-emitting, high-affinity ligand that is specific for CSF1R.

The aims of this study are as follows:

1. Establish the safety and tolerability of the \[11C\]CPPC PET radioligand in ALS patients and controls

2. Examine whether \[11C\]CPPC PET uptake is elevated in brains of ALS patients and whether there is a correlation with clinical phenotype.

3. Correlate \[11C\]CPPC PET imaging with other ALS outcome measures and biofluid biomarkers

4. Examine longitudinal changes in \[11C\]CPPC PET imaging during disease course.

Study Timeline

• Study First Submitted: 2022-10-21
• Study First Submitted QC: 2022-10-26
• Study First Posted: 2022-11-01
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-12
• Last Update Posted: 2025-05-14
• Study Start: 2025-08
• Primary Completion: 2026-01
• Study Completion: 2026-07

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

Not provided

Exclusion Criteria

1. Weakness due to causes other than ALS.

2. Receipt of any investigational drug, device or biologic within 10 days of administration of study compound.

3. Use of anti-inflammatory medications, immunosuppressants, or benzodiazepines within 7 days of administration of study compound.

4. Any concomitant medical disease or condition limiting the safety to participate including, but not limited to:

   1. Coagulopathy
   2. Active infection

5. Any condition that the site PI feels may interfere with participation in the study.

6. Inability to provide informed consent as determined by the site PI.

7. Known clinical evidence of frontotemporal dementia.

8. Inadequate family or caregiver support as determined by the site PI.

9. Presence of any of the following conditions:

   1. Current drug abuse or alcoholism
   2. Unstable medical conditions
   3. Unstable psychiatric illness including psychosis and untreated major depression within 90 days of screening

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
[11C]CPPC	[11C]CPPC PET ligand	All participants will receive \[11C\]CPPC which is a radiotracer ligand that specifically binds to CSF1R.

Primary Outcome Measures

Name	Time	Method
Safety of use of [11C]CPPC in patients with ALS as assessed by a change in complete metabolic panel (CMP) test	Baseline and 180 days after scan	Safety of use of \[11C\]CPPC in positron emission tomography (PET) neuroimaging of patients with a diagnosis of ALS. Safety will be assessed by a change in the CMP from baseline that is outside of the normal range.
Safety of use of [11C]CPPC in patients with ALS as assessed by adverse events	Up to 180 days after scan	Safety of use of \[11C\]CPPC in positron emission tomography (PET) neuroimaging of patients with a diagnosis of ALS. Safety will be assessed by number of adverse events during and up to 180 days after the injection
Safety of use of [11C]CPPC in patients with ALS as assessed by a change in neurological status	Baseline and 180 days after scan	Safety of use of \[11C\]CPPC in positron emission tomography (PET) neuroimaging of patients with a diagnosis of ALS. Safety will be assessed by neurological physical exam to determine if there is a change in the findings from baseline.
Safety of use of [11C]CPPC in patients with ALS as assessed by a change in complete blood count (CBC) test	Baseline and 180 days after scan	Safety of use of \[11C\]CPPC in positron emission tomography (PET) neuroimaging of patients with a diagnosis of ALS. Safety will be assessed by monitoring of the complete blood count (CBC) for a change from baseline that is outside of the normal range.

Secondary Outcome Measures

Name	Time	Method
Sensitivity of use of [11C]CPPC as assessed by a radiologist	Up to 180 days after scan	Sensitivity of use of \[11C\]CPPC in PET neuroimaging to detect ALS will be determined by comparing the PET images from patients with ALS with those from healthy controls.