tDCS for Schizophrenia

Overseen By Ariel Graff, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Centre for Addiction and Mental Health

Must be taking: Oral antipsychotics

Must not be taking: Levetiracetam, Anticoagulants

Disqualifiers: Seizures, Substance dependence, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates whether transcranial direct current stimulation (tDCS), a brain stimulation technique, can alter brain connections in people with schizophrenia. Researchers will use a special scan with [18F]SDM-8, a radiotracer for brain imaging, to examine brain activity and connections. This trial is part of a larger study exploring how this treatment might help individuals adhere to their medication. People with schizophrenia or schizoaffective disorder, already participating in a related study and on a stable medication schedule for at least two months, might be suitable candidates.

As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in schizophrenia treatment.

Will I have to stop taking my current medications?

The trial requires that you stay on a stable dose of your current oral antipsychotic and other medications for at least 2 months before joining, and you should not expect changes in your medication dose during the study.

What prior data suggests that this method is safe for measuring synaptic density in humans?

Research has shown that [18F]SDM-8 is a promising tool for measuring brain activity. This substance aids PET scans in visualizing brain function. Studies have found that [18F]SDM-8 remains stable for hours and is safe for human use, indicating it is well-tolerated for imaging.

No specific reports of side effects from [18F]SDM-8 have emerged, and its use in other human studies without major issues is reassuring. However, it is important to remember that this is a tool for imaging, not a treatment. It assists in diagnosing or studying conditions. Always consult a doctor before joining a trial to understand the risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about [18F]SDM-8 because it could provide a new way to understand and treat schizophrenia. Unlike standard treatments that primarily focus on managing symptoms through antipsychotic medications, this approach involves transcranial direct current stimulation (tDCS) to potentially alter synaptic density in the brain. This unique mechanism targets the brain's connectivity and function more directly, offering hope for a deeper impact on the underlying brain changes associated with schizophrenia. If successful, it could lead to more precise and effective therapies for patients with this challenging condition.

What evidence suggests that transcranial direct current stimulation (tDCS) is effective for schizophrenia?

Research has shown that [18F]SDM-8 is a promising tool for measuring the density of connections between brain cells. These connections are crucial for communication among brain cells. In animal studies, [18F]SDM-8 has effectively demonstrated changes in these connections, a key concern in conditions like schizophrenia. This PET radiotracer, used in brain scans, provides the clearest images of these connections. Although it does not directly treat schizophrenia, it aids researchers in understanding how treatments like transcranial direct current stimulation (tDCS) might affect the brain. Participants in this trial will include those with Schizophrenia/Schizoaffective Disorder, currently enrolled in the tDCS-adherence parent study. ^{1 2 3 6 7}

Who Is on the Research Team?

Philip Gerretsen, MD, PhD

Principal Investigator

Centre for Addiction and Mental Health

Are You a Good Fit for This Trial?

Inclusion Criteria

Male or female participants of any race or ethnicity

DSM-V diagnosis of schizophrenia or schizoaffective disorder

Capable of consenting to participate in the research study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 visit (in-person)

Baseline PET Scan

Participants undergo a PET scan to measure baseline synaptic density levels using the ]SDM-8 tracer

1 day

1 visit (in-person)

tDCS Treatment

Participants receive 2 weeks of tDCS treatment under the parent study protocol

2 weeks

Post-treatment PET Scan

Participants undergo a second PET scan to measure changes in synaptic density levels after tDCS treatment

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• [18F]SDM-8

How Is the Trial Designed?

Group I: Schizophrenia/Schizoaffective Disorder Experimental Treatment 1 Intervention

Participants with Schizophrenia/Schizoaffective Disorder and currently enrolled in the tDCS-adherence parent study (REB# 103-2018).

Who Is Running the Clinical Trial?

Centre for Addiction and Mental Health

Lead Sponsor

Trials

388

Recruited

84,200+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6810685/

Synthesis and in Vivo Evaluation of a Novel PET Radiotracer ... 18 F-SDM-8 holds promise as an excellent radiotracer for SV2A and as a biomarker for synaptic density measurement in neurodegenerative diseases and psychiatric ...

2. jnm.snmjournals.org jnm.snmjournals.org/content/63/supplement_1/60s

Imaging of Synaptic Density in Neurodegenerative Disorders Mouse and rat models of neurodegenerative diseases have been studied with small-animal PET, providing validation by comparison to direct tissue ...

3. ejnmmipharmchem.springeropen.com ejnmmipharmchem.springeropen.com/articles/10.1186/s41181-024-00284-w

GMP-compliant automated radiosynthesis of [18F] SynVesT-1 ... These radiotracers were developed many years ago and have been used on either an intermediate to widespread basis in PET imaging studies.

4. researchgate.net researchgate.net/publication/363159171_GMP_Production_of_18_FSynVesT-1_a_Radioligand_for_in_vivo_PET_Imaging_of_Synaptic_Vesicle_Glycoprotein_2A

GMP Production of [ 18 F]SynVesT‐1, a Radioligand for in ... We developed a new tracer, an 18F-labeled difluoro-analog of UCB-J (18F-SynVesT-1, a.k.a. 18F-SDM-8), which displayed favorable properties in monkeys. ... 18F- ...

5. biorxiv.org biorxiv.org/content/10.1101/2021.06.25.449978v1.full

A metabolically stable PET tracer for imaging synaptic ... We have successfully synthesized a metabolically stable and high affinity SV2A PET tracer, [ 18 F]SDM-16, which showed high specific and reversible binding in ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11387577/

GMP-compliant automated radiosynthesis of [18F] ... Among them, the fluorine-18-labeled radioligand [18F] SynVesT-1 (also known as [18F] SDM-8 or [18F] MNI-1126), developed by the Yale PET Center, has shown the ...

7. mdpi.com mdpi.com/1420-3049/25/10/2303

The Rise of Synaptic Density PET Imaging This compound was initially named [18F]SDM-8 by the Yale University ... 18f-Labeled Ligand ([18f]Ucb-H). J. Med. Chem. 2016, 59, 8955–8966. [Google ...