A Multimodal Imaging Study of Dopamine in Early Psychosis

NCT06977308 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 83611R01MH128330
• Study Type: interventional
• Target: 115
• Locations: 0 countries
• Sites: N/A

Brief Summary

The development of new treatments for psychosis, a psychiatric condition that is prevalent and highly disabling despite antipsychotic medications, has been limited, in part, by a lack of information from brain imaging studies during the period that leads to the development of psychotic symptoms. In this project the investigators will use Positron Emission Tomography (PET) and neuromelanin-sensitive magnetic resonance imaging (NM-MRI) to examine a brain chemical that is involved in schizophrenia called dopamine and where it first becomes abnormal. The investigators will use multimodal PET/MR imaging (i.e., \[11C\]raclopride w/MPH challenge and NM-MRI) in the same CHR patients. The investigators will recruit 115 clinical high risk individuals. All subjects will undergo \[11C\]raclopride w/methylphenidate challenge and neuromelanin-MRI imaging along with clinical assessments. Patients will be followed every 3 months for two years or until conversion to psychosis, whichever comes first, to assess for conversion to psychosis and clinical outcomes.

Conditions

Clinical High Risk for Psychosis (CHR)

Keywords

clinical high risk for psychosis

Outcome Measures

Primary Outcomes (2)

• Dopamine transmission

  Delta BPND of \[11C\]raclopride in the Associative Striatum

  From the first (before methylphenidate) to the second PET scans (one hour after methylphenidate) on Day 1 of the study

• Conversion to syndromal psychosis

  Development of a '6' on a P symptom of the SIPS

  From administration of the study drug to either conversion to a syndromal psychotic disorder or 24 months, whichever comes first.

Secondary Outcomes (3)

• Positive Symptoms

  At time zero before administration of methylphenidate

• Negative Symptoms

  At time zero before administration of methylphenidate

• Dopamine Transmission in the ventral striatum

  From the first (before methylphenidate) to the second PET scans (one hour after methylphenidate) on Day 1 of the study

Other Outcomes (3)

• Baseline dopamine

  At time zero before administration of methylphenidate

• Change in positive symptoms

  From time zero before administration of methylphenidate to either conversion to a syndromal psychotic disorder or 24 months, whichever comes first.

• Change in negative symptoms

  From time zero before administration of methylphenidate to either conversion to a syndromal psychotic disorder or 24 months, whichever comes first.

Study Arms (1)

Methylphenidate

EXPERIMENTAL

Each subject will receive one oral dose of 60mg methylphenidate in between 2 PET scans with \[11C\]raclopride.

Drug: Methylphenidate (MPH); Drug: [11C]raclopride

Interventions

Methylphenidate (MPH) DRUG

Each participate will receive one oral dose of 60mg methylphenidate.

Methylphenidate

[11C]raclopride DRUG

This is the radiotracer that will be used along with methylphenidate to quantify dopamine transmission in this study. It is experimental and used for imaging purposes.

Methylphenidate

Eligibility Criteria

• Age: 18 Years - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Males or females between 18 and 30 years old
• Capacity to give informed consent
• Clinical High Risk (i.e., APSS, GRDS, BIPS)
• Antipsychotic free for 3 weeks before the PET scan
• Clinically stable enough for the study

You may not qualify if:

• Any substance use disorder, of any severity, within the previous month (before PET scan; not including nicotine or caffeine)
• Any current use of substance of abuse besides THC/marijuana/cannabis/nicotine/caffeine (on day of PET only)
• Daily tobacco use
• Pregnancy
• Lactation
• Presence of insulin-dependent diabetes
• IQ \< 70 (i.e., WTAR \< 6)
• Acute risk for suicide (i.e., score of 4-5 within the previous month or 6 within the previous 3 months on the CSSRS) or violence, or history of severe violent behavior that may be exacerbated by methylphenidate
• Presence of metallic objects in the body
• Lifetime exposure to radiation in the workplace (i.e., being badged for radiation exposure), or exposure to radiation in the context of research protocol within the previous year that exceeds annual limits
• More than one risk factor for coronary artery disease (e.g., smoking, hyperlipidemia, sedentary lifestyle)
• Hypertension
• Presence of clinically significant brain abnormalities. \[For PET Scan Only\]
• Previous adverse reaction to stimulants that would preclude receiving methylphenidate
• Presence or positive history of any cardiovascular disease, medical or neurological condition that would preclude methylphenidate administration or participation in this study

Sponsors & Collaborators

• New York State Psychiatric Institute: lead
• National Institute of Mental Health (NIMH): collaborator
• Columbia University Irving Medical Centre: collaborator
• Research Foundation for Mental Hygiene, Inc. / Columbia University: collaborator
• Stony Brook Medicine: collaborator

Related Publications (1)

• Girgis RR, Slifstein M, Brucato G, Kegeles LS, Colibazzi T, Lieberman JA, Abi-Dargham A. Imaging synaptic dopamine availability in individuals at clinical high-risk for psychosis: a [11C]-(+)-PHNO PET with methylphenidate challenge study. Mol Psychiatry. 2021 Jun;26(6):2504-2513. doi: 10.1038/s41380-020-00934-w. Epub 2020 Nov 5.

  PMID: 33154566 BACKGROUND

MeSH Terms

Interventions

Methylphenidate

Intervention Hierarchy (Ancestors)

Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Ragy Girgis, MD

CONTACT

646-774-5553; ragy.girgis@nyspi.columbia.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Clinical Psychiatry

Study Record Dates

• First Submitted: May 8, 2025
• First Posted: May 18, 2025
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): October 1, 2029
• Study Completion (Estimated): October 1, 2030
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Time Frame: Data will be shared after the study has been completed, as per NIH guidelines.