PsychosisNCT03442101
Trajectories of Treatment Response as Window Into the Heterogeneity of Psychosis: a Longitudinal Multimodal Imaging Study
An observational study of Psychosis, run by University of Alabama at Birmingham at 1 site in United States.
Trial summary
Psychosis is a heterogeneous disorder and present treatment only works for a limited number of patients. In order to identify new therapeutic targets, this study will longitudinally characterize the underlying pathologies in those with poor treatment response using complimentary brain imaging modalities. Read more about this study
- Who is it for?
- Ages 17 to 35 years
- Conditions the study is for
- Psychosis
- What is being tested?
- Patients with psychosis will be treated with known antipsychotic medication
- How many people
- 156 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Apr 2018to 31 Dec 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 17 to 35 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: First episode psychosis subjects
Who may be able to join
- A diagnosis of first episode psychosis
- Never been treated with an antipsychotic medication
- Between the age of 17 and 35
Who cannot join
- Inability to sign informed consent assessed by the Evaluation to sign - - Consent form
- Poorly controlled acute or chronic medical and neurological conditions
- History of head trauma with loss of consciousness for >2 minutes
- Clinically significant depression, hypomania, or mania
- Active substance abuse or dependence (except for nicotine)
- Suspected substance-induced psychosis
- Treatment with drugs known to affect brain glutamate levels
- Pregnant females
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Trajectories of Treatment Response as Window Into the Heterogeneity of Psychosis: a Longitudinal Multimodal Imaging Study in Medication-naïve First Episode Psychosis Patients
Psychosis is a heterogeneous disorder and present treatment only works for a limited number of patients. In order to identify new therapeutic targets, this study will longitudinally characterize the underlying pathologies in those with poor treatment response using complimentary brain imaging modalities.
Read the detailed description
Schizophrenia is a heterogeneous disorder that likely involves multiple underlying pathological mechanisms, which has plagued attempts to identify rational therapeutic targets. All available antipsychotic drugs (APD) are dopamine receptor antagonists, but clinical response is variable, with a third of patients being partial responders, and a third non-responders. Arguably, those who respond well to APD have primarily dopaminergic abnormalities but it is imperative to also characterize the specific underlying pathologies in those with poor response in order to unravel the heterogeneity of psychosis and effectively develop new treatments. The investigators propose to longitudinally follow treatment response to APD for eight months in medication-naïve first episode psychosis (FEP) subjects using complementary brain imaging techniques.
The investigators have already identified provisional markers for several different pathophysiological mechanisms underlying psychosis, including abnormalities in glutamate, brain connectivity, and neurodevelopment that they can track with brain imaging. In addition, the investigators propose to study the changes that occur in the brain in early compared to delayed treatment responders and changes that occur over time in response to treatment. By characterizing treatment trajectories and their relationship to baseline pathophysiologic alterations, the investigators will further complement their mechanistic understanding of the heterogeneity of psychosis.
The investigators propose to study 117 well-characterized FEP subjects who are medication naïve and treat them with the most frequently used APD for 32 weeks. The investigators will follow a rigorous longitudinal design to capture treatment response whereby those without an adequate response after 16 weeks of treatment will be switched to another APD for 16 weeks. All patients will be scanned four times: at baseline and after 6, 16, and 32 weeks of treatment. The investigators will use (1) proton MR Spectroscopy (MRS), (2) task and resting state functional MRI and (3) MRI and diffusion weighted imaging (DWI) to measure brain biochemistry, function and structure. Using several imaging modalities has the potential to interrogate different neurobiological aspects of treatment response and will offer greater opportunities for clustering the patterns and combinations of the underlying pathologies in those with poor response.
Deconstructing the heterogeneity of psychosis has broad implications for the identification of specific targets for drug development, and to lay the groundwork needed to conduct therapeutic trials on patients characterized by their specific underlying psychopathology.
- Conditions
- Psychosis
- Being tested
- Patients with psychosis will be treated with known antipsychotic medication
- Medical subject headings
- Psychotic Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Patients with psychosis will be treated with known antipsychotic medicationDrug
Also called Brain imaging scans will be obtained 4 times during the study
Subjects with first episode psychosis will be treated with risperidone, the most frequently used antipsychotic drug (APD) for 32 weeks. The study will follow a rigorous longitudinal design to capture treatment response whereby those without an adequate response after 16 weeks of treatment will be switched to aripiprazole, another APD for 16 weeks. All patients will be scanned four times: at baseline and after 6, 16, and 32 weeks of treatment.
| Study group | Role | What they receive |
|---|---|---|
| Treatment group | These participants are newly diagnosed with psychosis. Receives: Drug: Patients with psychosis will be treated with known antipsychotic medication |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measures of brain structure
Measures of brain structure, as measured with diffusion tensor imaging (DTI) that are associated at baseline (when patients are unmedicated) with subsequent treatment response to antipsychotic medication.
Measured: 32 weeks
Measures of brain function
Measures of brain function, as measured with functional MRI (fMRI) that are associated at baseline (when patients are unmedicated) with subsequent treatment response to antipsychotic medication.
Measured: 32 weeks
Measures of brain biochemistry
Measures of brain biochemistry, as measured with MR Spectroscopy, that are associated at baseline (when patients are unmedicated) with subsequent treatment response to antipsychotic medication.
Measured: 32 weeks
Secondary outcomes (3)
Changes in measures of brain structure
Changes in measures of brain structure over time that are associated with treatment response to antipsychotic medication.
Measured: 32 weeks
Changes in measures of brain function
Changes in measures of brain function over time that are associated with treatment response to antipsychotic medication.
Measured: 32 weeks
Changes in measures of brain biochemistry
Changes in measures of brain biochemistry over time that are associated with treatment response to antipsychotic medication.
Measured: 32 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Feb 2018
- Study start1 Apr 2018
- Primary completion30 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for PsychosisStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 156 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Dr. Adrianne C Lahti, University of Alabama at Birmingham
- Investigators
- Adrienne Lahti, MD, Principal investigator, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03442101
- Sponsor's protocol ID
- IRB-300000959
- Other IDs
- R01MH113800
- Status last verified
- Dec 2025
- First submitted
- 9 Feb 2018
- Last updated
- 12 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Maximo JO, Richman J, Lahti AC. Trajectories of psychotic symptoms and fronto-parietal resting state functional connectivity MRI following an antipsychotic trial in medication-naive first-episode psychosis patients. Neuropsychopharmacology. 2026 Aug 21. doi: 10.1038/s41386-026-02515-x. Online ahead of print.
PubMed 42629434Maximo JO, Briend F, Armstrong WP, Kraguljac NV, Lahti AC. Salience network glutamate and brain connectivity in medication-naive first episode patients - A multimodal magnetic resonance spectroscopy and resting state functional connectivity MRI study. Neuroimage Clin. 2021;32:102845. doi: 10.1016/j.nicl.2021.102845. Epub 2021 Sep 29.
PubMed 34662778Maximo JO, Nelson EA, Armstrong WP, Kraguljac NV, Lahti AC. Duration of Untreated Psychosis Correlates With Brain Connectivity and Morphology in Medication-Naive Patients With First-Episode Psychosis. Biol Psychiatry Cogn Neurosci Neuroimaging. 2020 Feb;5(2):231-238. doi: 10.1016/j.bpsc.2019.10.014. Epub 2019 Nov 9.
PubMed 31902581
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Trajectories of Treatment Response as Window Into the Heterogeneity of Psychosis: a Longitudinal Multimodal Imaging Study in Medication-naïve First Episode Psychosis Patients
- ClinicalTrials.gov ID
- NCT03442101
- Acronym / sponsor ID
- IRB-300000959
- Conditions
- Psychosis
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 156 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 1 Apr 2018 (actual)
- Primary completion
- 30 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 22 Feb 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Psychosis is a heterogeneous disorder and present treatment only works for a limited number of patients. In order to identify new therapeutic targets, this study will longitudinally characterize the underlying pathologies in those with poor treatment response using complimentary brain imaging modalities.
Detailed description
Schizophrenia is a heterogeneous disorder that likely involves multiple underlying pathological mechanisms, which has plagued attempts to identify rational therapeutic targets. All available antipsychotic drugs (APD) are dopamine receptor antagonists, but clinical response is variable, with a third of patients being partial responders, and a third non-responders. Arguably, those who respond well to APD have primarily dopaminergic abnormalities but it is imperative to also characterize the specific underlying pathologies in those with poor response in order to unravel the heterogeneity of psychosis and effectively develop new treatments. The investigators propose to longitudinally follow treatment response to APD for eight months in medication-naïve first episode psychosis (FEP) subjects using complementary brain imaging techniques.
The investigators have already identified provisional markers for several different pathophysiological mechanisms underlying psychosis, including abnormalities in glutamate, brain connectivity, and neurodevelopment that they can track with brain imaging. In addition, the investigators propose to study the changes that occur in the brain in early compared to delayed treatment responders and changes that occur over time in response to treatment. By characterizing treatment trajectories and their relationship to baseline pathophysiologic alterations, the investigators will further complement their mechanistic understanding of the heterogeneity of psychosis.
The investigators propose to study 117 well-characterized FEP subjects who are medication naïve and treat them with the most frequently used APD for 32 weeks. The investigators will follow a rigorous longitudinal design to capture treatment response whereby those without an adequate response after 16 weeks of treatment will be switched to another APD for 16 weeks. All patients will be scanned four times: at baseline and after 6, 16, and 32 weeks of treatment. The investigators will use (1) proton MR Spectroscopy (MRS), (2) task and resting state functional MRI and (3) MRI and diffusion weighted imaging (DWI) to measure brain biochemistry, function and structure. Using several imaging modalities has the potential to interrogate different neurobiological aspects of treatment response and will offer greater opportunities for clustering the patterns and combinations of the underlying pathologies in those with poor response.
Deconstructing the heterogeneity of psychosis has broad implications for the identification of specific targets for drug development, and to lay the groundwork needed to conduct therapeutic trials on patients characterized by their specific underlying psychopathology.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment group | – | Drug: Patients with psychosis will be treated with known antipsychotic medicationThese participants are newly diagnosed with psychosis. |
Who may qualify
- Ages
- 17 to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- First episode psychosis subjects
Key inclusion criteria (3 listed)
- A diagnosis of first episode psychosis
- Never been treated with an antipsychotic medication
- Between the age of 17 and 35
Key exclusion criteria (8 listed)
- Inability to sign informed consent assessed by the Evaluation to sign - - Consent form
- Poorly controlled acute or chronic medical and neurological conditions
- History of head trauma with loss of consciousness for >2 minutes
- Clinically significant depression, hypomania, or mania
- Active substance abuse or dependence (except for nicotine)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Patients with psychosis will be treated with known antipsychotic medicationAlso: Brain imaging scans will be obtained 4 times during the studySubjects with first episode psychosis will be treated with risperidone, the most frequently used antipsychotic drug (APD) for 32 weeks. The study will follow a rigorous longitudinal design to capture treatment response whereby those without an adequate response after 16 weeks of treatment will be switched to aripiprazole, another APD for 16 weeks. All patients will be scanned four times: at baseline and after 6, 16, and 32 weeks of treatment. | Drug | Treatment group |
Primary outcome
Measures of brain structure
Time frame: 32 weeks
Measures of brain structure, as measured with diffusion tensor imaging (DTI) that are associated at baseline (when patients are unmedicated) with subsequent treatment response to antipsychotic medication.
Measures of brain function
Time frame: 32 weeks
Measures of brain function, as measured with functional MRI (fMRI) that are associated at baseline (when patients are unmedicated) with subsequent treatment response to antipsychotic medication.
Measures of brain biochemistry
Time frame: 32 weeks
Measures of brain biochemistry, as measured with MR Spectroscopy, that are associated at baseline (when patients are unmedicated) with subsequent treatment response to antipsychotic medication.
3 secondary outcomes
Changes in measures of brain structure
Time frame: 32 weeks
Changes in measures of brain function
Time frame: 32 weeks
Changes in measures of brain biochemistry
Time frame: 32 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2026.
- Derived from this study: PubMed 42629434Maximo JO, Richman J, Lahti AC. Trajectories of psychotic symptoms and fronto-parietal resting state functional connectivity MRI following an antipsychotic trial in medication-naive first-episode psychosis patients. Neuropsychopharmacology. 2026 Aug 21. doi: 10.1038/s41386-026-02515-x. Online ahead of print.
- Derived from this study: PubMed 34662778Maximo JO, Briend F, Armstrong WP, Kraguljac NV, Lahti AC. Salience network glutamate and brain connectivity in medication-naive first episode patients - A multimodal magnetic resonance spectroscopy and resting state functional connectivity MRI study. Neuroimage Clin. 2021;32:102845. doi: 10.1016/j.nicl.2021.102845. Epub 2021 Sep 29.
- Derived from this study: PubMed 31902581Maximo JO, Nelson EA, Armstrong WP, Kraguljac NV, Lahti AC. Duration of Untreated Psychosis Correlates With Brain Connectivity and Morphology in Medication-Naive Patients With First-Episode Psychosis. Biol Psychiatry Cogn Neurosci Neuroimaging. 2020 Feb;5(2):231-238. doi: 10.1016/j.bpsc.2019.10.014. Epub 2019 Nov 9.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Adrienne Lahti, MD principal investigator
University of Alabama at Birmingham
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Psychosis, run by University of Alabama at Birmingham at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 12 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Measures of brain structure (time frame: 32 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03442101, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jan 2026.