SchizophreniaDUPNCT02034253
Glutamate, Brain Connectivity and Duration of Untreated Psychosis
An observational study of Schizophrenia and Psychosis, run by University of Alabama at Birmingham at 1 site in United States.
Trial summary
The early stages of schizophrenia are associated with significant decreases in social and intellectual abilities, with more declines in chronic disease. Studies have identified relationships between duration of untreated psychosis (the duration between the onset of positive symptoms and treatment) and worse long term… Read more about this study
- Who is it for?
- Ages 17 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Schizophrenia, Psychosis, Schizoaffective Disorder
- What is being tested?
- Risperidone
- How many people
- 134 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2014to Nov 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
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
- Healthy volunteers accepted
- Child, Adult
Study population: The investigators expect to enroll a total of 67 male and female patients with first episode psychosis and 67 demographic matched controls. Among patients who participate in research at the University of Alabama at Birmingham (UAB) the approximate gender, ethnic and race distribution is 75% male and 25% female; 1% Hispanic and 99% Non-Hispanic; 54% White, 44% Black, and 1% Asian/Pacific Islander. The gender distribution is consistent with that observed in clinical populations with schizophrenia. Persons below the age of 17 and above the age of 35 are excluded to minimize the variance in cognitive functioning or brain connectivity that might be attributable to development rather than diagnosis.
Who may be able to join
- Persons with first episode psychosis
- Healthy controls will be matched to first episode psychosis participants on a one to one basis
Who cannot join
- inability to understand and sign informed consent assessed by the Evaluation to sign Consent form
- diagnosable central nervous system illnesses
- poorly controlled acute or chronic medical conditions aside from psychosis
- history of head trauma with loss of consciousness for > 2 minutes
- active substance abuse or dependence (exclusive of nicotine dependence)
- suspected substance induced psychotic symptoms
- clinically significant symptoms of depression, hypomania, or mania
- patients concomitantly treated with drugs known to affect glutamate, such as: valproate, topiramate, gabapentin, levetiracetam, lamotrigine, lithium, and acamprosate
Trial locations and contacts
1 site in 1 country.
About this study
The early stages of schizophrenia are associated with significant decreases in social and intellectual abilities, with more declines in chronic disease. Studies have identified relationships between duration of untreated psychosis (the duration between the onset of positive symptoms and treatment) and worse long term outcomes. However, the neurobiology of this phenomenon and its implications for response to antipsychotic medications remain poorly understood.
Glutamatergic excess altering brain connectivity might provide an explanation for why those with longer duration of untreated psychosis have worse clinical outcomes. The investigators propose to use neuroimaging to study 67 first episode psychosis subjects before and after sixteen weeks of treatment with risperidone, a common antipsychotic. We will measure (1) glutamate and (2) structural and functional brain connectivity and test the hypotheses that glutamatergic abnormalities are present in first episode patients and that longer duration of untreated psychosis is associated with greater connectivity abnormalities that set the stage for poor response to treatment. 67 demographic-matched controls will also be recruited as a comparison group - healthy controls will not receive antipsychotic medication.
Read more
The investigator's previous studies have made progress in the understanding of abnormalities in the glutamate system and brain connectivity in unmedicated patients with schizophrenia and modulation of these by antipsychotic medication. Two indices of glutamatergic dysfunction have been identified. While antipsychotic medications appear to modulate glutamate, the disturbance in the relationship between metabolites is not restored with treatment. In addition, the investigators found that both structural and functional connectivity abnormalities in unmedicated patients with schizophrenia predict patients' response to treatment.
To the investigator's knowledge, no other group has performed a study that uses a combination of complementary neuroimaging techniques that will allow generating a broad characterization of glutamatergic function and brain connectivity in first episode psychosis and change with treatment. The results of the proposed studies could suggest a mechanism by which the duration of untreated psychosis is associated with poor treatment response which might lead to new interventions to target the illness.
- Conditions
- Schizophrenia, Psychosis, Schizoaffective Disorder
- Being tested
- Risperidone
- Keywords
- duration of untreated psychosis, glutamate, functional connectivity, structural connectivity, schizophrenia, psychosis
- Medical subject headings
- Schizophrenia, Psychotic Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RisperidoneDrug
Also called Risperdal
Patients with psychosis will be provided a 16 week regimen of the antipsychotic drug Risperidone in accordance with standard care.
| Study group | Role | What they receive |
|---|---|---|
| first episode psychosis | Unmedicated first episode psychosis patients that wish to enroll in a 16 week treatment regimen with the drug Risperidone. Receives: Drug: Risperidone | |
| healthy demographic-matched controls | healthy controls will be matched to patients one to one based on: age, smoking status, parental socio-economic status, and gender. Healthy controls must be free from current or past Axis I mental disorders, 1st degree relative current or past Axis I mental disorders, and any other neurological conditions. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Comparison of indices of glutamate as measured by 1H-MRS in unmedicated first episode psychosis patients before and after antipsychotic treatment and with healthy controls.
Measured: Up to 5 years
Secondary outcomes (2)
Comparison of structural and functional brain connectivity in first episode psychosis patients before and after antipsychotic treatment and healthy controls
Structural brain connectivity (using diffusion tensor imaging) and functional brain connectivity (using resting state connectivity) will be compared between healthy controls and first episode psychosis patients. Additionally within first episode psychosis patients duration of untreated psychosis (DUP) will be correlated with both structural and functional brain connectivity to determine the impact of DUP on both metrics of brain connectivity.
Measured: Up to 5 years
Evaluation of the contribution of structural and functional connectivity to eventual antipsychotic treatment response in first episode psychosis patients.
The investigators will evaluate the relationship between both structural brain connectivity (using diffusion tensor imaging) and functional brain connectivity (using resting state connectivity) before treatment and treatment response after 16 weeks of risperidone therapy in first episode psychosis patients.
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2014 (estimated)
- Study startJan 2014
- Primary completionNov 2018
- Study completionNov 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for SchizophreniaStudies 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
- Case-control
- Time perspective
- Prospective
- Enrolment
- 134 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. Adrianne C Lahti, University of Alabama at Birmingham
- Investigators
- Adrienne C. Lahti, MD, Principal investigator, University of Alabama at Birmingham, Department of Psychiatry
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02034253
- Sponsor's protocol ID
- 1R01MH102951
- Acronym
- DUP
- Status last verified
- Jan 2019
- First submitted
- 8 Jan 2014
- Last updated
- 22 Jan 2019
- Results posted
- No
- Data monitoring committee
- 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. Higher-order functional brain networks and anterior cingulate glutamate + glutamine (Glx) in antipsychotic-naive first episode psychosis patients. Transl Psychiatry. 2024 Apr 10;14(1):183. doi: 10.1038/s41398-024-02854-7.
PubMed 38600117Maximo 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 31902581Kraguljac NV, Anthony T, Skidmore FM, Marstrander J, Morgan CJ, Reid MA, White DM, Jindal RD, Melas Skefos NH, Lahti AC. Micro- and Macrostructural White Matter Integrity in Never-Treated and Currently Unmedicated Patients With Schizophrenia and Effects of Short-Term Antipsychotic Treatment. Biol Psychiatry Cogn Neurosci Neuroimaging. 2019 May;4(5):462-471. doi: 10.1016/j.bpsc.2019.01.002. Epub 2019 Jan 23.
PubMed 30852126Sivaraman S, Kraguljac NV, White DM, Morgan CJ, Gonzales SS, Lahti AC. Neurometabolic abnormalities in the associative striatum in antipsychotic-naive first episode psychosis patients. Psychiatry Res Neuroimaging. 2018 Nov 30;281:101-106. doi: 10.1016/j.pscychresns.2018.06.003. Epub 2018 Jun 9.
PubMed 30286325
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Glutamate, Brain Connectivity and Duration of Untreated Psychosis
- ClinicalTrials.gov ID
- NCT02034253
- Acronym / sponsor ID
- DUP / 1R01MH102951
- Conditions
- Schizophrenia, Psychosis, Schizoaffective Disorder
- Keywords
- duration of untreated psychosis, glutamate, functional connectivity, structural connectivity, schizophrenia, psychosis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 134 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Study start
- Jan 2014 (actual)
- Primary completion
- Nov 2018 (actual)
- Study completion
- Nov 2018 (actual)
- First posted
- 13 Jan 2014 (estimated)
- 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.
The early stages of schizophrenia are associated with significant decreases in social and intellectual abilities, with more declines in chronic disease. Studies have identified relationships between duration of untreated psychosis (the duration between the onset of positive symptoms and treatment) and worse long term outcomes. However, the neurobiology of this phenomenon and its implications for response to antipsychotic medications remain poorly understood.
Glutamatergic excess altering brain connectivity might provide an explanation for why those with longer duration of untreated psychosis have worse clinical outcomes. The investigators propose to use neuroimaging to study 67 first episode psychosis subjects before and after sixteen weeks of treatment with risperidone, a common antipsychotic. We will measure (1) glutamate and (2) structural and functional brain connectivity and test the hypotheses that glutamatergic abnormalities are present in first episode patients and that longer duration of untreated psychosis is associated with greater connectivity abnormalities that set the stage for poor response to treatment. 67 demographic-matched controls will also be recruited as a comparison group - healthy controls will not receive antipsychotic medication.
The investigator's previous studies have made progress in the understanding of abnormalities in the glutamate system and brain connectivity in unmedicated patients with schizophrenia and modulation of these by antipsychotic medication. Two indices of glutamatergic dysfunction have been identified. While antipsychotic medications appear to modulate glutamate, the disturbance in the relationship between metabolites is not restored with treatment. In addition, the investigators found that both structural and functional connectivity abnormalities in unmedicated patients with schizophrenia predict patients' response to treatment.
To the investigator's knowledge, no other group has performed a study that uses a combination of complementary neuroimaging techniques that will allow generating a broad characterization of glutamatergic function and brain connectivity in first episode psychosis and change with treatment. The results of the proposed studies could suggest a mechanism by which the duration of untreated psychosis is associated with poor treatment response which might lead to new interventions to target the illness.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| first episode psychosis | – | Drug: RisperidoneUnmedicated first episode psychosis patients that wish to enroll in a 16 week treatment regimen with the drug Risperidone. |
| healthy demographic-matched controls | – | –healthy controls will be matched to patients one to one based on: age, smoking status, parental socio-economic status, and gender. Healthy controls must be free from current or past Axis I mental disorders, 1st degree relative current or past Axis I mental disorders, and any other neurological conditions. |
Who may qualify
- Ages
- 17 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
- Study population
- The investigators expect to enroll a total of 67 male and female patients with first episode psychosis and 67 demographic matched controls. Among patients who participate in research at the University of Alabama at Birmingham (UAB) the approximate gender, ethnic and race distribution is 75% male and 25% female; 1% Hispanic and 99% Non-Hispanic; 54% White, 44% Black, and 1% Asian/Pacific Islander. The gender distribution is consistent with that observed in clinical populations with schizophrenia. Persons below the age of 17 and above the age of 35 are excluded to minimize the variance in cognitive functioning or brain connectivity that might be attributable to development rather than diagnosis.
Key inclusion criteria (2 listed)
- Persons with first episode psychosis
- Healthy controls will be matched to first episode psychosis participants on a one to one basis
Key exclusion criteria (8 listed)
- inability to understand and sign informed consent assessed by the Evaluation to sign Consent form
- diagnosable central nervous system illnesses
- poorly controlled acute or chronic medical conditions aside from psychosis
- history of head trauma with loss of consciousness for > 2 minutes
- active substance abuse or dependence (exclusive of nicotine dependence)
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 |
|---|---|---|
| RisperidoneAlso: RisperdalPatients with psychosis will be provided a 16 week regimen of the antipsychotic drug Risperidone in accordance with standard care. | Drug | first episode psychosis |
Primary outcome
Comparison of indices of glutamate as measured by 1H-MRS in unmedicated first episode psychosis patients before and after antipsychotic treatment and with healthy controls.
Time frame: Up to 5 years
2 secondary outcomes
Comparison of structural and functional brain connectivity in first episode psychosis patients before and after antipsychotic treatment and healthy controls
Time frame: Up to 5 years
Evaluation of the contribution of structural and functional connectivity to eventual antipsychotic treatment response in first episode psychosis patients.
Time frame: Up to 5 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2019.
- 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 38600117Maximo JO, Briend F, Armstrong WP, Kraguljac NV, Lahti AC. Higher-order functional brain networks and anterior cingulate glutamate + glutamine (Glx) in antipsychotic-naive first episode psychosis patients. Transl Psychiatry. 2024 Apr 10;14(1):183. doi: 10.1038/s41398-024-02854-7.
- 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.
- Derived from this study: PubMed 30852126Kraguljac NV, Anthony T, Skidmore FM, Marstrander J, Morgan CJ, Reid MA, White DM, Jindal RD, Melas Skefos NH, Lahti AC. Micro- and Macrostructural White Matter Integrity in Never-Treated and Currently Unmedicated Patients With Schizophrenia and Effects of Short-Term Antipsychotic Treatment. Biol Psychiatry Cogn Neurosci Neuroimaging. 2019 May;4(5):462-471. doi: 10.1016/j.bpsc.2019.01.002. Epub 2019 Jan 23.
- Derived from this study: PubMed 30286325Sivaraman S, Kraguljac NV, White DM, Morgan CJ, Gonzales SS, Lahti AC. Neurometabolic abnormalities in the associative striatum in antipsychotic-naive first episode psychosis patients. Psychiatry Res Neuroimaging. 2018 Nov 30;281:101-106. doi: 10.1016/j.pscychresns.2018.06.003. Epub 2018 Jun 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 C. Lahti, MD principal investigator
University of Alabama at Birmingham, Department of Psychiatry
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 Schizophrenia and 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 2 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: finished, as of the sponsor's last update on 22 Jan 2019. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Comparison of indices of glutamate as measured by 1H-MRS in unmedicated first episode psychosis patients before and after antipsychotic treatment and with healthy controls. (time frame: Up to 5 years). 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 NCT02034253, which also lists 6 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 22 Jan 2019.