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Glutamate, Brain Connectivity and Duration of Untreated Psychosis (DUP)

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ClinicalTrials.gov Identifier: NCT02034253
Recruitment Status : Completed
First Posted : January 13, 2014
Last Update Posted : January 22, 2019
Sponsor:
Information provided by (Responsible Party):
Dr. Adrianne C Lahti, University of Alabama at Birmingham

Tracking Information
First Submitted Date January 8, 2014
First Posted Date January 13, 2014
Last Update Posted Date January 22, 2019
Actual Study Start Date January 2014
Actual Primary Completion Date November 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: January 9, 2014)
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 ]
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: January 9, 2014)
  • 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 ]
    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.
  • 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 ]
    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.
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Glutamate, Brain Connectivity and Duration of Untreated Psychosis
Official Title Glutamate, Brain Connectivity and Duration of Untreated Psychosis
Brief 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 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.

Detailed Description Not Provided
Study Type Observational
Study Design Observational Model: Case-Control
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Genes related to glutamate, n-acetyl-aspartate, dopamine, schizophrenia, and treatment response to antipsychotic medication will be collected.
Sampling Method Non-Probability Sample
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.

Condition
  • Schizophrenia
  • Psychosis
  • Schizoaffective Disorder
Intervention Drug: Risperidone
Patients with psychosis will be provided a 16 week regimen of the antipsychotic drug Risperidone in accordance with standard care.
Other Name: Risperdal
Study Groups/Cohorts
  • first episode psychosis
    Unmedicated first episode psychosis patients that wish to enroll in a 16 week treatment regimen with the drug Risperidone.
    Intervention: 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.
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: January 9, 2014)
134
Original Estimated Enrollment Same as current
Actual Study Completion Date November 2018
Actual Primary Completion Date November 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • Persons with first episode psychosis
  • Healthy controls will be matched to first episode psychosis participants on a one to one basis

Exclusion Criteria:

  • 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
Sex/Gender
Sexes Eligible for Study: All
Ages 17 Years to 35 Years   (Child, Adult)
Accepts Healthy Volunteers Yes
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT02034253
Other Study ID Numbers 1R01MH102951( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Dr. Adrianne C Lahti, University of Alabama at Birmingham
Study Sponsor University of Alabama at Birmingham
Collaborators Not Provided
Investigators
Principal Investigator: Adrienne C. Lahti, MD University of Alabama at Birmingham, Department of Psychiatry
PRS Account University of Alabama at Birmingham
Verification Date January 2019