Trial record 7 of 4489 for:    Open Studies | "Psychotic Disorders"

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by University of Alabama at Birmingham
Sponsor:
Information provided by (Responsible Party):
Dr. Adrianne C Lahti, University of Alabama at Birmingham
ClinicalTrials.gov Identifier:
NCT02034253
First received: January 8, 2014
Last updated: January 9, 2014
Last verified: January 2014
  Purpose

The early stages of the schizophrenia illness are associated with significant decreases in social and intellectual abilities, with more modest declines seen with chronic disease. Multiple studies have identified a relationship between the longer 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 commonly prescribed antipsychotic. We will measure indices of (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 healthy controls will also be recruited as a comparison group - healthy controls will not be administered antipsychotic medication.

The investigator's previous neuroimaging 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 suggestive of glutamate/ glutamine cycle abnormalities have been identified. While antipsychotic medications appear to modulate glutamate, the disturbance in the correlation 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' subsequent 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 their 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.


Condition Intervention
Schizophrenia
Psychosis
First Episode Psychosis
Drug: Risperidone

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Glutamate, Brain Connectivity and Duration of Untreated Psychosis

Resource links provided by NLM:


Further study details as provided by University of Alabama at Birmingham:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 134
Study Start Date: January 2014
Estimated Study Completion Date: November 2018
Estimated Primary Completion Date: November 2018 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
first episode psychosis
Unmedicated first episode psychosis patients that wish to enroll in a 16 week treatment regimen with the drug risperdal.
Drug: Risperidone
Other Name: Risperdal
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.

  Eligibility

Ages Eligible for Study:   17 Years to 35 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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 male and female healthy 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 or aging effects rather than diagnosis, and because adults over 35 are more likely to be taking medications that could put them at greater risk.

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02034253

Contacts
Contact: David White, MPH, MPA 205-996-9813 dw2777@uab.edu
Contact: Ariel Kidwell, BS 205-996-9813 akidwell@uab.edu

Locations
United States, Alabama
Sparks Center Recruiting
Birmingham, Alabama, United States, 35294
Contact: David White, MPH, MPA    205-996-9813    dw2777@uab.edu   
Contact: Ariel Kidwell, BS    205-996-9813    akidwell@uab.edu   
Principal Investigator: Adrienne C Lahti, MD         
Sponsors and Collaborators
University of Alabama at Birmingham
Investigators
Principal Investigator: Adrienne C. Lahti, MD University of Alabama at Birmingham, Department of Psychiatry
  More Information

No publications provided

Responsible Party: Dr. Adrianne C Lahti, Professor and Division Director of Behavioral Neurobiology, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT02034253     History of Changes
Other Study ID Numbers: 1R01MH102951
Study First Received: January 8, 2014
Last Updated: January 9, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration
United States: National Institute of Mental Health

Keywords provided by University of Alabama at Birmingham:
duration of untreated psychosis
glutamate
functional connectivity
structural connectivity
schizophrenia
psychosis

Additional relevant MeSH terms:
Mental Disorders
Psychotic Disorders
Schizophrenia and Disorders with Psychotic Features
Schizophrenia
Risperidone
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
Dopamine Antagonists
Dopamine Agents

ClinicalTrials.gov processed this record on July 24, 2014