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Trajectories of Treatment Response as Window Into the Heterogeneity of Psychosis: a Longitudinal Multimodal Imaging Study

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ClinicalTrials.gov Identifier: NCT03442101
Recruitment Status : Recruiting
First Posted : February 22, 2018
Last Update Posted : April 22, 2019
Sponsor:
Information provided by (Responsible Party):
Dr. Adrianne C Lahti, University of Alabama at Birmingham

Tracking Information
First Submitted Date February 9, 2018
First Posted Date February 22, 2018
Last Update Posted Date April 22, 2019
Actual Study Start Date April 1, 2018
Estimated Primary Completion Date September 30, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: February 15, 2018)
  • 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.
Original Primary Outcome Measures Same as current
Change History Complete list of historical versions of study NCT03442101 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures
 (submitted: February 15, 2018)
  • Changes in measures of brain structure [ Time Frame: 32 weeks ]
    Changes in measures of brain structure over time that are associated with treatment response to antipsychotic medication.
  • Changes in measures of brain function [ Time Frame: 32 weeks ]
    Changes in measures of brain function over time that are associated with treatment response to antipsychotic medication.
  • Changes in measures of brain biochemistry [ Time Frame: 32 weeks ]
    Changes in measures of brain biochemistry over time that are associated with treatment response to antipsychotic medication.
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures
 (submitted: February 15, 2018)
  • Trajectory of treatment response [ Time Frame: 32 weeks ]
    Identification of clusters of participants following similar trajectories of treatment response over time, through measures of brain structure.
  • Trajectory of treatment response [ Time Frame: 32 weeks ]
    Identification of clusters of participants following similar trajectories of treatment response over time, through measures of brain function.
  • Trajectory of treatment response [ Time Frame: 32 weeks ]
    Identification of clusters of participants following similar trajectories of treatment response over time, through measures of brain biochemistry.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title Trajectories of Treatment Response as Window Into the Heterogeneity of Psychosis: a Longitudinal Multimodal Imaging 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
Brief 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.
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 Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples Without DNA
Description:
Antipsychotic drug plasma levels
Sampling Method Non-Probability Sample
Study Population First episode psychosis subjects
Condition Psychosis
Intervention Drug: Patients with psychosis will be treated with known antipsychotic medication
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.
Other Name: Brain imaging scans will be obtained 4 times during the study
Study Groups/Cohorts Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: February 15, 2018)
156
Original Estimated Enrollment Same as current
Estimated Study Completion Date March 31, 2023
Estimated Primary Completion Date September 30, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • A diagnosis of first episode psychosis
  • Never been treated with an antipsychotic medication
  • Between the age of 17 and 35

Exclusion Criteria:

  • 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
Sex/Gender
Sexes Eligible for Study: All
Ages 17 Years to 35 Years   (Child, Adult)
Accepts Healthy Volunteers Not Provided
Contacts
Contact: Kristen Edwards 205 996 7171 Ksenetto@uabmc.edu
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT03442101
Other Study ID Numbers R01NIMH113800
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
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 Not Provided
PRS Account University of Alabama at Birmingham
Verification Date April 2019