Phase 4
N=26
Biomarkers of Conversion Risk and Treatment Response in Early-Stage Schizophrenia
Schizophrenia Spectrum and Other Psychotic Disorders
Bottom Line
View on ClinicalTrials.gov: NCT03323437 ↗Enrolled (actual)
26
Serious AEs
0.0%
Results posted
May 2024
Primary outcome: Primary: Change in Biomarkers of Treatment Response: Dorsal Caudate (DCA) Gamma Amino Butyric Acid (GABA) Levels — -0.65; .0037 institutional units — p=<0.01
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 4
- Interventions
- Risperidone (Drug)
- Age
- Adult · 18+ yrs
- Sex
- All
- Sponsor
- Weill Medical College of Cornell University
- Primary completion
- May 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change in Biomarkers of Treatment Response: Dorsal Caudate (DCA) Gamma Amino Butyric Acid (GABA) Levels |
-0.65; .0037 | <0.01 sig |
| PRIMARY Change in Biomarkers of Treatment Response: Dorsal Caudate (DCA) Glx (Glutamate+Glutamine) |
-.28; .00221 | .68 |
| PRIMARY Change in Biomarkers Reflecting Treatment Response: Medial Prefrontal Cortex (MPFC) Gamma Amino Butyric Acid (GABA) |
.85; .00247 | .03 sig |
| PRIMARY Change in Biomarkers Reflecting Treatment Response: Medial Prefrontal Cortex (MPFC) Glx (Glutamate+Glutamine) |
0.19; .00191 | .01 sig |
| SECONDARY Changes in Neurocognitive Performance: MATRICS Consensus Cognitive Battery (MCCB) |
0.222; 42.9 | .59 |
| SECONDARY WAMI (Wealth Asset and Income) |
.901; .982 | .45 |
| SECONDARY Changes in Clinical Symptomatology: Positive and Negative Syndrome Scale (PANSS) |
-0.09; 31.89 | .32 |
| SECONDARY Changes in Motor Symptomatology: Abnormal Involuntary Movement Scale (AIMS) |
-.077 | .60 |
| SECONDARY Changes in Clinical Severity: Clinical Global Impression Scale |
-0.054; 1 | .34 |
| SECONDARY Changes in Global Functioning: Global Assessment of Functioning (GAF) |
0.21; 86.4 | .35 |
| SECONDARY Recreational Substances Used by Patients as Recorded by the Substance Use Questionnaire |
6; 4 | .66 |
| SECONDARY Participants' Verbal I.Q (Intelligence Quotient) as Assessed by the WTAR (Wechsler Test of Adult Reading) to Determine Clinical Eligibility |
36.9; 43.9 | .04 sig |
| SECONDARY Participants' Self-Reported Handedness as Recorded by the Edinburgh Handedness Scale (Predominantly Right) |
11; 7 | 1 |
Summary
Schizophrenia (SZ) is a highly debilitating neuropsychiatric disorder of young adulthood onset and a leading cause of disability worldwide. While treatments delivered at early stages of the disorder may be effective at reducing psychosis or altering the course of the disease, there are currently no biomarkers capable of identifying subjects in early stages of SZ who are likely to respond to treatment and would be good candidates for available proactive, symptomatic or future disease-modifying treatments; or those who would not respond and can be spared unnecessary medication exposure. The lack of these vitally important biomarkers provides a compelling rationale for the present multidisciplinary research project, which aims to develop and validate highly promising noninvasive and objective proton magnetic resonance spectroscopy (1H MRS)-based biomarkers for monitoring treatment response in early stages of SZ. In support of the viability of this overall objective is a large body of data, reported by the applicants and others, that show (a) that levels of glutamate (Glu) and - aminobutyric acid (GABA) - respectively, the major excitatory and inhibitory amino acid neurotransmitter systems - are abnormally elevated in medication-naïve and unmedicated first episode and chronic SZ patients; (b) that the effect of treatment with antipsychotic medications in these populations may be to lower or normalize brain levels of both Glu and GABA. To investigate the potential of these in vivo brain Glu and GABA abnormalities to serve as biomarkers of treatment response in early-stage SZ, the applicants propose to use 1H MRS to measure Glu and GABA levels in the largest cohort of medication-free SZ subjects to date, at baseline and following 4 weeks of antipsychotic treatment.
Eligibility Criteria
Inclusion Criteria (Patients):
- Male or females between the ages of 18-35
- less than five years (<60 months) of active Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnosis of schizophrenia, schizophreniform, or schizoaffective disorder
- Capacity to provide informed consent
- No major medical or neurological illness
- Medication free (3 weeks without antipsychotic medications)
Exclusion Criteria (Patients):
- Current alcohol or drug abuse (<1 month) or substance dependence (<6 months) or substances used within one day of the imaging study.
- Pregnant or lactating women or women of child-bearing potential, who are either not surgically-sterile or, for outpatients, not using appropriate methods of birth control.
- Intelligence Quotient (IQ) <70
- Acute risk for suicide or violence
- Presence of pacemaker or any metallic objects in the body that would interfere with the MRS or cause MRI safety problems
- Claustrophobia
- Any organic brain disorder (including epilepsy, mental retardation, or a medical condition whose pathology or treatment would likely alter the presentation or treatment of SZ
- Individuals on anti-epileptic medications (e.g., valproate, carbamazepine) that may affect GABA or Glu
- Unstable medical or neurological condition
- DSM-V diagnosis of bipolar disorder I
- DSM-V diagnosis of major depression with psychotic features
- History of non-response to or non-tolerance of Risperidone
Inclusion Criteria (Healthy Controls)
- Male or females between the ages of 18-35
- less than five years (<60 months) of active DSM diagnosis of schizophrenia, schizophreniform, or schizoaffective disorder
- No major medical or neurological illness
Exclusion Criteria (Healthy Controls)
- Current alcohol or drug abuse (<1 month) or substance dependence (<6 months) or substances used within one day of the imaging study.
- Pregnant or lactating women or women of child-bearing potential, who are either not surgically-sterile or, for outpatients, not using appropriate methods of birth control.
- IQ<70
- Acute risk for suicide or violence
- Presence of pacemaker or any metallic objects in the body that would interfere with the MRS or cause MRI safety problems
- Claustrophobia
- History of psychotropic medication use such as antipsychotics or antidepressants
- Any first-degree family history of psychotic illness
- Personal history of any DSM Axis I disorder
- Individuals on anti-epileptic medications (e.g., valproate, carbamazepine) that may affect GABA or Glu
- Unstable medical or neurological condition
- Any organic brain disorder (including epilepsy, mental retardation, or a medical condition whose pathology or treatment would likely alter the presentation or treatment of SZ
Data sourced from ClinicalTrials.gov (NCT03323437). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.