- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03323437
Biomarkers of Conversion Risk and Treatment Response in Early-Stage Schizophrenia
Study Overview
Status
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Contact
- Name: Lawrence Kegeles, MD, Ph.D.
- Phone Number: 646-774-5560
- Email: lsk5@columbia.edu
Study Contact Backup
- Name: Ragy Girgis, MD
- Phone Number: 646-774-5553
- Email: ragy.girgis@nyspi.columbia.edu
Study Locations
-
-
New York
-
New York, New York, United States, 10032
- New York State Psychiatric Institute & Columbia University
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Patient
Medication-free individuals during first-episode of psychosis who will receive 4 weeks of treatment with risperidone
|
Participants will meet with a study doctor physician once per week (about 3 times total) to monitor progress and side-effects of risperidone, which includes taking 4 assessments each time.
After 4 weeks of taking Risperidone, participant will be assessed and scanned with the MRI/MRS scanner again.
|
No Intervention: Control
Healthy, psychosis-free controls who will not receive risperidone
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in biomarkers of treatment response: Dorsal Caudate (DCA) GABA levels
Time Frame: Baseline and 4 weeks of treatment
|
Dorsal Caudate (DCA) GABA levels will be ascertained at baseline and after 4 weeks of treatment using MRI scan with 1H MRS to assess treatment response.
|
Baseline and 4 weeks of treatment
|
Change in biomarkers of treatment response: Dorsal Caudate (DCA) Glutamate
Time Frame: Baseline and 4th week of treatment
|
Dorsal Caudate (DCA) Glutamate levels will be ascertained at baseline and after 4 weeks of treatment using MRI scan with 1H MRS to assess treatment response.
|
Baseline and 4th week of treatment
|
Change in biomarkers reflecting treatment response: Medial Prefrontal Cortex (MPFC) GABA
Time Frame: Baseline and 4th week of treatment
|
Medial Prefrontal Cortex (MPFC) GABA levels will be ascertained at baseline and after 4 weeks of treatment using MRI scan with 1H MRS to assess treatment response.
|
Baseline and 4th week of treatment
|
Change in biomarkers reflecting treatment response: Medial Prefrontal Cortex (MPFC) Glutamate
Time Frame: Baseline and 4th week of treatment
|
Medial Prefrontal Cortex (MPFC) Glutamate levels will be ascertained at baseline and after 4 weeks of treatment using MRI scan with 1H MRS to assess treatment response.
|
Baseline and 4th week of treatment
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes in neurocognitive performance: MATRICS Consensus Cognitive Battery (MCCB)
Time Frame: Baseline and 4th week of of treatment
|
Memory, attention, reasoning, emotional intelligence, and verbal ability will be assessed using the MCCB before and after 4 weeks of treatment.
|
Baseline and 4th week of of treatment
|
Changes in everyday functioning: University of California San Diego (UCSD) Performance-based Skills Assessment (UPSA)
Time Frame: Baseline and 4th week of treatment
|
Ability to function in a variety of everyday tasks from six domains (Financial Skills, Communication, Comprehension/Planning, Transportation, Household Management and Medication Management) will be assessed using the University of California San Diego Performance-based Skills Assessment (UPSA) before and after 4 weeks of treatment.
|
Baseline and 4th week of treatment
|
Changes in clinical symptomatology: Positive and Negative Syndrome Scale (PANSS)
Time Frame: Treatment week 1, treatment week 2, treatment week 3
|
Changes in Positive and Negative Symptoms will be assessed across the treatment period using the PANSS. Participants are rated on a scale of
to describe Positive, Negative and General symptomatology. Items from each subscale (Positive, Negative, and General) are summed for their respective scales, with lower numbers indicating less severe or absent symptomatology, and higher scores indicating more severe symptoms. A total sum of all subscales is also computed to reflect overall symptom severity. Positive Subscale: 7 items, minimum score = 7, maximum score = 49 Negative Subscale: 7 items, minimum score = 7, maximum score = 49 General Subscale: '16 items, minimum score = 16, maximum score = 112 Total Score: 30 items, minimum score = 30, maximum score = 210. |
Treatment week 1, treatment week 2, treatment week 3
|
Changes in motor symptomatology: Abnormal Involuntary Movement Scale (AIMS)
Time Frame: Treatment week 1, treatment week 2, treatment week 3
|
Changes in motor symptomatology associated with tardive dyskinesia (TD) assessed using the Abnormal Involuntary Movement Scale (AIMS). The measure consists of 14 items with scale 0 None
Item 8 = rating of overall symptom severity based on observation, using the same scale as above. Item 9 = rating of the incapacity of the subject due to abnormal movements, using the same scale as above. Item 10 = rating of the level of awareness and distress in the participant over the abnormal movements, with 0 =No Awareness
Item 14 = yes/no if symptoms disappear or persist during sleep. |
Treatment week 1, treatment week 2, treatment week 3
|
Changes in clinical severity: Clinical Global Impression Scale
Time Frame: treatment week 1, treatment week 2, treatment week 3
|
Changes in clinical severity over the course of treatment will be monitored using the The Clinical Global Impression Scale (CGI) consists of two items.- Severity scale (CGI-S). Severity - The first item assesses the patient's current level of mental health symptomatology compared to the clinician's experience with other patients with the same diagnosis. The scale ranges from
Improvement - The second item assesses how much the patient's symptomatology has changed since the last clinical visit.
|
treatment week 1, treatment week 2, treatment week 3
|
Changes in global functioning: Global Assessment of Functioning (GAF)
Time Frame: Treatment week 1, treatment week 2, treatment week 3
|
Changes in global functioning over the course of treatment will be assessed using the Global Assessment of Functioning (GAF). Participants are rated 1-100 on their level of functioning, according to clinical observation: 91 - 100 No symptoms. 81 - 90 Absent or minimal symptoms 71 - 80 If symptoms are present, they expected reactions to stressors 61 - 70 Some mild symptoms 51 - 60 Moderate symptoms 41 - 50 Serious symptoms 31 - 40 Impairment in reality testing or communication or major impairment in several areas 21-30 Behavior influenced by delusions or hallucinations or serious impairment in communication/judgment/inability to function in almost all areas 11-20 Some danger of hurting self or others or occasionally fails to maintain minimal personal hygiene or gross impairment in communication 1-10 Persistent violence risk or lack of self-care 0 No info |
Treatment week 1, treatment week 2, treatment week 3
|
Recreational Substances Used by Patients as Recorded by the Substance Use Questionnaire
Time Frame: This measure is administered on Day 1 of the study.
|
This measure is a self-reported questionnaire which assesses for any use of the following substances within the past month prior to the initial research visit Tobacco (if the respondent indicates that they have used tobacco in the past month, they are additionally asked, "On average, how many cigarettes per day have you smoked in the past 7 days?"
Alcohol, Cocaine, Marijuana, Opiates, Amphetamines, PCP Other Drugs of Abuse (if the respondent indicates they have used other drugs of abuse within the past month of the initial research visit, they are given the opportunity to "specify" which other drugs of abuse they used
|
This measure is administered on Day 1 of the study.
|
Participants' Verbal I.Q as Assessed by the WTAR to Determine Clinical Eligibility
Time Frame: This measure is completed on Day 1 of the study.
|
This measure assesses a participant's verbal ability to determine whether they are cognitively able to complete the measures involved in the study.
The participant will read from a list of 50 English words and the rater will record whether the pronunciation was correct on a score card for each word spoken.
A standard score below the 70th percentile on this measure is indicative of an intellectual disability which would exclude a participant from being clinically and cognitively eligible to complete this study.
|
This measure is completed on Day 1 of the study.
|
Participants' Self-Reported Handedness as Recorded by the Edinburgh Handedness Scale
Time Frame: This measure is completed on Day 1 of the study.
|
This measure assesses a participant's preference regarding which hand they would use to complete a specific task.
They have the option to indicate whether they would use they would always or most of the time use their left, right, or both left and right hands to complete each task.
This measure assesses handedness based on the amount of responses which indicate the participant is either left handed, right handed, or ambidextrous.
|
This measure is completed on Day 1 of the study.
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Dikoma C. Shungu, Ph.D., Weill Medical College of Cornell University
Publications and helpful links
General Publications
- Olney JW, Farber NB. Glutamate receptor dysfunction and schizophrenia. Arch Gen Psychiatry. 1995 Dec;52(12):998-1007. doi: 10.1001/archpsyc.1995.03950240016004.
- Perkins DO, Gu H, Boteva K, Lieberman JA. Relationship between duration of untreated psychosis and outcome in first-episode schizophrenia: a critical review and meta-analysis. Am J Psychiatry. 2005 Oct;162(10):1785-804. doi: 10.1176/appi.ajp.162.10.1785.
- Davis KL, Kahn RS, Ko G, Davidson M. Dopamine in schizophrenia: a review and reconceptualization. Am J Psychiatry. 1991 Nov;148(11):1474-86. doi: 10.1176/ajp.148.11.1474.
- Laruelle M, Abi-Dargham A. Dopamine as the wind of the psychotic fire: new evidence from brain imaging studies. J Psychopharmacol. 1999 Dec;13(4):358-71. doi: 10.1177/026988119901300405.
- Abi-Dargham A, Gil R, Krystal J, Baldwin RM, Seibyl JP, Bowers M, van Dyck CH, Charney DS, Innis RB, Laruelle M. Increased striatal dopamine transmission in schizophrenia: confirmation in a second cohort. Am J Psychiatry. 1998 Jun;155(6):761-7. doi: 10.1176/ajp.155.6.761.
- Laruelle M, Abi-Dargham A, van Dyck CH, Gil R, D'Souza CD, Erdos J, McCance E, Rosenblatt W, Fingado C, Zoghbi SS, Baldwin RM, Seibyl JP, Krystal JH, Charney DS, Innis RB. Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects. Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):9235-40. doi: 10.1073/pnas.93.17.9235.
- Fusar-Poli P, Borgwardt S, Bechdolf A, Addington J, Riecher-Rossler A, Schultze-Lutter F, Keshavan M, Wood S, Ruhrmann S, Seidman LJ, Valmaggia L, Cannon T, Velthorst E, De Haan L, Cornblatt B, Bonoldi I, Birchwood M, McGlashan T, Carpenter W, McGorry P, Klosterkotter J, McGuire P, Yung A. The psychosis high-risk state: a comprehensive state-of-the-art review. JAMA Psychiatry. 2013 Jan;70(1):107-20. doi: 10.1001/jamapsychiatry.2013.269.
- Coyle JT. The glutamatergic dysfunction hypothesis for schizophrenia. Harv Rev Psychiatry. 1996 Jan-Feb;3(5):241-53. doi: 10.3109/10673229609017192.
- Javitt DC, Zukin SR. Recent advances in the phencyclidine model of schizophrenia. Am J Psychiatry. 1991 Oct;148(10):1301-8. doi: 10.1176/ajp.148.10.1301.
- Krystal JH, Karper LP, Seibyl JP, Freeman GK, Delaney R, Bremner JD, Heninger GR, Bowers MB Jr, Charney DS. Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Arch Gen Psychiatry. 1994 Mar;51(3):199-214. doi: 10.1001/archpsyc.1994.03950030035004.
- Carlsson A, Waters N, Holm-Waters S, Tedroff J, Nilsson M, Carlsson ML. Interactions between monoamines, glutamate, and GABA in schizophrenia: new evidence. Annu Rev Pharmacol Toxicol. 2001;41:237-60. doi: 10.1146/annurev.pharmtox.41.1.237.
- CARLSSON A, LINDQVIST M. EFFECT OF CHLORPROMAZINE OR HALOPERIDOL ON FORMATION OF 3METHOXYTYRAMINE AND NORMETANEPHRINE IN MOUSE BRAIN. Acta Pharmacol Toxicol (Copenh). 1963;20:140-4. doi: 10.1111/j.1600-0773.1963.tb01730.x. No abstract available.
- Farooq S, Large M, Nielssen O, Waheed W. The relationship between the duration of untreated psychosis and outcome in low-and-middle income countries: a systematic review and meta analysis. Schizophr Res. 2009 Apr;109(1-3):15-23. doi: 10.1016/j.schres.2009.01.008. Epub 2009 Feb 23.
- Fusar-Poli P, Bonoldi I, Yung AR, Borgwardt S, Kempton MJ, Valmaggia L, Barale F, Caverzasi E, McGuire P. Predicting psychosis: meta-analysis of transition outcomes in individuals at high clinical risk. Arch Gen Psychiatry. 2012 Mar;69(3):220-9. doi: 10.1001/archgenpsychiatry.2011.1472.
- Lodge DJ, Grace AA. Aberrant hippocampal activity underlies the dopamine dysregulation in an animal model of schizophrenia. J Neurosci. 2007 Oct 17;27(42):11424-30. doi: 10.1523/JNEUROSCI.2847-07.2007.
- Moghaddam B, Adams B, Verma A, Daly D. Activation of glutamatergic neurotransmission by ketamine: a novel step in the pathway from NMDA receptor blockade to dopaminergic and cognitive disruptions associated with the prefrontal cortex. J Neurosci. 1997 Apr 15;17(8):2921-7. doi: 10.1523/JNEUROSCI.17-08-02921.1997.
- Olsen KA, Rosenbaum B. Prospective investigations of the prodromal state of schizophrenia: review of studies. Acta Psychiatr Scand. 2006 Apr;113(4):247-72. doi: 10.1111/j.1600-0447.2005.00697.x.
- Snyder SH. The dopamine hypothesis of schizophrenia: focus on the dopamine receptor. Am J Psychiatry. 1976 Feb;133(2):197-202. doi: 10.1176/ajp.133.2.197.
- Tamminga CA. Schizophrenia and glutamatergic transmission. Crit Rev Neurobiol. 1998;12(1-2):21-36. doi: 10.1615/critrevneurobiol.v12.i1-2.20.
- Tamminga CA, Holcomb HH, Gao XM, Lahti AC. Glutamate pharmacology and the treatment of schizophrenia: current status and future directions. Int Clin Psychopharmacol. 1995 Sep;10 Suppl 3:29-37.
- Yung AR, Yuen HP, Berger G, Francey S, Hung TC, Nelson B, Phillips L, McGorry P. Declining transition rate in ultra high risk (prodromal) services: dilution or reduction of risk? Schizophr Bull. 2007 May;33(3):673-81. doi: 10.1093/schbul/sbm015. Epub 2007 Apr 2.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Schizophrenia
- Psychotic Disorders
- Schizophrenia Spectrum and Other Psychotic Disorders
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Antipsychotic Agents
- Tranquilizing Agents
- Psychotropic Drugs
- Serotonin Agents
- Dopamine Agents
- Serotonin Antagonists
- Dopamine Antagonists
- Risperidone
Other Study ID Numbers
- 1702018001
- R01MH110270 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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