Brain Myelination Effects of Paliperidone Palmitate Versus Oral Risperidone in First Episode Schizophrenia
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Purpose
This study will determine the effects on brain myelination and cognition of oral risperidone (Risperdal) versus long-acting injectable paliperidone palmitate (Invega Sustenna) in first-episode schizophrenia subjects. The hypothesis being tested is that continual inhibition of enzymes such as glycogen synthetase kinase 3 provided by injectable paliperidone palmitate will promote myelination to a greater extent than oral risperidone.
| Condition | Intervention | Phase |
|---|---|---|
|
Schizophrenia |
Drug: Paliperidone Palmitate Drug: Risperidone |
Phase 4 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Brain Myelination Effects of Paliperidone Palmitate vs. Oral Risperidone in First Episode Schizophrenia |
- Intracortical myelin [ Time Frame: 12 months ] [ Designated as safety issue: No ]Change in frontal lobe intracortical myelin The total frontal lobe intracortical myelin will be the primary outcome measure.
- Cognition [ Time Frame: 12 months ] [ Designated as safety issue: No ]Cognitive functioning based on CogState Battery The Complex Reaction Time measures of the CogState Battery will be secondary measures of cognitive outcome.
- Biomarker [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Change in other brain imaging biomarkers:
- total frontal lobe myelinated white matter volume determined on inversion recovery images,
- subcortical white matter integrity in orbitofrontal white matter and genu of corpus callosum assessed with radial diffusivity on diffusion tensor images and transvesre relaxation rate assessed with spin-echo images,
- whole brain white and gray matter volume changes assessed with vector based morphometry using 3D T1-weighted images
will be the imaging outcome measures.
| Estimated Enrollment: | 50 |
| Study Start Date: | August 2012 |
| Estimated Study Completion Date: | December 2015 |
| Estimated Primary Completion Date: | October 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Experimental: paliperidone palmitate (Invega Sustenna)
Participants will be provided paliperidone palmitate (Invega Sustenna), administered in injectible long-acting form, plus group skills training and case management
|
Drug: Paliperidone Palmitate
Long acting injectable
|
|
Active Comparator: Active Comparator: oral risperidone
Participants will be provided oral risperidone, plus group skills training and case management
|
Drug: Risperidone
Oral
|
Detailed Description:
Schizophrenia is a severely disabling brain disorder. People with schizophrenia often experience hallucinations, delusions, thought disorders, and movement disorders. Proper treatment of first-episode schizophrenia may increase the chances of controlling disease progression on a long-term basis. People experiencing their first episode of schizophrenia are more responsive to treatment than those with chronic schizophrenia, but are also more susceptible to adverse treatment side effects. Atypical antipsychotic medications have been shown to produce fewer extrapyramidal side effects than older "typical" antipsychotics. Oral risperidone is an atypical antipsychotic medication that is very commonly used to control the symptoms of schizophrenia. Adherence to prescribed oral medication continues to be a major clinical issue.
This study will determine the effectiveness of oral risperidone versus a long-acting injectable alternative, paliperidone palmitate, in improving brain myelination and cognitive function in people with first-episode schizophrenia. Impact on brain myelination and clinical symptoms will be examined to test the hypothesis that brain myelination changes underlie one of the mechanisms of action of antipsychotics. This study will assess biomarkers at baseline (pre randomization), 6 months, and end of "parent study" participation.
Participants in the "parent" open label study will be randomly assigned to receive either orally administered risperidone or long-acting paliperidone palmitate administered via injection. Participants assigned to oral risperidone will receive medication in doses that are determined to be optimal by the study psychiatrist. Participants assigned to long-acting risperidone will receive an injection of paliperidone palmitate once every 4 weeks. Dosages will be adjusted as necessary to achieve the optimal dosage. Following 2 to 3 months to achieve outpatient oral risperidone dosage stabilization, the randomized medication conditions will begin and participants will be monitored for 1 year. Parent study visits will occur once weekly throughout the study. They will include psychiatrist monitoring of medication response and side effects; group therapy meetings focused on everyday living skills; family education about schizophrenia; and individual meetings with a case manager for counseling and evaluations of schizophrenia symptoms, work recovery, and social functioning.
Eligibility| Ages Eligible for Study: | 18 Years to 45 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
Inclusion Criteria (identical to clinical trial "parent study"):
- A first episode of a psychotic illness is occurring or did occur within the last 2 years;
- A diagnosis by DSM-IV of schizophrenia, schizoaffective disorder, depressed type, or schizophreniform disorder; and
- Between 18 and 45 years of age.
Exclusion Criteria (identical to clinical trial "parent study"):
- Neurological disorder (e.g., epilepsy) or significant head injury;
- Significant alcohol or substance use disorder within the six months prior to the first episode and evidence that substance abuse triggered the psychotic episode or makes the schizophrenia diagnosis ambiguous;
- Mental retardation, i.e. premorbid IQ less than 70;
- Insufficient acculturation and fluency in the English language to avoid invalidating research measures of thought, language, and speech disorder or of verbal abilities;
- Residence likely to be outside of commuting distance of the UCLA Aftercare Research Program; or
- Patient has shown an inadequate response to an adequate previous trial of oral or long-acting injectable risperidone, paliperidone, or paliperidone palmitate.
Contacts and Locations| Contact: George Bartzokis, M.D. | 310-206-3207 | gbar@ucla.edu |
| United States, California | |
| UCLA Semel Institute for Neuroscience and Human Behavior | Not yet recruiting |
| Los Angeles, California, United States, 90095 | |
| Contact: George Bartzokis, M.D. 310-206-3207 gbar@ucla.edu | |
| Sub-Investigator: George Bartzokis, M.D. | |
More Information
Publications:
| Responsible Party: | George Bartzokis, Professor in Residence, University of California, Los Angeles |
| ClinicalTrials.gov Identifier: | NCT01458379 History of Changes |
| Other Study ID Numbers: | R092670SCH4005 |
| Study First Received: | October 13, 2011 |
| Last Updated: | June 14, 2012 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by University of California, Los Angeles:
|
Myelination Intracortical Subcortical MRI |
mode of delivery of antipsychotic medication schizophrenia first episode First Episode Schizophrenia |
Additional relevant MeSH terms:
|
Schizophrenia Schizophrenia and Disorders with Psychotic Features Mental Disorders Risperidone 9-hydroxy-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 May 21, 2013