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Brain Myelination Effects of Paliperidone Palmitate Versus Oral Risperidone in First Episode Schizophrenia

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified June 2012 by University of California, Los Angeles
Sponsor:
Collaborator:
Ortho-McNeil Janssen Scientific Affairs, LLC
Information provided by (Responsible Party):
George Bartzokis, University of California, Los Angeles
ClinicalTrials.gov Identifier:
NCT01458379
First received: October 13, 2011
Last updated: June 14, 2012
Last verified: June 2012
  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

Resource links provided by NLM:


Further study details as provided by University of California, Los Angeles:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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:

    1. total frontal lobe myelinated white matter volume determined on inversion recovery images,
    2. 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,
    3. 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
Criteria

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
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: NCT01458379

Contacts
Contact: George Bartzokis, M.D. 310-206-3207 gbar@ucla.edu

Locations
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.         
Sponsors and Collaborators
University of California, Los Angeles
Ortho-McNeil Janssen Scientific Affairs, LLC
  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
Mental Disorders
Schizophrenia and Disorders with Psychotic Features
9-hydroxy-risperidone
Risperidone
Antipsychotic Agents
Central Nervous System Agents
Central Nervous System Depressants
Dopamine Agents
Dopamine Antagonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents
Serotonin Antagonists
Therapeutic Uses
Tranquilizing Agents

ClinicalTrials.gov processed this record on November 25, 2014