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

Schizophrenia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT01458379
• Other study ID #: R092670SCH4005
• Status: Not yet recruiting
• Phase: Phase 4
• First received: October 13, 2011
• Last updated: June 14, 2012
• Start date: August 2012
• Est. completion date: December 2015

Study information

• Verified date: June 2012
• Source: University of California, Los Angeles
• Contact: George Bartzokis, M.D.
• Phone: 310-206-3207
• Email: gbar[@]ucla.edu
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: December 2015
• Est. primary completion date: October 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Schizophrenia

Intervention

Drug:
• Paliperidone Palmitate
Long acting injectable
• Risperidone
Oral

Locations

Country	Name	City	State
United States	UCLA Semel Institute for Neuroscience and Human Behavior	Los Angeles	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, Los Angeles	Ortho-McNeil Janssen Scientific Affairs, LLC

Country where clinical trial is conducted

United States, 

References & Publications (1)

Bartzokis G, Lu PH, Amar CP, Raven EP, Detore NR, Altshuler LL, Mintz J, Ventura J, Casaus LR, Luo JS, Subotnik KL, Nuechterlein KH. Long acting injection versus oral risperidone in first-episode schizophrenia: differential impact on white matter myelination trajectory. Schizophr Res. 2011 Oct;132(1):35-41. doi: 10.1016/j.schres.2011.06.029. Epub 2011 Jul 20. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Intracortical myelin	Change in frontal lobe intracortical myelin The total frontal lobe intracortical myelin will be the primary outcome measure.	12 months	No
Secondary	Cognition	Cognitive functioning based on CogState Battery The Complex Reaction Time measures of the CogState Battery will be secondary measures of cognitive outcome.	12 months	No
Secondary	Biomarker	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.	12 months	No