Dopamine D2 and D3 Receptor Occupancy and Clinical Response in Older Patients With Schizophrenia

NCT00825045 | Unknown

• 1 other identifier: 270/2008
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

This study will provide information regarding dopamine D2/D3 occupancy related with clinical/adverse effects in older people with schizophrenia and schizoaffective disorder. The results of this study will also show an appropriate dose range in order to evade undesirable adverse effects while deriving therapeutic effects, which will directly serve to guide physicians in clinical practice. Furthermore, the findings of this study will elucidate mechanisms underlying older people's increased sensitivity to antipsychotic drugs. In addition, the contribution of D2 and D3 in mediating antipsychotic response will be contrasted, using 2 radiotracers, which has never been tested in an older population. The hypotheses are as follows: First, clinical response (i.e., a ≥ 20% decrease in the Brief Psychiatric Rating Scale total score) will be achieved in older patients with occupancy that is lower than the threshold of 60% in historical young controls. Second, prolactin elevation and EPS will be detected in older patients with occupancies that are lower than the thresholds of 72 and 78% reported in historical young controls. Third, dopamine D2 receptor occupancy will be inversely correlated with subjective well-beings. Fourth, the binding potential and receptor occupancy will be at least 20% lower with \[11C\]-(+)-PHNO than with \[11C\]-raclopride in the caudate/putamen. Fifth, the binding of \[11C\]-(+)-PHNO in the globus pallidus will be higher than that of \[11C\]-raclopride.

Conditions

Schizophrenia; Schizoaffective Disorder; Schizophreniform Disorder

Keywords

dopamine; D2; D3; caudate; putamen; globus pallidus; antipsychotic; risperidone; geriatric; Brief Psychiatric Rating Scale; PET; radiotracer; [11C]-(+)-PHNO; [11C]-raclopride

Outcome Measures

Primary Outcomes (1)

• The occupancy of risperidone at the D2 and D3 receptor, using [11C]-raclopride and [11C]-(+)-PHNO, respectively.

  Within 3 months of enrollment

Secondary Outcomes (1)

• Plasma levels of risperidone and 9-hydroxyrisperidone

  Within 3 months of enrollment

Study Arms (1)

Treatment with risperidone

EXPERIMENTAL

Gradual titration of risperidone according to clinical response

Drug: risperidone

Interventions

risperidone DRUG

Following the baseline clinical and cognitive assessments, risperidone will be initiated at 0.5-1.0 mg/day and subsequently increased by 0.25 - 1.0 mg on a weekly basis with the target of clinical stabilization (i.e. 20 or more % reduction in the total BPRS score) until a maximum dose of 4.0 mg/day is reached. To achieve this, a weekly assessment with BPRS will be performed. Physicians-of-record will be closely liaised with investigators. Dosage modification will be performed following this dosing schedule, however, this can be changed by treating physicians to meet clinical necessity. For example, in case psychotic symptoms are not controlled by this dosing schedule, facilitated dose increment will be allowed.

Treatment with risperidone

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age of 50 and older at time of scanning
• Inpatients or outpatients
• DSM-IV/SCID diagnosis of schizophrenia, schizoaffective disorder, or schizophreniform disorder

You may not qualify if:

• Known history of intolerance or inefficacy to risperidone
• Participation in this study would result in exceeding the annual radiation dose limits (20 mSv) for human subjects participating in research studies.
• Substance abuse or dependence (within past six months)
• Positive urine drug screen
• Positive serum pregnancy test at screening or positive urine pregnancy test before PET scan
• Metal implants or a pace-maker that would preclude the MRI scan
• History of head trauma resulting in loss of consciousness \>30 minutes that required medical attention
• Unstable physical illness or significant neurological disorder including a seizure disorder
• Inappropriate size of head, neck, and body to be able to fit the PET and MRI scans

Sponsors & Collaborators

• Centre for Addiction and Mental Health: lead

Study Sites (1)

Centre for Addiction and Mental Health

Toronto, Ontario, M5T 1R8, Canada

Location

Related Links

• Information about research at the Centre for Addiction and Mental Health

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Interventions

Risperidone

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Ariel Graff-Guerrero, MD, PhD

  Centre for Addiction and Mental Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: January 16, 2009
• First Posted: January 19, 2009
• Study Start: December 1, 2008
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2020
• Last Updated: February 7, 2020

Record last verified: 2020-02

Locations

CA (1)