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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Centre for Addiction and Mental Health
Sponsor:
Information provided by (Responsible Party):
Ariel Graff, Centre for Addiction and Mental Health
ClinicalTrials.gov Identifier:
NCT00825045
First received: January 16, 2009
Last updated: March 19, 2014
Last verified: March 2014

January 16, 2009
March 19, 2014
December 2008
December 2015   (final data collection date for primary outcome measure)
The occupancy of risperidone at the D2 and D3 receptor, using [11C]-raclopride and [11C]-(+)-PHNO, respectively. [ Time Frame: Within 3 months of enrollment ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00825045 on ClinicalTrials.gov Archive Site
Plasma levels of risperidone and 9-hydroxyrisperidone [ Time Frame: Within 3 months of enrollment ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Dopamine D2 and D3 Receptor Occupancy and Clinical Response in Older Patients With Schizophrenia
Dopamine D2 and D3 Receptor Occupancy and Clinical Response in Older Patients With Schizophrenia

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.

Positron Emission Tomography (PET) studies have demonstrated that a therapeutic window of dopamine D2/3 receptor occupancy (60-80%) is associated with clinical response in younger patients with schizophrenia. This observation has been used to predict the therapeutic dose range and contributed to current recommended antipsychotic doses. To date, there is no published report to examine D2/3 receptor occupancy associated with clinical response in older individuals with primary psychotic disorders. This has has impeded the implementation of treatment guidelines.

The investigators therefore propose a prospective study to assess dopamine D2 and D3 receptor occupancy following acute antipsychotic treatment in patients aged 50 and older with schizophrenia who do not currently receive antipsychotic treatment, using both [11C]-(+)-PHNO and [11C]-raclopride PET scans. Dopamine D2/3 receptor occupancy of risperidone that are associated with clinical effects will be measured, using PET, in older patients with schizophrenia. The investigators will also try to contrast the contribution of D2 and D3 in mediating antipsychotic response, using 2 radiotracers.

Our primary goal is to relate changes in clinical outcome, including subjective and objective clinical ratings, to dopamine D2 and D3 receptor occupancy in older patients with schizophrenia, and compare these results with the data for younger patients in the literature.

Interventional
Not Provided
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Schizophrenia
  • Schizoaffective Disorder
  • Schizophreniform Disorder
Drug: risperidone
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.
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
10
Not Provided
December 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Age of 50 and older at time of scanning
  • Inpatients or outpatients
  • DSM-IV/SCID diagnosis of schizophrenia, schizoaffective disorder, or schizophreniform disorder
  • Having NOT been treated with oral antipsychotic treatment for at least 2 weeks or long-acting antipsychotics for at least 6 months (Please note that patients will not be withdrawn from antipsychotic medications for the purpose of meeting inclusion criteria for this study).

Exclusion Criteria:

  • 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
Both
50 Years and older
No
Contact: Ariel Graff-Guerrero, MD, PhD 416-535-8501 ext 34834 ariel.graff@camh.ca
Canada
 
NCT00825045
270/2008
No
Ariel Graff, Centre for Addiction and Mental Health
Centre for Addiction and Mental Health
Not Provided
Principal Investigator: David Mamo, MD, MSc Centre for Addiction and Mental Health
Principal Investigator: Ariel Graff-Guerrero, MD, PhD Centre for Addiction and Mental Health
Centre for Addiction and Mental Health
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP