Dopamine D2 and D3 Receptor Occupancy and Clinical Response in Older Patients With Schizophrenia
Information source: Centre for Addiction and Mental Health
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Schizophrenia; Schizoaffective Disorder; Schizophreniform Disorder
Intervention: risperidone (Drug)
Phase: N/A
Status: Recruiting
Sponsored by: Centre for Addiction and Mental Health Official(s) and/or principal investigator(s): David Mamo, MD, MSc, Principal Investigator, Affiliation: Centre for Addiction and Mental Health Ariel Graff-Guerrero, MD, PhD, Principal Investigator, Affiliation: Centre for Addiction and Mental Health
Overall contact: Ariel Graff-Guerrero, MD, PhD, Phone: 416-535-8501, Ext: 34834, Email: ariel.graff@camh.ca
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.
Clinical Details
Official title: Dopamine D2 and D3 Receptor Occupancy and Clinical Response in Older Patients With Schizophrenia
Study design: Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: The occupancy of risperidone at the D2 and D3 receptor, using [11C]-raclopride and [11C]-(+)-PHNO, respectively.
Secondary outcome: Plasma levels of risperidone and 9-hydroxyrisperidone
Detailed description:
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.
Eligibility
Minimum age: 50 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
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
Locations and Contacts
Ariel Graff-Guerrero, MD, PhD, Phone: 416-535-8501, Ext: 34834, Email: ariel.graff@camh.ca
Centre for Addiction and Mental Health, Toronto, Ontario M5T 1R8, Canada; Recruiting Bruce Pollock, MD, PhD, Sub-Investigator Benoit Mulsant, MD, MSc, Sub-Investigator Shinichiro Nakajima, MD, PhD, Sub-Investigator
Additional Information
Information about research at the Centre for Addiction and Mental Health
Starting date: December 2008
Last updated: August 21, 2015
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