- ICH GCP
- 미국 임상 시험 레지스트리
- 임상시험 NCT00825045
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.
연구 개요
상세 설명
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.
연구 유형
등록 (예상)
단계
- 해당 없음
연락처 및 위치
연구 장소
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Ontario
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Toronto, Ontario, 캐나다, M5T 1R8
- Centre for Addiction and Mental Health
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
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
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 해당 없음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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실험적: Treatment with risperidone
Gradual titration of risperidone according to clinical response
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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.
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
기간 |
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The occupancy of risperidone at the D2 and D3 receptor, using [11C]-raclopride and [11C]-(+)-PHNO, respectively.
기간: Within 3 months of enrollment
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Within 3 months of enrollment
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2차 결과 측정
결과 측정 |
기간 |
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Plasma levels of risperidone and 9-hydroxyrisperidone
기간: Within 3 months of enrollment
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Within 3 months of enrollment
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공동 작업자 및 조사자
수사관
- 수석 연구원: Ariel Graff-Guerrero, MD, PhD, Centre for Addiction and Mental Health
간행물 및 유용한 링크
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
기본 완료 (예상)
연구 완료 (예상)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (추정)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
키워드
추가 관련 MeSH 약관
기타 연구 ID 번호
- 270/2008
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .
risperidone에 대한 임상 시험
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Otsuka Beijing Research InstituteZhejiang Otsuka Pharmaceutical Co., Ltd.완전한