Raloxifene Augmentation in Patients With a Schizophrenia Spectrum Disorder to Reduce Symptoms and Improve Cognition
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Iris Sommer
- 入组人数
- 110
- 试验地点
- 1
- 主要终点
- Change in symptom severity as measured with the Positive and Negative Symptom Scale (PANSS)
研究概览
简要总结
There is increasing clinical and molecular evidence for the role of hormones and specifically estrogen and its receptor in schizophrenia. A selective estrogen receptor modulator, raloxifene, stimulates estrogen-like activity in brain and can improve cognition in older adults. The present study will test the extent to which adjunctive raloxifene treatment improved cognition and reduced symptoms in young to middle-age men and women with schizophrenia.
110 patients with a schizophrenia spectrum disorder will be recruited in a multicenter twelve-week, randomized, double-blind, placebo-controlled, parallel trial of adjunctive 120mg raloxifene treatment in addition to their usual antipsychotic medications.
The investigators hypothesize that daily treatment with raloxifene 120 milligrams (mg) in addition to antipsychotic treatment improves cognition, reduces psychotic symptoms, increases social and personal functioning and reduces health care costs, as compared to placebo.
详细描述
Rationale:
Patients with a schizophrenia spectrum disorder experience substantial impairments in multiple domains of everyday life, including the ability to maintain social relationships, sustain employment, and live independently. These problems often persist, even after successful treatment of psychosis. Currently, no consistent evidence exists for the efficacy of interventions to reduce cognitive and negative symptoms, while in fact these are the factors that determine functioning to a great extent.
Premenopausal women with schizophrenia have less psychotic and negative symptoms, and better cognitive and social functioning, in comparison to men and older women. This has been related to protective effects of estrogens in the brain. Administering estrogens has positive effects on psychotic symptoms, but exerts long-term side effects, especially in men.
Raloxifene is a selective estrogen receptor modulator, with a beneficial side effect profile in women and in men. It has been shown to be effective in reducing symptoms in postmenopausal women with schizophrenia. Recently, positive results were found in premenopausal women and in men. It is important to replicate these results in an independent sample and to investigate the effects of raloxifene on functioning.
Hypotheses: Daily treatment with raloxifene 120 milligrams (mg) in addition to antipsychotic treatment improves cognition, reduces psychotic symptoms, increases social and personal functioning and reduces health care costs, as compared to placebo.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A DSM-IV-R diagnosis of: 295.x (schizophrenia, schizophreniform disorder, schizoaffective disorder, or psychotic disorder NOS)
- •Capable of understanding the purpose and details of the study in order to provide written informed consent;
- •On a stable dose of antipsychotic medication for at least two weeks;
- •For female patients:
- •Female patients who are sexually active must be willing and capable to use a non-estrogenic contraceptive (intrauterine device, cervical cap, condom or diaphragm) in case of sexual intercourse for the complete duration of the study;
- •Female patients with post coital uterine bleeding must have documented normal PAP smear and pelvic examination in the preceding two years.
排除标准
- •Pre-existing cardiovascular disease;
- •History of thrombo-embolic events;
- •History of breast cancer;
- •Familial tendency to form blood clots (such as familial factor V Leiden);
- •Use of vitamin K antagonists;
- •Use of cholestyramine or other anion exchange resins;
- •Hypertriglyceridemia (triglycerides > 3 times the upper limit of normal (ULN));
- •Liver function or enzyme disorders (serum bilirubin, alkaline phosphatase (AF), gamma-glutamyl transpeptidase (γ - GT), aspartate aminotransferase (ASAT) or alanine aminotransferase (ALAT) > 3 times the ULN as measured at baseline);
- •Severe kidney failure (eGFR <30 ml/min as measured at baseline);
- •Use of any form of estrogen, progestin or androgen as hormonal therapy, or antiandrogen including tibolone or use of phytoestrogen supplements as powder or tablet in the past three months.
- •For female patients:
- •Abnormality observed during physical breast examination;
- •Pregnancy or breast feeding;
研究组 & 干预措施
Raloxifene
Raloxifene 120 mg (2 tablets of 60mg) daily for 12 weeks.
干预措施: Raloxifene (Drug)
Placebo
Placebo 2 tablets daily for 12 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Change in symptom severity as measured with the Positive and Negative Symptom Scale (PANSS)
时间窗: Baseline, at 6 weeks of treatment, at 12 weeks of treatment (end of treatment) and 6 months after end of treatment (follow-up)
Effect of the study therapies on symptom severity.
Change in cognitive functioning as measured with the Brief Assessment of Cognition in Schizophrenia
时间窗: Baseline, at 12 weeks (end of treatment) and 6 months after end of treatment (follow-up)
Effect of the study therapies on cognitive functioning
次要结局
- Participant's Quality of Life as measured with the EQ-5D-5L(Baseline, at 12 weeks (end of treatment) and 6 months after end of treatment (follow-up))
- Use of non-health recourses as measured with the iMTA-PCQ(Baseline, at 12 weeks (end of treatment) and 6 months after end of treatment (follow-up))
- Thought disorder severity as measured with the Thought And Language Disorder scale (TALD)(Baseline, at 6 weeks, at 12 weeks (end of treatment) and 6 months after end of treatment (follow-up))
- Language production assessment by analyzing speech samples(Baseline and at 12 weeks of treatment (end of treatment))
- Symptom severity as measured with the Brief Negative Symptom Scale (BNSS)(Baseline, at 6 weeks, at 12 weeks (end of treatment) and 6 months after end of treatment (follow-up))
- Personal and social performance measured with the Personal and Social Performance scale (PSP)(Baseline, at 6 weeks, at 12 weeks (end of treatment) and 6 months after end of treatment (follow-up))
- Comorbid depression as measured with Beck's Depression Inventory (BDI).(Baseline, at 6 weeks, at 12 weeks (end of treatment) and 6 months after end of treatment (follow-up))
- Use of health-recourses as measured with the iMTA-MCQ(Baseline, at 12 weeks (end of treatment) and 6 months follow-up)