Multisite Double-Blind Randomized Controlled Study of Estradiol Plus Antipsychotic Versus Placebo Plus Antipsychotic in the Treatment of Psychotic Symptoms in Women With Schizophrenia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 180
- 试验地点
- 1
- 主要终点
- Positive and Negative Syndrome Scale (PANSS)
研究概览
简要总结
OBJECTIVE:
To test the use of adjunctive estrogen in a 8 week, three-arm, double-blind, placebo-controlled study in the treatment of psychotic symptoms in women with schizophrenia.
HYPOTHESIS:
That women receiving adjunctive estrogen will demonstrate significantly greater improvements in the symptoms of schizophrenia than women receiving adjunctive placebo.
STUDY POPULATION:
180 women will be recruited over a three-year period across three sites. Participant will be of potential child-bearing age (Pre-menopausal and Post-menarche) with a current diagnosis of Schizophrenia, Schizophreniform Disorder, or Schizoaffective Disorder (not in manic phase)according to the Mini International Neuropsychiatric Interview (MINI).
STUDY MEDICATION:
Estradiol. One third of the participants (n=60) will be randomised to receive adjunctive 100mcg Estradiol; one third of the participants (n=60) will be randomised to receive adjunctive 200mcg Estradiol n=60; and, one third of the participants (n=60) will be randomised to receive adjunctive placebo n=60). All patches will be covered with identical adhesive contact to ensure the "blind" is maintained.
STUDY EVALUATIONS:
Data will be collected over a two-month period for each participant. Visits will be performed at baseline, and then at weekly or fortnightly intervals. A total of six visits will be completed for each participant. The following evaluations will be performed:
i) Inclusion/exclusion checklist. (Baseline visit only)
ii) Informed consent. (Baseline visit only)
iii)psychiatric evaluation to determine diagnosis. (Baseline visit only)
iv) General clinical evaluation including medical history, current conditions and a non-invasive physical examination, body weight, vital signs. (Baseline and endpoint visits)
v) Medication history. (Baseline and evaluation visits)
vi) Demographics. (Baseline visits only)
vii) The primary outcome measures will be the Positive and Negative Syndrome Scale (PANSS), which will be taken at weeks 1, 2, 4 and 8 of the trial. Cognitive testing will take place at baseline and 8 weeks. Side effects will be assessed at weeks 1, 2, 4, 6, and 8 to measure changes in subject's reported side effects during the trial.
viii) Laboratory tests including; Serum levels of mood stabiliser, LH, FSH, Estrogen, Progesterone, Prolactin, DHEA,Testosterone and(Baseline and evaluation visits).
详细描述
This research protocol outlines a multi-site clinical trial of adjunctive estradiol in women with Schizophrenia. We propose to recruit 180 women into this study from 3 Australian sites - The Alfred Hospital, Barwon Health, and Dandenong Hospital.
1.1 Literature Review
Schizophrenia is a severe mental disorder that affects up to 2% of the adult population. Patients present with a variety of symptoms including hallucinations, delusions and bizarre behaviour while some develop additional "negative" symptoms such as amotivational states and poverty of thought.
Schizophrenia is generally thought to be an organic brain disorder with psychosocial determinants for course and outcome. The illness appears to be heterogenous with groups of patients presenting with distinct and differing patterns of psychopathology and illness course. Part of this heterogeneity includes distinct male and female subtypes of schizophrenia.
In recent times, gender differences in schizophrenia have received some attention, in particular from an epidemiological and psychopathological perspective. Hormonal studies have been utilised to investigate underlying neuroendocrine disturbances in schizophrenia, but information from these studies has not been used in the development of new gender specific treatment strategies. Overall the treatment of schizophrenia has remained gender-blind. The main gender differences observed in schizophrenia that have international consensus include the later age of onset in women; better response to antipsychotics in women; and more treatment resistant negative symptoms in men. Women have also demonstrated vulnerability to psychotic episodes during menopause, the post-partum period and at low estrogen phases of the menstrual cycle.
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 50 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Female participants of potential child-bearing age (Pre-menopausal and Post-menarche)
- •Female participants who meet the MINI (Mini International Neuropsychiatric Interview for DSM-IV) diagnostic criteria for current psychotic disorder or have a current DSM-IV diagnosis of Schizophrenia, Schizophreniform Disorder, or Schizoaffective Disorder (not in manic phase).
- •Female participants with a PANSS positive score greater than 15 and/or a PANSS negative score greater than
- •Female participants who are able to give informed consent
- •Female participants receiving 2-20mg daily Risperidone equivalents for at least 4 weeks.
排除标准
- •Female participants who are pregnant or lactating.
- •Female participants with known severe abnormalities in the hypothalamo-pituitary gonadal axis, thyroid dysfunction, central nervous system tumours, history of thromboembolic disorders, severe renal failure, severe hepatic failure, cardiac disease, epilepsy or other serious medical conditions which would contraindicate estrogen use.
- •Female participants already taking oral estrogen preparations containing greater then 30mcg estradiol.
- •Post-menopausal or pre-menarche female participants.
- •Female participants whose psychotic illness meets DSM-IV criteria for substance-induced psychotic disorder.
- •Female participants who have a current diagnosis of Schizoaffective Disorder and are in a manic phase.
研究组 & 干预措施
1
100 mcg Estradiol
干预措施: Estradiol (Drug)
2
200 mcg Estradiol
干预措施: Estradiol (Drug)
3
adjunctive transdermal placebo
干预措施: placebo (Other)
结局指标
主要结局
Positive and Negative Syndrome Scale (PANSS)
时间窗: Baseline and week 8
The Positive and Negative Syndrome Scale (PANSS) is a well validated, standardized method of evaluating and monitoring psychotic symptoms. The PANSS assesses: positive (hallucinations, delusions, thought disorder), negative (blunted affect, abstract thinking and general symptomatology. The positive and negative subscale each consist of 7 items rated from 1(absent) - 7(extreme) with a minimum score = 7, maximum score = 49. The general subscale consists of 16 items with a minimum score = 16, maximum score = 112. A Total PANSS score (positive+ negative + general scores) has a minimum of 30 and maximum of 210. Higher scores represent more severity in symptoms.
次要结局
- Scores on MADRS at Trial Completion(Baseline and week 8)
- Cognitive Performance (RBANS Scores)(baseline and week 8)
- Change in Hormone Levels Over Trial Duration(Baseline and weeks 1, 4 and 8.)
- Scores on Adverse Symptom Checklist at Trial Completion(Baseline and weeks 1, 2, 4, 6, 8)
研究者
Jayashri Kulkarni, Professor
Director
The Alfred