Anti-Estrogens - A Potential Treatment for Bipolar Affective Disorder in Women?
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 51
- 试验地点
- 1
- 主要终点
- Scores on CARS-M Scale at trial completion
研究概览
简要总结
OBJECTIVE:
To test the use of two adjunctive hormonal agents in a 28 day three-arm, double-blind, placebo-controlled study in the treatment of acute mania/hypomania.
HYPOTHESIS:
That women receiving adjunctive Tamoxifen or Progesterone will demonstrate a more rapid and more substantial decrease in manic symptoms over the course of the study than women receiving adjunctive placebo.
STUDY POPULATION:
Sixty females with a current diagnosis of Bipolar Affective Disorder or Schizoaffective disorder - Manic Phase, according to the operationalised criteria of the Diagnostic and Statistical Manual, 4th edition (DSM-IV) of the American Psychiatric Association.
STUDY MEDICATION:
Tamoxifen. One third of patients (twenty) will be randomized to receive adjunctive Tamoxifen at 40 mg/day for 28 days. The Tamoxifen will be administered within a plain capsule to maintain "blinding" of treatment arm.
Progesterone. One third of patients (twenty) will be randomized to receive adjunctive oral Provera (progesterone) at 20 mg/day. The Progesterone will be administered within a plain capsule identical to that used with Tamoxifen.
Placebo. The remaining one third of patients will be randomized to receive adjunctive placebo (inert substance). The placebo substance will be administered within a plain capsule identical to that used with Tamoxifen and Progesterone.
STUDY EVALUATIONS:
Data will be collected over a 28-day period for each patient. Visits will be performed at baseline, and then at weekly intervals. A total of five visits will be completed for each patient. The following evaluations will be performed:
- Psychiatric evaluation to determine diagnosis. (Baseline visit only)
- General clinical evaluation including medical history, current conditions and a non-invasive physical examination, body weight, vital signs. (Baseline visit only)
- Medication history (baseline and evaluation visits).
- Demographics (baseline visits only).
- Completion of clinical rating scales; CARS-M, PANSS, MADRS, AIMS, Barnes Akathisia scale (BA), and Simpson-Angus scale (SA) (baseline and evaluation visits). A Menstrual Cycle Interview and a cognitive assessment (RBANS) will be performed at baseline and endpoint (day 28) visit.
- Laboratory tests including; Serum levels of mood stabilizer, luteinizing hormone (LH), follicle-stimulating hormone (FSH), Estrogen, Progesterone, Prolactin, dehydroepiandrosterone (DHEA), Testosterone and protein kinase C(PKC) (baseline and evaluation visits).
- Inclusion/exclusion checklist (baseline visit only).
- Informed consent (baseline visit only).
详细描述
BACKGROUND:
Bipolar Affective Disorder remains an illness with high morbidity and mortality. Mood stabilizers such as lithium and sodium valproate have been described as having their anti-manic effect by targeting protein kinase C (PKC) isozymes (Manji and Lenos, 1999). In rats chronically treated with lithium, there is a reduction of the major PKC substrate MARCKS and a reduction in the hippocampus of the expression of two protein kinase isozymes, alpha and epsilon. Manji et al. (1999) further postulated that PKC inhibitors such as tamoxifen and other estrogen antagonists might represent a novel class of therapeutic agents for the treatment of mania.
Clinical support for the use of "anti-estrogens" in treating mania are found in case reports such as Nelson (1998), and Goldstein (1986), describing the use of danazol in a case of mania, and by Chouinard et al (1987) describing the use of estrogen and progesterone in a case of mania.
A recent preliminary trial by Bebchuk et al, (2000), demonstrated that adjunctive tamoxifen improved in manic symptoms in seven patients. A limitation of their trial was that they failed to standardise the other treatment agents used, which included lithium, antidepressants, anxiolytic and anti-psychotic medications. Mania in women is also noted to have cyclic variations, which is poorly documented and largely anecdotal. This needs further study, and since there is a preponderance of affective disorder in women, we propose conducting a study in women with active symptoms of mania.
OBJECTIVES OF THE STUDY PRIMARY OBJECTIVE To test and compare the use of two adjunctive hormonal agents in a 28 day three-arm double-blind, placebo-controlled study in the treatment of acute mania or hypomania.
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 patients who have a current diagnosis of Bipolar Affective Disorder (Manic phase) or Schizoaffective Disorder (Bipolar type in manic phase).
- •Female patients who are able to give informed consent.
排除标准
- •Female patients who are pregnant or lactating.
- •Female patients with postpartum psychosis or related disorder.
- •Female patients with known abnormalities in the hypothalamo-pituitary gonadal-axis, thyroid dysfunction, central nervous system tumors.
- •Female patients taking estrogen preparations such as the oral contraceptive pill.
- •Female patients currently taking interacting drugs including warfarin, aminoglutethimide, diuretics, methyldopa, theophylline, fluoxetine, calcium channel blockers and non-steroidal anti-inflammatory drugs.
- •Female patients whose psychotic illness is directly due to illicit drugs or who have a history of substance abuse or dependence during the last 6 months.
- •Females with any significant unstable medical illness such as cardiovascular disease, renal disease, Addisons disease, thromboembolic disorders, epilepsy, diabetes etc.
研究组 & 干预措施
1
Tamoxifen 40 mg daily
干预措施: Tamoxifen (Drug)
2
Progesterone 20 mg daily
干预措施: Progesterone (Drug)
3
Placebo daily
干预措施: placebo (Other)
结局指标
主要结局
Scores on CARS-M Scale at trial completion
时间窗: Baseline and weeks 1, 2, 3 and 4
次要结局
- Scores on PANSS at trial completion (4 weeks)(Baseline and weeks 1, 2, 3 and 4)
- Scores on MADRS at trial completion (4 weeks)(Baseline and weeks 1, 2, 3 and 4)
- Scores on Adverse Symptom Checklist at trial completion (4 weeks)(Baseline and weeks 1, 2, 3 and 4)
- Change in hormone levels over trial duration(Baseline and weeks 1, 2, 3 and 4)
- Scores on RBANS at trial completion (4 weeks)(Baseline and week 4)