The Effect of Melatonin on Depression, Anxiety, Cognitive Function and Sleep Disturbances in Breast Cancer Patients
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 54
- 试验地点
- 1
- 主要终点
- Intention to Treat (Underestimate) - Depression at One Point in the Study Period
研究概览
简要总结
The purpose of this study is to investigate the effect of 6 mg melatonin daily for 1 week preoperatively to 12 weeks postoperatively on depressive symptoms, anxiety, cognitive function and sleep disturbances in breast cancer patients. Furthermore the investigators will examine whether a specific clock-gene (HPER3) is correlated with an increased risk of depression, sleep disturbances or cognitive dysfunction.
详细描述
About 1.4 million women are diagnosed with breast cancer every year. Breast cancer is the most common malignancy among women worldwide constituting about 1/5 of all cancer types. Breast cancer diagnosis and treatment, and the months following primary therapy are stressful times for most women. Aside from the actual "cancer threat" many women experience various degrees of depression, anxiety, sleep disturbances and memory/concentration problems (cognitive dysfunction). Naturally these factors influence the quality of life but also contribute to morbidity and mortality.
Melatonin is a regulatory circadian hormone having, among others, hypnotic, sedative, anxiolytic and possibly anti-depressive effects. It has very low toxicity and very few adverse effects.
The purpose of this project is to test melatonin (6 mg daily for 1 week preoperatively to 12 weeks postoperatively) on breast cancer patients and hopefully hereby be able to prevent depression, anxiety, sleep disturbances and cognitive dysfunction. On an overall perspective this will hopefully contribute to improving the quality of life for these patients and extend their lifetime. Furthermore the investigators will be examining whether a specific gene called a clock-gene (HPER3) is correlated with an increased risk of depression, sleep disturbances or cognitive dysfunction. If this is the case it could become possible to identify women with an increased risk and provide prophylactic treatment for those with a risk of developing a depression, sleep disturbances or cognitive disturbances.
Sample size calculations were based on our primary outcome parameter. Using a conservative estimate for the incidence of depression, the investigators expect to find a reduction from 30% to 15% with melatonin treatment. Sample size is sufficient to include our secondary and tertiary outcome parameters as well. The sample size calculations were calculated with a power of 80%, a type I error of 5% and a type II error of 20%.
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
- 30 Years 至 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Women, age 30-75, with breast cancer who are admitted for a lumpectomy or mastectomy at Herlev Hospital
- •ASA score I-III
- •No sign of depression measured my Major Depression Inventory (MDI)
- •Not pregnant
排除标准
- •Neoadjuvant chemotherapy
- •Treatment with SSRI, Warfarin or other anticoagulants (except 75 mg ASA daily), MAO inhibitors or calcium blockers
- •Rotor or Dubin-Johnson syndrome
- •Known allergic reaction to melatonin
- •Known and treated sleep apnea
- •Diabetes Mellitus - insulin treated
- •Ongoing or previous medically treated depression or bipolar disorder
- •Known autoimmune diseases - systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and sclerose
- •Incompensated liver cirrhosis
- •Severe kidney disease
- •Previous or current cancer
- •Known medically treated sleep-disorder (insomnia, restless legs etc)
- •Shift-work and night-work
- •Daily alcohol intake of more than 5 units
- •Pre-operative treatment with psychopharmacological drugs, opioids or anxiolytics (including all sleeping pills)
- •Predicted bad compliance
- •Pregnant or breast-feeding
- •Pre-operative Mini Mental State Evaluation (MMSE) score less than 24
研究组 & 干预措施
Melatonin
6 mg oral melatonin daily
干预措施: Melatonin (N-acetyl-5-methoxytryptamine) (Drug)
Placebo
6 mg oral placebo daily
干预措施: Placebo (Drug)
结局指标
主要结局
Intention to Treat (Underestimate) - Depression at One Point in the Study Period
时间窗: Intention to treat (underestimate) - depression at one point in the study period (not baseline)
MDI is a self-rating depression scale with 12 questions. MDI has previously been investigated in a Danish population. On a six-point Likert scale, the items measure how much time the symptoms have been present during the last 14 days. MDI is scored according to specific guidelines and can be used either as a rating scale or diagnostic instrument. For inclusion we used the diagnostic instrument (depression was an exclusion criteria) and for all other MDI measurements we used the rating scale. Rating scale: No depression - score from 0-20 Mild depression - score from 21-25 Moderate depression - score from 26-30 Severe depression - score from 31-50 For this analysis all missing MDI data have been analyzed as "NO" depression.
Intention to Treat (Overestimate) - Depression at One Point in the Study Period
时间窗: Intention to treat (overestimate) - depression at one point in the study period (not baseline)
MDI is a self-rating depression scale with 12 questions. MDI has previously been investigated in a Danish population. On a six-point Likert scale, the items measure how much time the symptoms have been present during the last 14 days. MDI is scored according to specific guidelines and can be used either as a rating scale or diagnostic instrument. For inclusion we used the diagnostic instrument (depression was an exclusion criteria) and for all other MDI measurements we used the rating scale. Rating scale: No depression - score from 0-20 Mild depression - score from 21-25 Moderate depression - score from 26-30 Severe depression - score from 31-50 For this analysis all missing MDI data have been analyzed as "YES" for depression.
Major Depression Inventory (MDI)- Depression at One Point in the Study
时间窗: Depression at one point in the study (not including baseline) out of 4 measurements at app. day 21, day 35, day 63 and day 91 of the study.
MDI is a self-rating depression scale with 12 questions. MDI has previously been investigated in a Danish population. On a six-point Likert scale, the items measure how much time the symptoms have been present during the last 14 days. MDI is scored according to specific guidelines and can be used either as a rating scale or diagnostic instrument. For inclusion we used the diagnostic instrument (depression was an exclusion criteria) and for all other MDI measurements we used the rating scale. Diagnostic scale using the ICD-10 algorithm: Mild depression: 2 core symptoms and 2 other symptoms Moderate depression: 2 core symptoms and 4 other symptoms Severe depression: 3 core symptoms and 5 other symptoms Rating scale: No depression - score from 0-20 Mild depression - score from 21-25 Moderate depression - score from 26-30 Severe depression - score from 31-50
Per Protocol - Depression at One Point in the Study Period
时间窗: Per protocol - depression at one point in the study period (not baseline)
MDI is a self-rating depression scale with 12 questions. MDI has previously been investigated in a Danish population. On a six-point Likert scale, the items measure how much time the symptoms have been present during the last 14 days. MDI is scored according to specific guidelines and can be used either as a rating scale or diagnostic instrument. For inclusion we used the diagnostic instrument (depression was an exclusion criteria) and for all other MDI measurements we used the rating scale. Rating scale: No depression - score from 0-20 Mild depression - score from 21-25 Moderate depression - score from 26-30 Severe depression - score from 31-50 This analysis includes only patients who have taken study medication as planned.
次要结局
- Area Under the Curve (AUC) for Data on Sleepiness (KSS) - Immediate Postoperative Period(Daily from inclusion till 8 days postoperatively)
- Area Under the Curve (AUC) for VAS Data on Pain - Long-term Postoperative Period(App. 14 days postoperatively till 10 weeks postoperatively)
- Area Under the Curve (AUC) for VAS Data on Anxiety - Immediate Postoperative Period(Daily - from inclusion till 8 days postoperatively)
- Area Under the Curve (AUC) for VAS Data on Anxiety - Long-term Postoperative Period(App. 14 days postoperatively till 10 weeks postoperatively)
- Area Under the Curve (AUC) for VAS Data on General Well-being - Long-term Postoperative Period(App. 14 days postoperatively till 10 weeks postoperatively)
- Area Under the Curve (AUC) for VAS Data on Fatigue - Long-term Postoperative Period(App. 14 days postoperatively till 10 weeks postoperatively)
- Area Under the Curve (AUC) for VAS Data on Sleep Quality - Long-term Postoperative Period(App. 14 days postoperatively till 10 weeks postoperatively)
- Area Under the Curve (AUC) for Data on Sleepiness (KSS) - Long-term Postoperative Period(App. 14 days postoperatively till 10 weeks postoperatively)
- Area Under the Curve (AUC) for VAS Data on Fatigue - Immediate Postoperative Period(Daily from inclusion till 8 days postoperatively)
- Area Under the Curve (AUC) for Data on General Well-being - Immediate Postoperative Period(Daily from inclusion till 8 days postoperatively)
- HPER3 Genotype(At inclusion = day-7)
- Area Under the Curve (AUC) for VAS Data on Pain - Immediate Postoperative Period(Daily from inclusion till 8 days postoperatively)
- Area Under the Curve (AUC) for VAS Data on Sleep Quality - Immediate Postoperative Period(Daily from inclusion till 8 days postoperatively)
- Sleep Architecture(From inclusion till 14 days postoperatively)
- Incidence of Postoperative Cognitive Dysfunction (POCD) App. 10 Weeks Postoperatively(App. 10 weeks postoperatively)
- Incidence of Postoperative Cognitive Dysfunction (POCD) App. 2 Weeks Postoperatively.(App. 2 weeks postoperatively)
研究者
Melissa Voigt Hansen
M.D., ph-D student
Herlev Hospital