Clinical trial NCT01355523: The Effect of Melatonin on Depression, Anxiety, Cognitive Function and Sleep Disturbances in Breast Cancer Patients
Official title: The Effect of Melatonin on Depression, Anxiety, Cognitive Function and Sleep Disturbances in Breast Cancer Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Breast Cancer
Depression
Keywords: Breast cancer surgery
Melatonin
Depression
Anxiety
Sleep disturbances
Cognitive function
Lead sponsor: Herlev Hospital
Sponsor class: OTHER
Collaborators: name: University of Copenhagen
name: Rigshospitalet, Denmark
name: Pharma Nord
First posted: 2011-05-18
Enrollment: 54
Sex: FEMALE
Minimum age (years): 30
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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%.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* Neoadjuvant chemotherapy
* Treatment with SSRI, Warfarin or other anticoagulants (except 75 mg ASA daily), MAO inhibitors or calcium blockers
* Rotor or Dubin-Johnson syndrome
* Epilepsy
* 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

Primary outcomes:
measure: Major Depression Inventory (MDI)- Depression at One Point in the Study
timeFrame: 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.
measure: Per Protocol - Depression at One Point in the Study Period
timeFrame: Per protocol - depression at one point in the study period (not baseline)
measure: Intention to Treat (Underestimate) - Depression at One Point in the Study Period
timeFrame: Intention to treat (underestimate) - depression at one point in the study period (not baseline)
measure: Intention to Treat (Overestimate) - Depression at One Point in the Study Period
timeFrame: Intention to treat (overestimate) - depression at one point in the study period (not baseline)
Secondary outcomes:
measure: Area Under the Curve (AUC) for VAS Data on Anxiety - Immediate Postoperative Period
timeFrame: Daily - from inclusion till 8 days postoperatively
measure: Area Under the Curve (AUC) for VAS Data on Anxiety - Long-term Postoperative Period
timeFrame: App. 14 days postoperatively till 10 weeks postoperatively
measure: Area Under the Curve (AUC) for Data on Sleepiness (KSS) - Immediate Postoperative Period
timeFrame: Daily from inclusion till 8 days postoperatively
measure: Area Under the Curve (AUC) for Data on Sleepiness (KSS) - Long-term Postoperative Period
timeFrame: App. 14 days postoperatively till 10 weeks postoperatively
measure: Area Under the Curve (AUC) for VAS Data on Fatigue - Immediate Postoperative Period
timeFrame: Daily from inclusion till 8 days postoperatively
measure: Area Under the Curve (AUC) for VAS Data on Fatigue - Long-term Postoperative Period
timeFrame: App. 14 days postoperatively till 10 weeks postoperatively
measure: Area Under the Curve (AUC) for Data on General Well-being - Immediate Postoperative Period
timeFrame: Daily from inclusion till 8 days postoperatively
measure: Area Under the Curve (AUC) for VAS Data on General Well-being - Long-term Postoperative Period
timeFrame: App. 14 days postoperatively till 10 weeks postoperatively
measure: Area Under the Curve (AUC) for VAS Data on Pain - Immediate Postoperative Period
timeFrame: Daily from inclusion till 8 days postoperatively
measure: Area Under the Curve (AUC) for VAS Data on Pain - Long-term Postoperative Period
timeFrame: App. 14 days postoperatively till 10 weeks postoperatively
measure: Area Under the Curve (AUC) for VAS Data on Sleep Quality - Immediate Postoperative Period
timeFrame: Daily from inclusion till 8 days postoperatively
measure: Area Under the Curve (AUC) for VAS Data on Sleep Quality - Long-term Postoperative Period
timeFrame: App. 14 days postoperatively till 10 weeks postoperatively
measure: Sleep Architecture
timeFrame: From inclusion till 14 days postoperatively
measure: HPER3 Genotype
timeFrame: At inclusion = day-7
measure: Incidence of Postoperative Cognitive Dysfunction (POCD) App. 2 Weeks Postoperatively.
timeFrame: App. 2 weeks postoperatively
measure: Incidence of Postoperative Cognitive Dysfunction (POCD) App. 10 Weeks Postoperatively
timeFrame: App. 10 weeks postoperatively
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Herlev Hospital
Study officials:
affiliation: Herlev Hospital
name: Melissa V Hansen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hansen MV, Madsen MT, Andersen LT, Hageman I, Rasmussen LS, Bokmand S, Rosenberg J, Gogenur I. Effect of Melatonin on Cognitive Function and Sleep in relation to Breast Cancer Surgery: A Randomized, Double-Blind, Placebo-Controlled Trial. Int J Breast Cancer. 2014;2014:416531. doi: 10.1155/2014/416531. Epub 2014 Aug 27.