The Effect of Melatonin on Depression, Anxiety, Cognitive Function and Sleep Disturbances in Breast Cancer Patients (MELODY)

This study has been terminated.
(Inclusion rate not as expected. Not financially possible to involve other centres.)
Sponsor:
Collaborators:
University of Copenhagen
Rigshospitalet, Denmark
Pharma Nord
Information provided by (Responsible Party):
Melissa Voigt Hansen, Herlev Hospital
ClinicalTrials.gov Identifier:
NCT01355523
First received: May 13, 2011
Last updated: March 7, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Depression
Drug: Melatonin (N-acetyl-5-methoxytryptamine)
Drug: Placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Effect of Melatonin on Depression, Anxiety, Cognitive Function and Sleep Disturbances in Breast Cancer Patients

Resource links provided by NLM:


Further study details as provided by Herlev Hospital:

Primary Outcome Measures:
  • Major Depression Inventory (MDI) [ Time Frame: App. 1 week pre-operatively = day -7 ] [ Designated as safety issue: No ]
    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 as a rating scale/diagnostic instrument. When used as a diagnostic instrument patients are classified as mild, moderate or severe depression or no depression.

  • MDI [ Time Frame: App. 2 weeks postoperatively = day 14 ] [ Designated as safety issue: No ]
    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 as a rating scale/diagnostic instrument. When used as a diagnostic instrument patients are classified as mild, moderate or severe depression or no depression.

  • MDI [ Time Frame: App. 4 weeks postoperatively = day 28 ] [ Designated as safety issue: No ]
    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 as a rating scale/diagnostic instrument. When used as a diagnostic instrument patients are classified as mild, moderate or severe depression or no depression.

  • MDI [ Time Frame: App. 8 weeks postoperatively = day 56 ] [ Designated as safety issue: No ]
    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 as a rating scale/diagnostic instrument. When used as a diagnostic instrument patients are classified as mild, moderate or severe depression or no depression.

  • MDI [ Time Frame: App. 12 weeks postoperatively = day 84 ] [ Designated as safety issue: No ]
    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 as a rating scale/diagnostic instrument. When used as a diagnostic instrument patients are classified as mild, moderate or severe depression or no depression.


Secondary Outcome Measures:
  • Anxiety [ Time Frame: Daily - from inclusion till 14 days postoperatively ] [ Designated as safety issue: No ]
    Anxiety measured by VAS (visual analog scale)

  • Sleep architecture [ Time Frame: From inclusion till 14 days postoperatively ] [ Designated as safety issue: No ]
    Actigraphy (total minutes asleep, sleep effectiveness, sleep latency, awakenings). A wrist actigraph will be worn from inclusion till 14 days postoperatively.

  • Cognitive function [ Time Frame: App. 1 week preoperatively = day-7 ] [ Designated as safety issue: No ]
    Domaine specific changes in cognitive function measured by ISPOCD (International Study of Post-Operative Cognitive Dysfunction) neuropsychological test-battery.

  • Cognitive function [ Time Frame: App. 2 weeks postoperatively = day 14 ] [ Designated as safety issue: No ]
    Domaine specific changes in cognitive function measured by ISPOCD (International Study of Post-Operative Cognitive Dysfunction) neuropsychological test-battery.

  • Cognitive function [ Time Frame: App. 12 weeks postoperatively = day 84 ] [ Designated as safety issue: No ]
    Domaine specific changes in cognitive function measured by ISPOCD (International Study of Post-Operative Cognitive Dysfunction) neuropsychological test-battery.

  • HPER3 genotype [ Time Frame: At inclusion = day-7 ] [ Designated as safety issue: No ]
    A blood sample will be taken at inclusion and analysed for HPER3 genotype (4/4, 4/5, 5/5) and this will be investigated for a correlation with sleep, cognitive function and depressive symptoms

  • Sleep [ Time Frame: Daily from inclusion till 14 days postoperatively ] [ Designated as safety issue: No ]
    Subjective sleep score on Visual Analog Scale. Sleepiness measured by Karolinska Sleepiness Scale. A sleep-diary recording sleep quantity of day and night sleep. Completed daily.

  • Sleep [ Time Frame: App. 14 days postoperatively till 12 weeks postoperatively ] [ Designated as safety issue: No ]
    Subjective sleep on a Visual Analog Scale. Sleepiness measured by Karolinska Sleepiness Scale. A sleep-diary recording sleep quantity of day and night sleep. Completed every 14th day.

  • Fatigue [ Time Frame: Daily from inclusion till 14 days postoperatively ] [ Designated as safety issue: No ]
    Fatigue on a Visual Analog Scale - filled out daily.

  • Fatigue [ Time Frame: App. 14 days postoperatively till 12 weeks postoperatively ] [ Designated as safety issue: No ]
    Fatigue on a Visual Analog Scale - filled out every 14th day.

  • General well-being [ Time Frame: Daily from inclusion till 14 days postoperatively ] [ Designated as safety issue: No ]
    Generel well-being on a Visual Analog Scale - filled out daily.

  • General well-being [ Time Frame: App. 14 days postoperatively till 12 weeks postoperatively ] [ Designated as safety issue: No ]
    General well-being on a Visual Analog Scale - filled out every 14th day.

  • Pain [ Time Frame: Daily from inclusion till 14 days postoperatively ] [ Designated as safety issue: No ]
    Pain on a Visual Analog Scale - filled out daily.

  • Pain [ Time Frame: App. 14 days postoperatively till 12 weeks postoperatively ] [ Designated as safety issue: No ]
    Pain on a Visual Analog Scale - filled out every 14th day.

  • Anxiety [ Time Frame: App. 14 days postoperatively till 12 weeks postoperatively ] [ Designated as safety issue: No ]
    Anxiety measured by VAS (visual analog scale). Completed every 14th day.


Enrollment: 54
Study Start Date: July 2011
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Melatonin
6 mg oral melatonin daily
Drug: Melatonin (N-acetyl-5-methoxytryptamine)
6 mg oral melatonin daily 1 hour before bedtime
Other Names:
  • Melatonin
  • N-acetyl-5-methoxytryptamin
Placebo Comparator: Placebo
6 mg oral placebo daily
Drug: Placebo
6 mg oral placebo daily 1 hour before bedtime

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

Ages Eligible for Study:   30 Years to 75 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01355523

Locations
Denmark
Herlev Hospital
Copenhagen, Denmark, 2730
Sponsors and Collaborators
Melissa Voigt Hansen
University of Copenhagen
Rigshospitalet, Denmark
Pharma Nord
Investigators
Principal Investigator: Melissa V Hansen, MD Herlev Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Melissa Voigt Hansen, M.D., ph-D student, Herlev Hospital
ClinicalTrials.gov Identifier: NCT01355523     History of Changes
Other Study ID Numbers: MVH-03, 2010-022460-12, 2007-58-0015/HEH.750.89-12, H-4-2011-007
Study First Received: May 13, 2011
Last Updated: March 7, 2013
Health Authority: Denmark: Danish Dataprotection Agency
Denmark: The Danish National Committee on Biomedical Research Ethics
Denmark: Danish Medicines Agency

Keywords provided by Herlev Hospital:
Breast cancer surgery
Melatonin
Depression
Anxiety
Sleep disturbances
Cognitive function

Additional relevant MeSH terms:
Anxiety Disorders
Breast Neoplasms
Depression
Depressive Disorder
Sleep Disorders
Dyssomnias
Parasomnias
Mental Disorders
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Behavioral Symptoms
Mood Disorders
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Melatonin
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents

ClinicalTrials.gov processed this record on April 22, 2014