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

NCT01355523 | Terminated Phase 2 Results

• 4 other identifiers: MVH-032010-022460-122007-58-0015/HEH.750.89-12H-4-2011-007
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer; Depression

Keywords

Breast cancer surgery; Melatonin; Depression; Anxiety; Sleep disturbances; Cognitive function

Outcome Measures

Primary Outcomes (4)

• Major Depression Inventory (MDI)- Depression at One Point in 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

  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.

• Per Protocol - Depression at One Point in the Study Period

  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.

  Per protocol - depression at one point in the study period (not baseline)

• Intention to Treat (Underestimate) - Depression at One Point in the Study Period

  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 (underestimate) - depression at one point in the study period (not baseline)

• Intention to Treat (Overestimate) - Depression at One Point in the Study Period

  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.

  Intention to treat (overestimate) - depression at one point in the study period (not baseline)

Secondary Outcomes (16)

• 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 Data on Sleepiness (KSS) - Immediate Postoperative Period

  Daily from inclusion till 8 days 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

Study Arms (2)

Melatonin

ACTIVE COMPARATOR

6 mg oral melatonin daily

Drug: Melatonin (N-acetyl-5-methoxytryptamine)

Placebo

PLACEBO COMPARATOR

6 mg oral placebo daily

Drug: Placebo

Interventions

Melatonin (N-acetyl-5-methoxytryptamine) DRUG

6 mg oral melatonin daily 1 hour before bedtime

Also known as: Melatonin, N-acetyl-5-methoxytryptamin

Melatonin

Placebo DRUG

6 mg oral placebo daily 1 hour before bedtime

Placebo

Eligibility Criteria

• Age: 30 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Melissa Voigt Hansen: lead
• University of Copenhagen: collaborator
• Rigshospitalet, Denmark: collaborator
• Pharma Nord: collaborator

Study Sites (1)

Herlev Hospital

Copenhagen, 2730, Denmark

Location

Related Publications (1)

• 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.

  PMID: 25328711 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Depression; Anxiety Disorders; Parasomnias

Interventions

Melatonin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Behavioral Symptoms; Behavior; Mental Disorders; Sleep Wake Disorders; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Tryptamines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Limitations and Caveats

Premature termination (54/260). Only included about 8% (54/703) of the patients assessed for eligibility.

Results Point of Contact

• Title: MD Melissa Voigt Hansen
• Organization: Herlev Hospital, Department of Surgery

melissa.voigt.hansen@regionh.dk

+45 20661119

Study Officials

• Melissa V Hansen, MD

  Herlev Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: M.D., ph-D student

Study Record Dates

• First Submitted: May 13, 2011
• First Posted: May 18, 2011
• Study Start: July 1, 2011
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: May 6, 2014
• Results First Posted: May 6, 2014

Record last verified: 2014-04

Locations

DK (1)