Breast CancerPhase 2/3MELODYNCT01355523
The Effect of Melatonin on Depression, Anxiety, Cognitive Function and Sleep Disturbances in Breast Cancer Patients
A Phase 2/3 study testing Melatonin (N-acetyl-5-methoxytryptamine) in people with Breast Cancer and Depression, run by Melissa Voigt Hansen at 1 site in Denmark.
Trial 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. Read more about this study
- Who is it for?
- Ages 30 to 75 years, women only
- Conditions the study is for
- Breast Cancer, Depression
- What is being tested?
- Melatonin (N-acetyl-5-methoxytryptamine)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 54 participants
- Where
- 1 siteDenmark
- Study dates
- Jul 2011to Jan 2013
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 75 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 19Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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%.
- Conditions
- Breast Cancer, Depression
- Being tested
- Melatonin (N-acetyl-5-methoxytryptamine), Placebo
- Keywords
- Breast cancer surgery, Melatonin, Depression, Anxiety, Sleep disturbances, Cognitive function
- Medical subject headings
- Breast Neoplasms, Depression, Anxiety Disorders, Parasomnias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Melatonin (N-acetyl-5-methoxytryptamine)Drug
Also called Melatonin, N-acetyl-5-methoxytryptamin
6 mg oral melatonin daily 1 hour before bedtime
PlaceboDrug
6 mg oral placebo daily 1 hour before bedtime
| Study group | Role | What they receive |
|---|---|---|
| Melatonin | Active comparator | 6 mg oral melatonin daily Receives: Drug: Melatonin (N-acetyl-5-methoxytryptamine) |
| Placebo | Placebo comparator | 6 mg oral placebo daily Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Anxiety measured by VAS (visual analog scale). A subjective feeling of anxiety was registered on a VAS going from "no anxiety", equivalent to 0mm to "worst possible anxiety", equivalent to 100mm.
Patients were only included in the analysis if they had completed daily VAS on anxiety, sleep quality, general well-being, fatigue, pain and sleepiness for at least 8 days postoperatively.
Single missing data were filled out using last observation carried forward (LOCF). % of cases filled out by LOCF < 2 %
Measured: Daily - from inclusion till 8 days postoperatively
Area Under the Curve (AUC) for VAS Data on Anxiety - Long-term Postoperative Period
Anxiety measured by VAS (visual analog scale). Completed every 14th day. A subjective feeling of anxiety was registered on a VAS going from "no anxiety", equivalent to 0mm to "worst possible anxiety", equivalent to 100mm.
Patients were only included in the analysis if they had completed VAS on anxiety, sleep quality, general well-being, fatigue, pain and sleepiness in the long-term postoperative period (every 14th day).
Single missing data were filled out using last observation carried forward (LOCF). % of cases filled out by LOCF < 1 %
Measured: App. 14 days postoperatively till 10 weeks postoperatively
Area Under the Curve (AUC) for Data on Sleepiness (KSS) - Immediate Postoperative Period
Sleepiness measured by Karolinska Sleepiness Scale. KSS is a 9-point scale from 1 (very awake) to 9 (very sleepy) where a score of 7 or more reflects pathological sleepiness.
Patients were only included in the analysis if they had completed daily VAS on anxiety, sleep quality, general well-being, fatigue, pain and sleepiness for at least 8 days postoperatively.
Single missing data were filled out using last observation carried forward (LOCF). % of cases filled out by LOCF < 2 %
Measured: Daily from inclusion till 8 days postoperatively
Area Under the Curve (AUC) for Data on Sleepiness (KSS) - Long-term Postoperative Period
Sleepiness measured by Karolinska Sleepiness Scale. KSS is a 9-point scale from 1 (very awake) to 9 (very sleepy) where a score of 7 or more reflects pathological sleepiness.
Patients were only included in the analysis if they had completed VAS on anxiety, sleep quality, general well-being, fatigue, pain and sleepiness in the long-term postoperative period (every 14th day).
Single missing data were filled out using last observation carried forward (LOCF). % of cases filled out by LOCF < 1 %
Measured: App. 14 days postoperatively till 10 weeks postoperatively
Area Under the Curve (AUC) for VAS Data on Fatigue - Immediate Postoperative Period
Fatigue on a Visual Analog Scale - filled out daily. A subjective feeling of fatigue was registered on a VAS going from "no fatigue", equivalent to 0mm to "worst possible fatigue", equivalent to 100mm.
Patients were only included in the analysis if they had completed daily VAS on anxiety, sleep quality, general well-being, fatigue, pain and sleepiness for at least 8 days postoperatively.
Single missing data were filled out using last observation carried forward (LOCF). % of cases filled out by LOCF < 2 %
Measured: Daily from inclusion till 8 days postoperatively
Area Under the Curve (AUC) for VAS Data on Fatigue - Long-term Postoperative Period
Fatigue on a Visual Analog Scale - filled out every 14th day. A subjective feeling of fatigue was registered on a VAS going from "no fatigue", equivalent to 0mm to "worst possible fatigue", equivalent to 100mm.
Patients were only included in the analysis if they had completed VAS on anxiety, sleep quality, general well-being, fatigue, pain and sleepiness in the long-term postoperative period (every 14th day).
Single missing data were filled out using last observation carried forward (LOCF). % of cases filled out by LOCF < 1 %
Measured: App. 14 days postoperatively till 10 weeks postoperatively
Area Under the Curve (AUC) for Data on General Well-being - Immediate Postoperative Period
General well-being on a Visual Analog Scale - filled out daily. A subjective feeling of general well-being was registered on a VAS going from "very high well-being", equivalent to 0mm to "very low well-being", equivalent to 100mm.
Patients were only included in the analysis if they had completed daily VAS on anxiety, sleep quality, general well-being, fatigue, pain and sleepiness for at least 8 days postoperatively.
Single missing data were filled out using last observation carried forward (LOCF). % of cases filled out by LOCF < 2 %
Measured: Daily from inclusion till 8 days postoperatively
Area Under the Curve (AUC) for VAS Data on General Well-being - Long-term Postoperative Period
General well-being on a Visual Analog Scale - filled out every 14th day. A subjective feeling of general well-being was registered on a VAS going from "very high well-being", equivalent to 0mm to "very low well-being", equivalent to 100mm.
Patients were only included in the analysis if they had completed VAS on anxiety, sleep quality, general well-being, fatigue, pain and sleepiness in the long-term postoperative period (every 14th day).
Single missing data were filled out using last observation carried forward (LOCF). % of cases filled out by LOCF < 1 %
Measured: App. 14 days postoperatively till 10 weeks postoperatively
Area Under the Curve (AUC) for VAS Data on Pain - Immediate Postoperative Period
Pain on a Visual Analog Scale - filled out daily. A subjective feeling of pain was registered on a VAS going from "no pain", equivalent to 0mm to "worst possible pain", equivalent to 100mm.
Patients were only included in the analysis if they had completed daily VAS on anxiety, sleep quality, general well-being, fatigue, pain and sleepiness for at least 8 days postoperatively.
Single missing data were filled out using last observation carried forward (LOCF). % of cases filled out by LOCF < 2 %
Measured: Daily from inclusion till 8 days postoperatively
Area Under the Curve (AUC) for VAS Data on Pain - Long-term Postoperative Period
Pain on a Visual Analog Scale - filled out every 14th day. A subjective feeling of pain was registered on a VAS going from "no pain", equivalent to 0mm to "worst possible pain", equivalent to 100mm.
Patients were only included in the analysis if they had completed VAS on anxiety, sleep quality, general well-being, fatigue, pain and sleepiness in the long-term postoperative period (every 14th day).
Single missing data were filled out using last observation carried forward (LOCF). % of cases filled out by LOCF < 1 %
Measured: App. 14 days postoperatively till 10 weeks postoperatively
Area Under the Curve (AUC) for VAS Data on Sleep Quality - Immediate Postoperative Period
Subjective sleep score on Visual Analog Scale. Subjective sleep quality was registered on a VAS going from "best possible sleep", equivalent to 0mm to "worst possible sleep", equivalent to 100mm.
Patients were only included in the analysis if they had completed daily VAS on anxiety, sleep quality, general well-being, fatigue, pain and sleepiness for at least 8 days postoperatively.
Single missing data were filled out using last observation carried forward (LOCF). % of cases filled out by LOCF < 2 %
Measured: Daily from inclusion till 8 days postoperatively
Area Under the Curve (AUC) for VAS Data on Sleep Quality - Long-term Postoperative Period
Subjective sleep on a Visual Analog Scale. Subjective sleep quality was registered on a VAS going from "best possible sleep", equivalent to 0mm to "worst possible sleep", equivalent to 100mm.
Patients were only included in the analysis if they had completed VAS on anxiety, sleep quality, general well-being, fatigue, pain and sleepiness in the long-term postoperative period (every 14th day).
Single missing data were filled out using last observation carried forward (LOCF). % of cases filled out by LOCF < 1 %
Measured: App. 14 days postoperatively till 10 weeks postoperatively
Sleep Architecture
Actigraphy (total minutes asleep, sleep effectiveness, sleep latency, awakenings). A wrist actigraph will be worn from inclusion till 14 days postoperatively.
Measured: From inclusion till 14 days postoperatively
HPER3 Genotype
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 7 patients did not give blood samples
Measured: At inclusion = day-7
Incidence of Postoperative Cognitive Dysfunction (POCD) App. 2 Weeks Postoperatively.
Calculations for POCD were based on normative data from 133 females aged 40-60 years. We evaluated changes from the preoperative baseline to the 2 postoperative test sessions. In controls we calculated mean and standard deviations (SD) of these differences. The mean change in this group may be taken as estimated learning effects. For the individual patients, we compared baseline scores with the 2- and 12-week postoperative test results, subtracted the average learning effect from the changes and divided the result by the SD of the control group to obtain a Z score for the 7 individual test outcomes. A large positive Z score indicated deterioration in cognitive function from baseline in patients. We defined a composite Z score as the sum of the 7 Z scores and normalized this using the SD for that sum in the controls. POCD was defined as a combined Z score >1.96 or a Z score >1.96 in at least 2 of the 7 subtests.
Units of measure = % of patients with YES to POCD
Measured: App. 2 weeks postoperatively
Incidence of Postoperative Cognitive Dysfunction (POCD) App. 10 Weeks Postoperatively
Calculations for POCD were based on normative data from 133 females aged 40-60 years. We evaluated changes from the preoperative baseline to the 2 postoperative test sessions. In controls we calculated mean and standard deviations (SD) of these differences. The mean change in this group may be taken as estimated learning effects. For the individual patients, we compared baseline scores with the 2- and 12-week postoperative test results, subtracted the average learning effect from the changes and divided the result by the SD of the control group to obtain a Z score for the 7 individual test outcomes. A large positive Z score indicated deterioration in cognitive function from baseline in patients. We defined a composite Z score as the sum of the 7 Z scores and normalized this using the SD for that sum in the controls. POCD was defined as a combined Z score >1.96 or a Z score >1.96 in at least 2 of the 7 subtests.
Units of measure = % of patients with YES to POCD
Measured: App. 10 weeks postoperatively
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2011 (estimated)
- Study startJul 2011
- Primary completionJan 2013
- Study completionJan 2013
Why it stopped: Inclusion rate not as expected. Not financially possible to involve other centres.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- Melissa Voigt Hansen
- Sponsor type
- University, hospital or other
- Collaborators
- University of Copenhagen, Copenhagen University Hospital, Rigshospitalet, Pharma Nord
- Responsible party
- Sponsor-investigator, Melissa Voigt Hansen, Herlev Hospital
- Investigators
- Melissa V Hansen, MD, Principal investigator, Herlev Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01355523
- Sponsor's protocol ID
- MVH-03
- Other IDs
- 2010-022460-12, 2007-58-0015/HEH.750.89-12, H-4-2011-007
- Acronym
- MELODY
- Status last verified
- Apr 2014
- First submitted
- 13 May 2011
- Last updated
- 6 May 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 25328711
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Melatonin on Depression, Anxiety, Cognitive Function and Sleep Disturbances in Breast Cancer Patients
- ClinicalTrials.gov ID
- NCT01355523
- Acronym / sponsor ID
- MELODY / MVH-03
- Conditions
- Breast Cancer, Depression
- Keywords
- Breast cancer surgery, Melatonin, Depression, Anxiety, Sleep disturbances, Cognitive function
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Inclusion rate not as expected. Not financially possible to involve other centres.
- Enrolment
- 54 participants (actual)
- Lead sponsor
- Melissa Voigt HansenUniversity, hospital or other
- Collaborators
- University of Copenhagen, Copenhagen University Hospital, Rigshospitalet, Pharma Nord
- Study start
- Jul 2011
- Primary completion
- Jan 2013 (actual)
- Study completion
- Jan 2013 (actual)
- First posted
- 18 May 2011 (estimated)
- Results
- Posted 6 May 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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%.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Melatonin | Active comparator | Drug: Melatonin (N-acetyl-5-methoxytryptamine)6 mg oral melatonin daily |
| Placebo | Placebo comparator | Drug: Placebo6 mg oral placebo daily |
Who may qualify
- Ages
- 30 to 75 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Melatonin (N-acetyl-5-methoxytryptamine)Also: Melatonin, N-acetyl-5-methoxytryptamin6 mg oral melatonin daily 1 hour before bedtime | Drug | Melatonin |
| Placebo6 mg oral placebo daily 1 hour before bedtime | Drug | Placebo |
Primary outcome
Major Depression Inventory (MDI)- Depression at One Point in the Study
Time frame: 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
Time frame: 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.
Intention to Treat (Underestimate) - Depression at One Point in the Study Period
Time frame: 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
Time frame: 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.
16 secondary outcomes
Area Under the Curve (AUC) for VAS Data on Anxiety - Immediate Postoperative Period
Time frame: Daily - from inclusion till 8 days postoperatively
Area Under the Curve (AUC) for VAS Data on Anxiety - Long-term Postoperative Period
Time frame: App. 14 days postoperatively till 10 weeks postoperatively
Area Under the Curve (AUC) for Data on Sleepiness (KSS) - Immediate Postoperative Period
Time frame: Daily from inclusion till 8 days postoperatively
Area Under the Curve (AUC) for Data on Sleepiness (KSS) - Long-term Postoperative Period
Time frame: App. 14 days postoperatively till 10 weeks postoperatively
Area Under the Curve (AUC) for VAS Data on Fatigue - Immediate Postoperative Period
Time frame: Daily from inclusion till 8 days postoperatively
Area Under the Curve (AUC) for VAS Data on Fatigue - Long-term Postoperative Period
Time frame: App. 14 days postoperatively till 10 weeks postoperatively
Area Under the Curve (AUC) for Data on General Well-being - Immediate Postoperative Period
Time frame: Daily from inclusion till 8 days postoperatively
Area Under the Curve (AUC) for VAS Data on General Well-being - Long-term Postoperative Period
Time frame: App. 14 days postoperatively till 10 weeks postoperatively
Area Under the Curve (AUC) for VAS Data on Pain - Immediate Postoperative Period
Time frame: Daily from inclusion till 8 days postoperatively
Area Under the Curve (AUC) for VAS Data on Pain - Long-term Postoperative Period
Time frame: App. 14 days postoperatively till 10 weeks postoperatively
Area Under the Curve (AUC) for VAS Data on Sleep Quality - Immediate Postoperative Period
Time frame: Daily from inclusion till 8 days postoperatively
Area Under the Curve (AUC) for VAS Data on Sleep Quality - Long-term Postoperative Period
Time frame: App. 14 days postoperatively till 10 weeks postoperatively
Sleep Architecture
Time frame: From inclusion till 14 days postoperatively
HPER3 Genotype
Time frame: At inclusion = day-7
Incidence of Postoperative Cognitive Dysfunction (POCD) App. 2 Weeks Postoperatively.
Time frame: App. 2 weeks postoperatively
Incidence of Postoperative Cognitive Dysfunction (POCD) App. 10 Weeks Postoperatively
Time frame: App. 10 weeks postoperatively
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 25328711Hansen 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Melissa V Hansen, MD principal investigator
Herlev Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Melatonin (N-acetyl-5-methoxytryptamine) in people with Breast Cancer and Depression, run by Melissa Voigt Hansen at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 6 May 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 May 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Major Depression Inventory (MDI)- Depression at One Point in the Study (time frame: 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.). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01355523, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2014.