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| Name | Class |
|---|---|
| I.M Daehnfeldt Foundation | UNKNOWN |
| Danish Cancer Society | OTHER |
| Aase and Ejnar Danielsens Foundation | OTHER |
| Beckett Foundation |
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BACKGROUND:
Patients with advanced cancer often suffer from fatigue and other symptoms and problems such as insomnia, appetite loss and pain. Problems that may have great consequences for their quality of life. Several studies suggest that a supplement of the hormone melatonin (MLT) may have a beneficial effect on these symptoms/problems. This needs further investigation.
AIM:
To investigate if a supplement of melatonin have an effect on a) fatigue (the primary outcome of the trial), b) the symptoms insomnia, appetite loss, depression and pain, and c) overall quality of life.
METHODS AND PATIENTS:
The trial takes place in the Department of Palliative Medicine, Bispebjerg Hospital, and 50 patients will participate. The participants have to be 18 years or above, have advanced cancer, and suffer from quite a bit or very much fatigue.
The study consists of two parts. In part I it is investigated if melatonin has a better effect than placebo on the outcomes mentioned above. This part is a consecutive, prospective, double blinded, randomized (MLT vs. placebo), cross-over study where the patients serve as their own control. In part II the effect of melatonin over time is investigated. Part II is a consecutive, prospective, open-label study.
The outcomes are assessed with weekly questionnaires (MFI-20 and EORTC QLQ-C15PAL) and a few daily diary questions.
Melatonin has been used in several studies, and the general conclusion is that it is a safe substance with few adverse drug reactions.
PERSPECTIVES:
If melatonin has the potential to alleviate fatigue and other symptoms in patients with advanced cancer and enhance the quality of life of these patients, this will be of benefit to many future patients. Trials such as this are important both nationally and internationally to develop an evidence-based palliative medicine.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Melatonin | Experimental | 20 mg |
|
| Placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Melatonin | Drug | 20 mg melatonin orally every evening about 1 hour before bedtime for one week. After having participated in the cross-over part of the trial (one week of melatonin followed by one week of placebo, or the other way around), the participant may receive melatonin for 6 weeks. |
| Measure | Description | Time Frame |
|---|---|---|
| Fatigue as Measured by the Physical Fatigue Scale in the The Multidimensional Fatigue Inventory (MFI) (Smets EM, Garssen B, Bonke B, et al., J Psychosom Res 39:315-325, 1995) | Primary outcome: Change from baseline to week one in intervention group minus change from baseline to week one in control group. Because it was a cross-over trial this was calculated the following way: Outcomes for arm 1 (melatonin then placebo) were calculated as the difference in mean change scores between week 1 and week 2 (scores for day 7 to day 1-scores for day 17 to day 10). Outcomes for arm 2 (placebo then melatonin) were calculated as the difference in mean change scores between week 2 and week 1 (scores for day 17 to day 10-scores for day 7 to day 1). The physical fatigue scale conists of four item each ranging from one to five. The four item were summed and the scae was converted to 0 to 100, where 100 indicated maximum fatigue. | One week |
| Measure | Description | Time Frame |
|---|---|---|
| Insomnia Measured by the Insomnia Item in the Questionnaire EORTC QLQ-C15-PAL | Primary outcome: Change from baseline to week one in intervention group minus change from baseline to week one in control group. Because it was a cross-over trial this was calculated the following way: Outcomes for arm 1 (melatonin then placebo) were calculated as the difference in mean change scores between week 1 and week 2 (scores for day 7 to day 1-scores for day 17 to day 10). Outcomes for arm 2 (placebo then melatonin) were calculated as the difference in mean change scores between week 2 and week 1 (scores for day 17 to day 10-scores for day 7 to day 1). Insomnia was converted to a 0 til 100 scale according to the scoring manual for EORTC QLQ C15-PAL where 100 indicated maximum insomnia. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Lise Pedersen, MD, DMSc. | Department of Palliative Medicine, Bispebjerg Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Palliative Medicine, Bispebjerg Hospital | Copenhagen | 2400 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26178160 | Result | Lund Rasmussen C, Klee Olsen M, Thit Johnsen A, Petersen MA, Lindholm H, Andersen L, Villadsen B, Groenvold M, Pedersen L. Effects of melatonin on physical fatigue and other symptoms in patients with advanced cancer receiving palliative care: A double-blind placebo-controlled crossover trial. Cancer. 2015 Oct 15;121(20):3727-36. doi: 10.1002/cncr.29563. Epub 2015 Jul 15. |
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72 patients were randomised in the study. 50 patients completed the first part of the stud, only 44 patients were complete compliers (having taking their melatonin and placebo for at least five days each week and having answered the questionnaires at all times). The primary analysis is of the 44 complete compliers.
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| ID | Title | Description |
|---|---|---|
| FG000 | Part 1: Melatonin, Then Placebo | First one week Melatonin: 20 mg melatonin orally every evening about 1 hour before bedtime for one week. Then one week Placebo: Placebo tablet orally every evening about one hour before bedtime for one week. |
| FG001 | Part 1: Placebo, Then Melatonin | First one week Placebo: Placebo tablet orally every evening about one hour before bedtime for one week. Then one week Melatonin: 20 mg melatonin orally every evening about 1 hour before bedtime for one week. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1 |
|
| |||||||||||||||||||||
| Part 2 |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Melatonin, Then Placebo | Melatonin then placebo: 20 mg melatonin orally every evening about 1 hour before bedtime for one week. Then 1 week placebo. |
| BG001 | Placebo. Then Melatonin |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Fatigue as Measured by the Physical Fatigue Scale in the The Multidimensional Fatigue Inventory (MFI) (Smets EM, Garssen B, Bonke B, et al., J Psychosom Res 39:315-325, 1995) | Primary outcome: Change from baseline to week one in intervention group minus change from baseline to week one in control group. Because it was a cross-over trial this was calculated the following way: Outcomes for arm 1 (melatonin then placebo) were calculated as the difference in mean change scores between week 1 and week 2 (scores for day 7 to day 1-scores for day 17 to day 10). Outcomes for arm 2 (placebo then melatonin) were calculated as the difference in mean change scores between week 2 and week 1 (scores for day 17 to day 10-scores for day 7 to day 1). The physical fatigue scale conists of four item each ranging from one to five. The four item were summed and the scae was converted to 0 to 100, where 100 indicated maximum fatigue. | The primary analysis was a per protocol analysis including only complete compliers, defined as those patients who had consumed at least 5 capsules per week for the 2 weeks in part 1 and who had answered the MFI-20 on days 1, 7, 10, and 17. | Posted | Mean | Standard Deviation | units on a scale | One week |
SUSARS were registered for part 1 (two weeks plus washout phase) and part 2 (six weeks)
Only SUSAR (suspected unexpected serious adverse reactions) are reported because the study population was patients in palliative care with many potential adverse events
Data are not presented per intervention and since there were '0' SUSAR in both groups this does not matter.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Melatonin Then Placebo | Melatonin 20 mg melatonin orally every evening about 1 hour before bedtime for one week. Then placebo for one week. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Lise Pedersen | Bispebjerg Hospital | 004535312305 | lise.pedersen.01@regionh.dk |
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| ID | Term |
|---|---|
| D009369 | Neoplasms |
| D005221 | Fatigue |
| ID | Term |
|---|---|
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D008550 | Melatonin |
| ID | Term |
|---|---|
| D014363 | Tryptamines |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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| OTHER |
| The Andersen-Isted Foundation | UNKNOWN |
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|
| Placebo | Drug | Placebo tablet orally every evening about one hour before bedtime for one week. After having participated in the cross-over part of the trial (one week of placebo followed by one week of melatonin, or the other way around), the participant may receive melatonin for 6 weeks. |
|
| One week |
| Emotional Function as Measured by the Questionnaire EORTC QLQ-C15-PAL (Groenvold M, Petersen MA, Aaronson NK, et al, Eur J Cancer 42:55-64, 2006) | Change from baseline to week one in intervention group minus change from baseline to week one in control group. Because it was a cross-over trial this was calculated the following way: Outcomes for arm 1 (melatonin then placebo) were calculated as the difference in mean change scores between week 1 and week 2 (scores for day 7 to day 1-scores for day 17 to day 10). Outcomes for arm 2 (placebo then melatonin) were calculated as the difference in mean change scores between week 2 and week 1 (scores for day 17 to day 10-scores for day 7 to day 1). Emotional function was converted to a 0 til 100 scale according to the scoring manual for EORTC QLQ C15-PAL where 100 indicated the best possible emotional function. Note outcome reported for complete compliers | One week |
| Pain as Measured by the Questionnaire EORTC QLQ-C15-PAL (Groenvold M, Petersen MA, Aaronson NK, et al, Eur J Cancer 42:55-64, 2006) | Change from baseline to week one in intervention group minus change from baseline to week one in control group. Because it was a cross-over trial this was calculated the following way: Outcomes for arm 1 (melatonin then placebo) were calculated as the difference in mean change scores between week 1 and week 2 (scores for day 7 to day 1-scores for day 17 to day 10). Outcomes for arm 2 (placebo then melatonin) were calculated as the difference in mean change scores between week 2 and week 1 (scores for day 17 to day 10-scores for day 7 to day 1). Pain was converted to a 0 til 100 scale according to the scoring manual for EORTC QLQ C15-PAL where 100 indicated maximum pain. Note outcome reported for complete compliers | One week |
| Quality of Life as Measured by the Questionnaire EORTC QLQ-C15-PAL (Groenvold M, Petersen MA, Aaronson NK, et al, Eur J Cancer 42:55-64, 2006) | Change from baseline to week one in intervention group minus change from baseline to week one in control group. Because it was a cross-over trial this was calculated the following way: Outcomes for arm 1 (melatonin then placebo) were calculated as the difference in mean change scores between week 1 and week 2 (scores for day 7 to day 1-scores for day 17 to day 10). Outcomes for arm 2 (placebo then melatonin) were calculated as the difference in mean change scores between week 2 and week 1 (scores for day 17 to day 10-scores for day 7 to day 1). Quality of Life was converted to a 0 til 100 scale according to the scoring manual for EORTC QLQ C15-PAL where 100 indicated best possible quality of life. Note outcome reported for complete compliers | One week |
| Appetite Loss as Measured by the Questionnaire EORTC QLQ-C15-PAL (Groenvold M, Petersen MA, Aaronson NK, et al, Eur J Cancer 42:55-64, 2006) | Change from baseline to week one in intervention group minus change from baseline to week one in control group. Because it was a cross-over trial this was calculated the following way: Outcomes for arm 1 (melatonin then placebo) were calculated as the difference in mean change scores between week 1 and week 2 (scores for day 7 to day 1-scores for day 17 to day 10). Outcomes for arm 2 (placebo then melatonin) were calculated as the difference in mean change scores between week 2 and week 1 (scores for day 17 to day 10-scores for day 7 to day 1). Appetite loss was converted to a 0 til 100 scale according to the scoring manual for EORTC QLQ C15-PAL where 100 indicated maximum appetite loss (worst possible). Note outcome reported for complete compliers | One week |
| General Fatigue Measured by the The Multidimensional Fatigue Inventory (MFI) | Change from baseline to week one in intervention group minus change from baseline to week one in control group. Because it was a cross-over trial this was calculated the following way: Outcomes for arm 1 (melatonin then placebo) were calculated as the difference in mean change scores between week 1 and week 2 (scores for day 7 to day 1-scores for day 17 to day 10). Outcomes for arm 2 (placebo then melatonin) were calculated as the difference in mean change scores between week 2 and week 1 (scores for day 17 to day 10-scores for day 7 to day 1). The general fatigue scale that consits of four items was converted to a 0 til 100 scale where 100 indicated maximum (worst possible) fatigue. Note outcome reported for complete compliers | One week |
| NOT COMPLETED |
|
Placebo then melatonin: Placebo tablet orally every evening about one hour before bedtime for one week. Then one week melatonin 20 mg orally.
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| ID | Title | Description |
|---|
| OG000 | Melatonin Then Placebo | 20 mg Melatonin orally every evening about 1 hour before bedtime for one week. Then Placebo tablet orally every evening about one hour before bedtime for one week. Three days wash out in between. |
| OG001 | Placebo Then Melatonin | Placebo tablet orally every evening about one hour before bedtime for one week. Then melatonin 20 mg melatonin orally every evening about 1 hour before bedtime for one week. Three days wash out in between. |
|
|
| Secondary | Insomnia Measured by the Insomnia Item in the Questionnaire EORTC QLQ-C15-PAL | Primary outcome: Change from baseline to week one in intervention group minus change from baseline to week one in control group. Because it was a cross-over trial this was calculated the following way: Outcomes for arm 1 (melatonin then placebo) were calculated as the difference in mean change scores between week 1 and week 2 (scores for day 7 to day 1-scores for day 17 to day 10). Outcomes for arm 2 (placebo then melatonin) were calculated as the difference in mean change scores between week 2 and week 1 (scores for day 17 to day 10-scores for day 7 to day 1). Insomnia was converted to a 0 til 100 scale according to the scoring manual for EORTC QLQ C15-PAL where 100 indicated maximum insomnia. | Complete compliers | Posted | Mean | Standard Deviation | units on a scale | One week |
|
|
|
| Secondary | Emotional Function as Measured by the Questionnaire EORTC QLQ-C15-PAL (Groenvold M, Petersen MA, Aaronson NK, et al, Eur J Cancer 42:55-64, 2006) | Change from baseline to week one in intervention group minus change from baseline to week one in control group. Because it was a cross-over trial this was calculated the following way: Outcomes for arm 1 (melatonin then placebo) were calculated as the difference in mean change scores between week 1 and week 2 (scores for day 7 to day 1-scores for day 17 to day 10). Outcomes for arm 2 (placebo then melatonin) were calculated as the difference in mean change scores between week 2 and week 1 (scores for day 17 to day 10-scores for day 7 to day 1). Emotional function was converted to a 0 til 100 scale according to the scoring manual for EORTC QLQ C15-PAL where 100 indicated the best possible emotional function. Note outcome reported for complete compliers | Posted | Mean | Standard Deviation | units on a scale | One week |
|
|
|
| Secondary | Pain as Measured by the Questionnaire EORTC QLQ-C15-PAL (Groenvold M, Petersen MA, Aaronson NK, et al, Eur J Cancer 42:55-64, 2006) | Change from baseline to week one in intervention group minus change from baseline to week one in control group. Because it was a cross-over trial this was calculated the following way: Outcomes for arm 1 (melatonin then placebo) were calculated as the difference in mean change scores between week 1 and week 2 (scores for day 7 to day 1-scores for day 17 to day 10). Outcomes for arm 2 (placebo then melatonin) were calculated as the difference in mean change scores between week 2 and week 1 (scores for day 17 to day 10-scores for day 7 to day 1). Pain was converted to a 0 til 100 scale according to the scoring manual for EORTC QLQ C15-PAL where 100 indicated maximum pain. Note outcome reported for complete compliers | Complete compliers | Posted | Mean | Standard Deviation | units on a scale | One week |
|
|
|
| Secondary | Quality of Life as Measured by the Questionnaire EORTC QLQ-C15-PAL (Groenvold M, Petersen MA, Aaronson NK, et al, Eur J Cancer 42:55-64, 2006) | Change from baseline to week one in intervention group minus change from baseline to week one in control group. Because it was a cross-over trial this was calculated the following way: Outcomes for arm 1 (melatonin then placebo) were calculated as the difference in mean change scores between week 1 and week 2 (scores for day 7 to day 1-scores for day 17 to day 10). Outcomes for arm 2 (placebo then melatonin) were calculated as the difference in mean change scores between week 2 and week 1 (scores for day 17 to day 10-scores for day 7 to day 1). Quality of Life was converted to a 0 til 100 scale according to the scoring manual for EORTC QLQ C15-PAL where 100 indicated best possible quality of life. Note outcome reported for complete compliers | Complete compliers | Posted | Mean | Standard Deviation | units on a scale | One week |
|
|
|
| Secondary | Appetite Loss as Measured by the Questionnaire EORTC QLQ-C15-PAL (Groenvold M, Petersen MA, Aaronson NK, et al, Eur J Cancer 42:55-64, 2006) | Change from baseline to week one in intervention group minus change from baseline to week one in control group. Because it was a cross-over trial this was calculated the following way: Outcomes for arm 1 (melatonin then placebo) were calculated as the difference in mean change scores between week 1 and week 2 (scores for day 7 to day 1-scores for day 17 to day 10). Outcomes for arm 2 (placebo then melatonin) were calculated as the difference in mean change scores between week 2 and week 1 (scores for day 17 to day 10-scores for day 7 to day 1). Appetite loss was converted to a 0 til 100 scale according to the scoring manual for EORTC QLQ C15-PAL where 100 indicated maximum appetite loss (worst possible). Note outcome reported for complete compliers | Complete compliers | Posted | Mean | Standard Deviation | units on a scale | One week |
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|
|
| Secondary | General Fatigue Measured by the The Multidimensional Fatigue Inventory (MFI) | Change from baseline to week one in intervention group minus change from baseline to week one in control group. Because it was a cross-over trial this was calculated the following way: Outcomes for arm 1 (melatonin then placebo) were calculated as the difference in mean change scores between week 1 and week 2 (scores for day 7 to day 1-scores for day 17 to day 10). Outcomes for arm 2 (placebo then melatonin) were calculated as the difference in mean change scores between week 2 and week 1 (scores for day 17 to day 10-scores for day 7 to day 1). The general fatigue scale that consits of four items was converted to a 0 til 100 scale where 100 indicated maximum (worst possible) fatigue. Note outcome reported for complete compliers | Posted | Mean | Standard Deviation | units on a scale | One week |
|
|
|
| 0 |
| 34 |
| 0 |
| 34 |
| EG001 | Placebo Then Melatonin | Placebo tablet orally every evening about one hour before bedtime for one week. Then melatonin 20 mg. for one week. | 0 | 38 | 0 | 38 |
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| D006571 | Heterocyclic Compounds |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |