Trial Outcomes & Findings for Melatonin for Fatigue and Other Symptoms in Patients With Advanced Cancer (NCT NCT00925899)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

72 participants

Primary outcome timeframe

One week

Results posted on

2017-04-20

Participant Flow

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.

Participant milestones

Participant milestones
Measure	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.	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.
Part 1 STARTED	34	38
Part 1 COMPLETED	23	27
Part 1 NOT COMPLETED	11	11
Part 2 STARTED	15	21
Part 2 COMPLETED	9	9
Part 2 NOT COMPLETED	6	12

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.
Part 1 Death	1	2
Part 1 Withdrawal by Subject	10	9

Baseline Characteristics

Melatonin for Fatigue and Other Symptoms in Patients With Advanced Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Melatonin, Then Placebo n=34 Participants Melatonin then placebo: 20 mg melatonin orally every evening about 1 hour before bedtime for one week. Then 1 week placebo.	Placebo. Then Melatonin n=38 Participants Placebo then melatonin: Placebo tablet orally every evening about one hour before bedtime for one week. Then one week melatonin 20 mg orally.	Total n=72 Participants Total of all reporting groups
Age, Continuous	65 years n=5 Participants	62 years n=7 Participants	63 years n=5 Participants
Sex: Female, Male Female	24 Participants n=5 Participants	25 Participants n=7 Participants	49 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	13 Participants n=7 Participants	23 Participants n=5 Participants

PRIMARY outcome

Timeframe: One week

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Melatonin Then Placebo n=21 Participants 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.	Placebo Then Melatonin n=23 Participants 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.
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)	-1.1 units on a scale Standard Deviation 15.9	-3.9 units on a scale Standard Deviation 18.1

SECONDARY outcome

Timeframe: One week

Population: Complete compliers

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.

Outcome measures

Outcome measures
Measure	Melatonin Then Placebo n=21 Participants 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.	Placebo Then Melatonin n=23 Participants 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.
Insomnia Measured by the Insomnia Item in the Questionnaire EORTC QLQ-C15-PAL	-9.9 units on a scale Standard Deviation 23.4	-4.6 units on a scale Standard Deviation 30.9

SECONDARY outcome

Timeframe: One week

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

Outcome measures

Outcome measures
Measure	Melatonin Then Placebo n=21 Participants 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.	Placebo Then Melatonin n=23 Participants 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.
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)	-0.6 units on a scale Standard Deviation 23.5	3.3 units on a scale Standard Deviation 18.5

SECONDARY outcome

Timeframe: One week

Population: Complete compliers

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

Outcome measures

Outcome measures
Measure	Melatonin Then Placebo n=21 Participants 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.	Placebo Then Melatonin n=23 Participants 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.
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)	0.8 units on a scale Standard Deviation 19.3	1.9 units on a scale Standard Deviation 22.2

SECONDARY outcome

Timeframe: One week

Population: Complete compliers

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

Outcome measures

Outcome measures
Measure	Melatonin Then Placebo n=21 Participants 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.	Placebo Then Melatonin n=23 Participants 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.
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)	-0.8 units on a scale Standard Deviation 13.6	-3.2 units on a scale Standard Deviation 19.2

SECONDARY outcome

Timeframe: One week

Population: Complete compliers

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

Outcome measures

Outcome measures
Measure	Melatonin Then Placebo n=21 Participants 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.	Placebo Then Melatonin n=23 Participants 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.
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)	-0.8 units on a scale Standard Deviation 25.4	-3.2 units on a scale Standard Deviation 21.6

SECONDARY outcome

Timeframe: One week

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

Outcome measures

Outcome measures
Measure	Melatonin Then Placebo n=21 Participants 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.	Placebo Then Melatonin n=23 Participants 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.
General Fatigue Measured by the The Multidimensional Fatigue Inventory (MFI)	-3.2 units on a scale Standard Deviation 18.6	-2.1 units on a scale Standard Deviation 24.8

Adverse Events

Melatonin Then Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo Then Melatonin

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Lise Pedersen

Bispebjerg Hospital

Phone: 004535312305

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place