Randomized Controlled Trial on the Treatment Effects of Melatonin and Light Therapy on Delayed Sleep Phase Syndrome

• Sponsor: University of Bergen (Other)
• Overall Status: Completed
• CT.gov ID: NCT00834886
• Collaborator: (none)
• Enrollment: 40
• Location: 1
• Arms: 4
• Duration (Months): 39
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

In this study the investigators will examine the effects of melatonin and light therapy on delayed sleep phase syndrome in adolescents 16 up to 20 years old. 60 subjects will be randomized into four different groups; melatonin + light therapy (N=15), melatonin + placebo light (N=15), placebo + light therapy (N=15) and placebo + placebo light. This is a double-blinded treatment and the participants will receive this treatment for 2 weeks. Then they will be re-randomized into two groups; full treatment with light therapy + melatonin (N=30) and no treatment (N=30) for 3 months unblinded. The investigators will test the subjects pre-treatment, post 2 week treatment and after 3 months.

Condition or Disease	Intervention/Treatment	Phase
Delayed Sleep Phase Syndrome	Dietary Supplement: Melatonin; Other: Bright light; Other: Placebo red light; Other: Placebo capsule	Phase 4

Detailed Description

Delayed sleep phase syndrome (DSPS) is a circadian rhythm sleep disorder where the sleep-wake rhythm is significantly delayed according to the environmental demands. Hence, the symptoms consist of major difficulties falling asleep and problems awakening in due time and patients often experience work- and school related impairments (The International Classification of Sleep Disorders: Diagnostic and Coding manual, 2005). However, correct diagnosis is often not made and the treatment offered is, accordingly, often inadequate. DSPS normally develops in interplay between dysfunctional habits/behaviour and biological vulnerability.

Bright light therapy and administration of exogenous melatonin comprise the most common interventions. Timed bright light has been shown to effectively phase advance the rhythm (Rosenthal et al., 1990), but no standardized guidelines regarding the duration, intensity or timing of light exposure have been established. Compliance to the treatment is often poor because it involves structuring the daily schedule, which may be hard for the relevant age group. Similarly, administration of melatonin in the evening has been shown to phase advance the rhythm (Lewy et al., 1998; Mundey, Benloucif, Harsanyi, Dubocovich, & Zee, 2005), but a standardized approach for dose, duration and timing is lacking.

It is important to establish effective treatment guidelines for delayed sleep phase syndrome. Large scale studies on the effects of melatonin and bright light treatment in randomized placebo-controlled designs are needed. In a clinical trial we aim to investigate the efficacy of bright light and melatonin treatment using a 4 armed randomized placebo controlled design.

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Delayed Sleep Phase Syndrome in Adolescents and Young Adults. Sleep, Personality, Developmental History, Circadian Rhythm, Daytime Functioning and Treatment
• Study Start Date: Oct 1, 2008
• Actual Primary Completion Date: Jan 1, 2012
• Actual Study Completion Date: Jan 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Combination Bright light 10.000 lux + melatonin 3 mg	Dietary Supplement: Melatonin; Capsules, 3 mg, once every night; Other Names: Nature´s One melatonin, by Asman, Inc. ; Other: Bright light; Bright light therapy 10.000 lux by Miljølys AS
Active Comparator: Melatonin Melatonin 3 mg + placebo red light 400 lux	Dietary Supplement: Melatonin; Capsules, 3 mg, once every night; Other Names: Nature´s One melatonin, by Asman, Inc. ; Other: Placebo red light; Red light 400 lux as placebo light
Active Comparator: Bright light Bright light 10.000 lux + placebo capsule 3 mg rice flour	Other: Bright light; Bright light therapy 10.000 lux by Miljølys AS; Other: Placebo capsule; Capsules containing 3 mng rice flour, once every night
Placebo Comparator: Placebo Placebo Red light 400 lux + placebo capsule 3 mg rice flour	Other: Placebo red light; Red light 400 lux as placebo light; Other: Placebo capsule; Capsules containing 3 mng rice flour, once every night

Outcome Measures

Primary Outcome Measures

1. To Investigate the Efficacy on Rise Time of Bright Light Therapy and Melatonin Treatment Using a 4 Armed Placebo Controlled Design. Main Outcome Measures: Sleep Log, Actigraphy and Psychological Tests. [1 day after two-week treatment ends]

   Sleep diary, rise time (when participants rise from bed in the morning, self-report) before and after a randomized controlled 4 armed treatment study including a follow-up 3 months later. Midnight is 0000; in the outcome measure table the value is given in minutes after midnight. i.e. 530 equals 08:50 in the morning.

2. To Investigate the Efficacy on Subjective Sleepiness of Bright Light Therapy and Melatonin Treatment Using a 4 Armed Placebo Controlled Design. Main Outcome Measures: Sleep Log, Actigraphy and Psychological Tests. [1 day after 2-week treatment ended]

   Subjective sleepiness; Karolinska sleepiness scale (KSS). The KSS is a scale in which the subjects rate their concurrent sleepiness level. The scale is verbally anchored with steps ranging from 1 ("very alert") to 9 ("very sleepy, fighting sleep, effort to stay awake").

3. To Investigate the Efficacy on Sleep Onsel Latency of Bright Light Therapy and Melatonin Treatment Using a 4 Armed Placebo Controlled Design. Main Outcome Measures: Sleep Log, Actigraphy and Psychological Tests. [1 day after 2-week treatment ended]

   Actigraphy, sleep onset latency (SOL). An actigraph is a wrist-worn movement sensor that objectively record motor activity. Participants used an event button to mark bed time and rise time. The actiwatch is waterproof and participants were instructed not to take it off at any time during the data collection peroid.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years to 25 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 16-25 years old

• lives in the Bergen area

• has Delayed Sleep Phase Disorder

Exclusion Criteria:

• pregnant or nursing women

• other sleep disorders (i.e. sleep apnoea or PLMS)

• moderate to serious psychiatric disease

• use of psychopharmacological medicines

• in psychotherapeutic treatment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Bergen	Bergen		Norway	5020

Sponsors and Collaborators

• University of Bergen

Investigators

• Principal Investigator: Bjørn Bjorvatn, MD., PhD, University of Bergen

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bjorn Bjorvatn, Professor, MD, PhD, University of Bergen
• ClinicalTrials.gov Identifier: NCT00834886
• Other Study ID Numbers: 00834886
• First Posted: Feb 3, 2009
• Last Update Posted: Mar 14, 2016
• Last Verified: Mar 1, 2016

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Sleep Disorders, Circadian Rhythm; Syndrome; Melatonin

Study Results

Participant Flow

Arm/Group Title	Combination	Melatonin	Bright Light	Placebo
Arm/Group Description	Melatonin: Capsules, 3 mg, once every night Light therapy: Light therapy 10.000 lux by Miljølys AS	Melatonin: Capsules, 3 mg, once every night placebo light therapy: Placebo light	Placebo melatonin: Capsule 3 mg, rice flour Light therapy: Light therapy 10.000 lux by Miljølys AS	Placebo melatonin + placebo light therapy Placebo melatonin: Capsule 3 mg, rice flour placebo light therapy: Placebo light
Period Title: Overall Study
STARTED	10	10	10	10
COMPLETED	10	9	9	10
NOT COMPLETED	0	1	1	0

Baseline Characteristics

Arm/Group Title	Melatonin and Light Therapy	Melatonin and Placebo Light	Placebo Melatonin and Light Therapy	Placebo Melatonin and Placebo Light	Total
Arm/Group Description	Melatonin: Capsules, 3 mg, once every night Light therapy: Light therapy 10.000 lux by Miljølys AS	Melatonin: Capsules, 3 mg, once every night placebo light therapy: Placebo light	Placebo melatonin: Capsule 3 mg, rice flour Light therapy: Light therapy 10.000 lux by Miljølys AS	Placebo melatonin + placebo light therapy Placebo melatonin: Capsule 3 mg, rice flour placebo light therapy: Placebo light	Total of all reporting groups
Overall Participants	10	10	10	10	40
Age, Customized (years) [Mean (Standard Deviation) ]
Age	20.3 (3.3)	21.2 (2.7)	20.7 (3.4)	20.8 (3.4)	20.7 (3.1)
Sex: Female, Male (Count of Participants)
Female	8 80%	5 50%	8 80%	7 70%	28 70%
Male	2 20%	5 50%	2 20%	3 30%	12 30%
Region of Enrollment (participants) [Number]
Norway	10 100%	10 100%	10 100%	10 100%	40 100%

Outcome Measures

1. Primary Outcome

Title	To Investigate the Efficacy on Rise Time of Bright Light Therapy and Melatonin Treatment Using a 4 Armed Placebo Controlled Design. Main Outcome Measures: Sleep Log, Actigraphy and Psychological Tests.
Description	Sleep diary, rise time (when participants rise from bed in the morning, self-report) before and after a randomized controlled 4 armed treatment study including a follow-up 3 months later. Midnight is 0000; in the outcome measure table the value is given in minutes after midnight. i.e. 530 equals 08:50 in the morning.
Time Frame	1 day after two-week treatment ends

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Combination	Melatonin	Bright Light	Placebo
Arm/Group Description	Bright light + melatonin Melatonin: Capsules, 3 mg, once every night Light therapy: Light therapy 10.000 lux by Miljølys AS	Melatonin + placebo light Melatonin: Capsules, 3 mg, once every night placebo light therapy: Placebo light	Bright light + placebo capsule Placebo melatonin: Capsule 3 mg, rice flour Light therapy: Light therapy 10.000 lux by Miljølys AS	Placebo capsule + placebo light Placebo melatonin: Capsule 3 mg, rice flour placebo light therapy: Placebo light
Measure Participants	10	10	10	10
Mean (Standard Deviation) [Minutes]	530 (121)	506 (98)	520 (148)	543 (163)

2. Primary Outcome

Title	To Investigate the Efficacy on Subjective Sleepiness of Bright Light Therapy and Melatonin Treatment Using a 4 Armed Placebo Controlled Design. Main Outcome Measures: Sleep Log, Actigraphy and Psychological Tests.
Description	Subjective sleepiness; Karolinska sleepiness scale (KSS). The KSS is a scale in which the subjects rate their concurrent sleepiness level. The scale is verbally anchored with steps ranging from 1 ("very alert") to 9 ("very sleepy, fighting sleep, effort to stay awake").
Time Frame	1 day after 2-week treatment ended

Outcome Measure Data

Analysis Population Description

All participants in the four arms

Arm/Group Title	Combination	Melatonin	Bright Light	Placebo
Arm/Group Description	Bright light + melatonin Melatonin: Capsules, 3 mg, once every night Light therapy: Light therapy 10.000 lux by Miljølys AS	Melatonin + placebo light Melatonin: Capsules, 3 mg, once every night placebo light therapy: Placebo light	Bright light + placebo capsule Placebo melatonin: Capsule 3 mg, rice flour Light therapy: Light therapy 10.000 lux by Miljølys AS	Placebo capsule + placebo light Placebo melatonin: Capsule 3 mg, rice flour placebo light therapy: Placebo light
Measure Participants	10	10	10	10
Mean (Standard Deviation) [units on a scale]	6.0 (1.6)	5.9 (1.3)	6.3 (1.8)	6.5 (1.5)

3. Primary Outcome

Title	To Investigate the Efficacy on Sleep Onsel Latency of Bright Light Therapy and Melatonin Treatment Using a 4 Armed Placebo Controlled Design. Main Outcome Measures: Sleep Log, Actigraphy and Psychological Tests.
Description	Actigraphy, sleep onset latency (SOL). An actigraph is a wrist-worn movement sensor that objectively record motor activity. Participants used an event button to mark bed time and rise time. The actiwatch is waterproof and participants were instructed not to take it off at any time during the data collection peroid.
Time Frame	1 day after 2-week treatment ended

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Combination	Melatonin	Bright Light	Placebo
Arm/Group Description	Bright light + melatonin Melatonin: Capsules, 3 mg, once every night Light therapy: Light therapy 10.000 lux by Miljølys AS	Melatonin + placebo light Melatonin: Capsules, 3 mg, once every night placebo light therapy: Placebo light	Bright light + placebo capsule Placebo melatonin: Capsule 3 mg, rice flour Light therapy: Light therapy 10.000 lux by Miljølys AS	Placebo capsule + placebo light Placebo melatonin: Capsule 3 mg, rice flour placebo light therapy: Placebo light
Measure Participants	10	10	10	10
Mean (Standard Deviation) [Minutes]	11 (8)	21 (19)	15 (10)	24 (11)

Adverse Events

Arm/Group Title	Combination		Melatonin		Bright Light		Placebo
Arm/Group Description	Melatonin: Capsules, 3 mg, once every night Light therapy: Light therapy 10.000 lux by Miljølys AS		Melatonin: Capsules, 3 mg, once every night placebo light therapy: Placebo light		Placebo melatonin: Capsule 3 mg, rice flour Light therapy: Light therapy 10.000 lux by Miljølys AS		Placebo melatonin + placebo light therapy Placebo melatonin: Capsule 3 mg, rice flour placebo light therapy: Placebo light
All Cause Mortality
	Combination		Melatonin		Bright Light		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Combination		Melatonin		Bright Light		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	Combination		Melatonin		Bright Light		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/10 (40%)		4/10 (40%)		3/10 (30%)		4/10 (40%)
Eye disorders
Discomfort in eyes	2/10 (20%)		1/10 (10%)		1/10 (10%)		1/10 (10%)
Gastrointestinal disorders
Nausea	0/10 (0%)		2/10 (20%)		0/10 (0%)		0/10 (0%)
Nervous system disorders
Headache	2/10 (20%)		1/10 (10%)		1/10 (10%)		2/10 (20%)
Skin and subcutaneous tissue disorders
Skin irritation	0/10 (0%)		0/10 (0%)		1/10 (10%)		1/10 (10%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.