Functional Melatonin Replacement for Sleep Disruptions in Individuals With Tetraplegia

• Sponsor: US Department of Veterans Affairs (U.S. Fed)
• Overall Status: Completed
• CT.gov ID: NCT00507546
• Collaborator: Stanford University (Other), Takeda (Industry)
• Enrollment: 12
• Location: 1
• Arms: 2
• Duration (Months): 48
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if replacing melatonin function with a melatonin agonist (ramelteon) in individuals that lack endogenous melatonin production (tetraplegia) helps to alleviate self-reported sleep disruption.

Condition or Disease	Intervention/Treatment	Phase
Insomnia; Spinal Cord Injury; Tetraplegia; Sleep Disorders	Drug: Ramelteon; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Melatonin Replacement for Treatment of Sleep Disruption
• Study Start Date: Jul 1, 2007
• Actual Primary Completion Date: Dec 1, 2010
• Actual Study Completion Date: Jul 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ramelteon then placebo 8 mg nightly ramelteon for three weeks, followed by two weeks of nightly placebo (washout), then three weeks of nightly placebo (cross-over)	Drug: Ramelteon; 8 mg nightly; Other Names: Rozerem
Experimental: Placebo then ramelteon placebo nightly for three weeks, followed by two weeks of nightly placebo (washout), then three weeks of 8 mg nightly ramelteon (cross-over)	Drug: Placebo; Nightly 8mg of placebo (same appearance as ramelteon)

Outcome Measures

Primary Outcome Measures

1. Amount of Wakefulness After Sleep Onset (WASO) [10 weeks]

   Measured as the median of the average WASO of the three weeks of either placebo or ramelteon treatment

Secondary Outcome Measures

1. Change in Subjective Morning Alertness [10 weeks]

   Measured as the median of the average morning alertness (measured from 1-7 on the Stanford Sleepiness Scale, a Likert-like scale in which higher values are lower alertness) of the three weeks of either placebo or ramelteon treatment

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Age 18 years or older, male or female veterans of any racial or ethnic group

• Neurologically complete (Frankel A or B) damage to the lower (C4-C8) cervical spinal cord

• Absence of melatonin production

• Time since SCI is greater than 6 months [no cases of acute spinal cord injury]

• Subjective complaint of sleep disruption

Exclusion Criteria:

• Current use of fluvoxamine (Luvox , antidepressant), rifampin (antimycobacterial), ketoconazole (Nizoral , antifungal), or fluconazole (Diflucan , antifungal) [these interact with the same liver enzyme that is the primary metabolizer of ramelteon]; use of sleep medications is okay

• Hepatic dysfunction

• Concomitant use of over-the-counter melatonin

• Pregnancy or breast feeding

• Currently or have within the past six months met DSM-IV (Diagnosis and Statistical Manual IV) criteria for drug or alcohol abuse or dependence or AUDIT score >19

• Acute illness or unstable chronic illness. Use of continuous positive airway pressure (CPAP) for treatment of sleep apnea is acceptable.

• No travel across three or more time zones within three weeks or during the protocol

• Illiterate or unable to read or write English or are judged by the investigator to be unable or unlikely to follow the study protocol

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	VA Palo Alto Health Care System	Palo Alto	California	United States	94304-1290

Sponsors and Collaborators

• US Department of Veterans Affairs
• Stanford University
• Takeda

Investigators

• Principal Investigator: Jamie M. Zeitzer, PhD, VA Palo Alto Health Care System

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: US Department of Veterans Affairs
• ClinicalTrials.gov Identifier: NCT00507546
• Other Study ID Numbers: B6010-R; 06-038R
• First Posted: Jul 26, 2007
• Last Update Posted: May 22, 2014
• Last Verified: Apr 1, 2014

• Keywords provided by US Department of Veterans Affairs: sleep; melatonin; spinal cord injury; insomnia; tetraplegia
• Additional relevant MeSH terms: Spinal Cord Injuries; Sleep Initiation and Maintenance Disorders; Sleep Wake Disorders; Quadriplegia

Study Results

Participant Flow

Recruitment Details	Subjects recruited from community
Pre-assignment Detail	Subjects excluded if baseline measure detected the presence of melatonin metabolite in their urine.

Arm/Group Title	Arm 1	Arm 2
Arm/Group Description	Ramelteon then placebo Ramelteon : 8 mg nightly	Placebo then ramelteon Placebo : Nightly 8mg of placebo (same appearance as ramelteon)
Period Title: Overall Study
STARTED	4	4
COMPLETED	2	3
NOT COMPLETED	2	1

Baseline Characteristics

Arm/Group Title	Arm 1	Arm 2	Total
Arm/Group Description	Ramelteon then placebo Ramelteon : 8 mg nightly	Placebo then ramelteon Placebo : Nightly 8mg of placebo (same appearance as ramelteon)	Total of all reporting groups
Overall Participants	4	4	8
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	4 100%	4 100%	8 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.25 (9.74)	55.5 (15.5)	53 (12)
Sex: Female, Male (Count of Participants)
Female	0 0%	1 25%	1 12.5%
Male	4 100%	3 75%	7 87.5%
Region of Enrollment (participants) [Number]
United States	4 100%	4 100%	8 100%

Outcome Measures

1. Primary Outcome

Title	Amount of Wakefulness After Sleep Onset (WASO)
Description	Measured as the median of the average WASO of the three weeks of either placebo or ramelteon treatment
Time Frame	10 weeks

Outcome Measure Data

Analysis Population Description

All participants who completed the entire protocol.

Arm/Group Title	Ramelteon	Placebo
Arm/Group Description	Ramelteon then placebo Ramelteon : 8 mg nightly	Placebo then ramelteon Placebo : Nightly 8mg of placebo (same appearance as ramelteon)
Measure Participants	3	2
Median (Full Range) [Minutes]	72.3	76.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.70
	Comments
	Method	Friedman
	Comments

2. Secondary Outcome

Title	Change in Subjective Morning Alertness
Description	Measured as the median of the average morning alertness (measured from 1-7 on the Stanford Sleepiness Scale, a Likert-like scale in which higher values are lower alertness) of the three weeks of either placebo or ramelteon treatment
Time Frame	10 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1	Arm 2
Arm/Group Description	Ramelteon then placebo Ramelteon : 8 mg nightly	Placebo then ramelteon Placebo : Nightly 8mg of placebo (same appearance as ramelteon)
Measure Participants	3	2
Median (Full Range) [units on a scale]	2.86	3.14

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.35
	Comments
	Method	Friedman
	Comments

Adverse Events

Arm/Group Title	Arm 1		Arm 2
Arm/Group Description	Ramelteon then placebo Ramelteon : 8 mg nightly		Placebo then ramelteon Placebo : Nightly 8mg of placebo (same appearance as ramelteon)
All Cause Mortality
	Arm 1		Arm 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm 1		Arm 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/4 (0%)
Other (Not Including Serious) Adverse Events
	Arm 1		Arm 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/4 (0%)

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.