Working… Menu

Efficacy and Safety of Ramelteon in Subjects With Mild to Moderate Alzheimer's Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00325728
Recruitment Status : Completed
First Posted : May 15, 2006
Last Update Posted : August 14, 2017
Information provided by (Responsible Party):

Brief Summary:
The purpose of this study is to determine the efficacy of ramelteon, once daily (QD), in subjects with mild to moderate Alzheimer's Disease and sleep disturbance

Condition or disease Intervention/treatment Phase
Chronic Insomnia Drug: Ramelteon Drug: Placebo Phase 2

Detailed Description:

Epidemiological data for 2005 show that an estimated 4.2 million people in the US suffer from Alzheimer's disease, often necessitating caregiver assistance, which can in many cases progress to institutionalization. Subjects with Alzheimer's disease dementia frequently experience disturbed sleep patterns characterized by insufficient nocturnal sleep and excessive daytime napping, which has been associated with both cognitive and behavioral pathology such as impaired daytime functioning, agitation, and nocturnal wandering.

Although the causality of sleep disturbances in Alzheimer's disease remains unclear; some research suggests that the fragmented sleep and associated behavioral disturbances could be related to the degeneration of the serotonergic and noradrenergic innervation of suprachiasmatic nucleus andsubsequent disruption in melatonin secretion patterns. Additionally, research suggests that melatonin levels are decreased in patients with Alzheimer's disease

In the United States, ramelteon is marketed for the treatment of insomnia characterized by difficulty with sleep onset and is under global development for the treatment of transient, chronic insomnia and circadian rhythm sleep disorders. It is believed that ramelteon works by binding melatonin to MT1/MT2 receptors in the suprachiasmatic nucleus which inhibits firing of specific neurons, which is thought to attenuate the alerting signal and allows the homeostatic mechanism to express itself and promote sleep.

Study participation is anticipated to be about 11 weeks (approximately 3 months).

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 74 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-Blind, Randomized, Placebo-Controlled Study of the Efficacy, Safety and Tolerability of 8 Week Treatment of Rozerem 8 mg (QHS) in Sleep Disturbed, Mild to Moderately Severe Alzheimer's Disease Subjects
Actual Study Start Date : March 21, 2006
Actual Primary Completion Date : August 1, 2007
Actual Study Completion Date : August 20, 2007

Resource links provided by the National Library of Medicine

Drug Information available for: Ramelteon

Arm Intervention/treatment
Experimental: Ramelteon 8 mg QD Drug: Ramelteon
Ramelteon 8mg, tablets, orally, once nightly for up to 8 weeks.
Other Names:
  • TAK-375
  • Rozerem

Placebo Comparator: Placebo Drug: Placebo
Ramelteon placebo matching tablets, orally, once nightly for up to 8 weeks.

Primary Outcome Measures :
  1. Mean Nighttime Total Sleep Time as determined by actigraphy. [ Time Frame: Week 1 ]

Secondary Outcome Measures :
  1. Change from Baseline in Nighttime Total Sleep Time [ Time Frame: Weeks 2, 4, 6, and 8 or Final Visit ]
  2. Change from Baseline in Nighttime Wake After Sleep Onset per Actigraphy [ Time Frame: Weeks 2, 4, 6, and 8 or Final Visit ]
  3. Change from Baseline in Nighttime Number Of Awakenings per Actigraphy [ Time Frame: Weeks 2, 4, 6, and 8 or Final Visit ]
  4. Change from Baseline in Daytime Total Sleep Time [ Time Frame: Weeks 2, 4, 6, and 8 or Final Visit ]
  5. Change from Baseline in the ratio of Daytime Total Sleep Time to Nighttime Total Sleep Time. [ Time Frame: Weeks 2, 4, 6, and 8 or Final Visit ]
  6. Change from Baseline in Sleep Efficiency. [ Time Frame: Weeks 2, 4, 6, and 8 or Final Visit ]
  7. Percentage of subjects who experience Increase in Nighttime Total Sleep Time of 30 minutes. [ Time Frame: Weeks 2, 4, 6, and 8 or Final Visit ]
  8. Number of Daytime Naps. [ Time Frame: Weeks 2, 4, 6, and 8 or Final Visit ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   55 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria

  • Clinical diagnosis of dementia of the Alzheimer's type (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Revised) or probable Alzheimer's disease by National Institute of Neurological and Communicative Disorders and Stroke/the Alzheimer's Disease and Related
  • Disorders Association criteria.
  • Female subjects must be post-menopausal.
  • Stable residence with no planned move during the entire investigation period.
  • Residing in the same residence with a responsible spouse, family member, or a professional caregiver who is present during the night who would agree to assume the role of the principal caregiver for the duration of the protocol period.
  • Able to ingest oral medication and participate in all scheduled evaluations.
  • Clinical laboratory evaluations (including clinical chemistry, hematology, and urinalysis) within the reference range as tested by the designated laboratory unless the results are deemed not clinically significant by the investigator or sponsor.
  • Treatment medications for any non-excluded medications or concurrent medical conditions are stable for 30 days prior to the screening visit and medication(s) can in the investigator's judgment, remain stable throughout the duration of the study.
  • Mini-Mental State Examination score of 8 to 28, inclusive.
  • History of greater than or equal to 2 sleep disorder behaviors, occurring at least once weekly over the two weeks before screening.
  • Actigraphy evidence shows a nighttime total sleep time of less than 7 hours per night based on at least 4 out of 7 nights of complete actigraphy data collected over the single-blind, placebo run-in period.
  • Habitual bedtime of between 8 PM and 12 AM.

Exclusion Criteria

  • Non-ambulatory, wheel chair bound or confined to bed and is without a consistent caregiver who is present during the night who could function as the primary caregiver.
  • Caregiver is deemed by the investigator to be unreliable to supervise the wearing of the actigraphy, to complete the sleep log, to administer medication at the proper time, to bring the subject to the scheduled visits or to answer questions regarding the subject's condition or medication use.
  • Lacks a mobile upper extremity to which to attach an actigraphy.
  • Currently participating or has participated in another clinical study within the past 30 days.
  • Demonstrates an unwillingness to abstain from caffeine after 2:00 PM for the duration of the clinical trial participation.
  • Demonstrates an unwillingness to comply with the maximum limit of two alcoholic drinks per day and only one alcoholic drink after 6:00 PM for the duration of the protocol.
  • Uses tobacco products or any other products during nightly awakenings that may interfere with the sleep wake cycle.
  • History of drug abuse or tests positive for the presence of illicit drugs.
  • Donated more than 400 mL of blood within the 90 days preceding the beginning of the study.
  • Diastolic blood pressure greater than 95 mm Hg or a systolic pressure of greater than 160 mm Hg.
  • Body mass index of greater than 36.
  • Alanine transaminase level of greater than two times the upper limit of normal, active liver disease, jaundice or any clinically significant abnormal laboratory findings as determined by the investigator.
  • History of a hypersensitivity or allergies to Ramelteon or melatonin.
  • History of contraindications as noted in the Ramelteon label
  • History of significant stroke or vascular dementia.
  • History of severe renal dysfunction or disease.
  • History of cancer, other than basal cell carcinoma, that has not been in remission for at least 5 years prior to the first dose of study drug. (This criterion does not include those subjects with basal cell or Stage 1 squamous cell carcinoma of the skin.)
  • Any clinically significant movement disorder including but not limited to: akinesia, periodic limb movement disorder, restless leg syndrome, epilepsy, uncontrolled Parkinson's disease, or severe benign prostatic hyperplasia, cardiac asthma, chronic obstructive pulmonary disease.
  • Rapid eye movement behavior disorder or sleep apnea.
  • Any pain syndrome affecting sleep.
  • Is required to take or continues taking any disallowed medication, prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication, including:

    • Fluvoxamine
    • Melatonin
    • Rifampicin

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00325728

Show Show 72 study locations
Sponsors and Collaborators
Layout table for investigator information
Study Director: Medical Director Clinical Science Takeda Global Research and Development
Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Takeda Identifier: NCT00325728    
Other Study ID Numbers: 01-05-TL-375-061
U1111-1115-1644 ( Registry Identifier: WHO )
First Posted: May 15, 2006    Key Record Dates
Last Update Posted: August 14, 2017
Last Verified: August 2017
Keywords provided by Takeda:
Chronic Insomnia
Sleep Initiation and Maintenance Disorder
Drug Therapy
Alzheimer disease
Additional relevant MeSH terms:
Layout table for MeSH terms
Alzheimer Disease
Sleep Initiation and Maintenance Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Sleep Disorders, Intrinsic
Sleep Wake Disorders