Quetiapine for the Treatment of Insomnia in Alzheimer's Disease

Alzheimer's Disease Clinical Trial

Official title:

Quetiapine for the Treatment of Insomnia Associated With Alzheimer's Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00232570
• Other study ID #: 05-234
• Status: Recruiting
• Phase: N/A
• First received: September 30, 2005
• Last updated: May 4, 2009
• Start date: November 2005
• Est. completion date: January 2010

Study information

• Verified date: May 2009
• Source: University of Vermont
• Contact: Sally Ross-Nolan, M.S.
• Phone: 802-847-9488
• Email: sally.nolan[@]vtmednet.org
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The primary hypothesis is that quetiapine will improve sleep in persons with Alzheimer's Disease (AD), with higher doses producing greater total sleep time and sleep efficiency.

Description:

Quetiapine is frequently used to treat psychosis in patients with Alzheimer's disease (AD) and other dementias. These patients commonly have sleep disturbances that include nighttime awakenings with confused, agitated behaviors. These awakenings impose a great challenge for caregivers, especially family caregivers whose own sleep is disrupted as a result of the patient's awakenings. Sleep disturbance can lead to nursing home placement3 and may add to cognitive impairment of patients.

There is no medication proven to be safe and effective in the treatment of sleep disorders in patients with dementia. Antipsychotic medications are often prescribed at bedtime in the hopes that they will aid sleep and reduce agitation and psychosis associated with these awakenings. Sleep disturbance is more common in AD patients with moderate to severe disease, and these patients are more likely to have psychosis and to be recruited from long-term care facilities. We recently conducted the only multicenter clinical trial of a drug for sleep disturbance in AD. The study, completed under the auspices of the NIA's Alzheimer's Disease Cooperative Study, investigated melatonin as a sedative-hypnotic agent for AD patients. We found melatonin to be of no benefit on objective measures, although there were positive trends in the data and a significant improvement on subjective measures (caregiver ratings of patients' sleep) in one of the melatonin groups relative to placebo. No other large trial in AD subjects has been reported in the literature for drugs with potential benefit for AD patients with sleep disturbances. There are several reasons why this population needs to be specifically studied. Patients with AD tend to have highly fragmented sleep, with many nocturnal awakenings. They have significant daytime sleepiness that might affect daytime cognitive function and behavior. These patients tend to be older, with sensitivity to drug side effects.

People with neurodegenerative diseases such as AD may respond differently to CNS-active medications. Finally, this population represents a large and growing cohort of patients that deserve individual study of their unique problems.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 18
• Est. completion date: January 2010
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 55 Years to 90 Years

Eligibility

Inclusion Criteria:

1. Age 55-90 years.

2. Diagnosis of possible or probable AD as defined by NINCDS-ADRD criteria.

3. Sleep disturbance defined by mean score of 3 on first six items of the SDI.

4. Family member able to provide surrogate informed consent.

5. Live-in caregiver able to monitor medication and serve as informant on questionnaires.

6. Caregiver who is fluent in English.

7. Be able to ingest oral tablets.

8. Be able to avoid caffeinated and alcoholic beverages during the study period.

9. A neuroimaging study at the time of initial diagnosis, or any time since that is consistent with AD and effectively rules out dementia related only to stroke, hydrocephalus or other neurological condition.

Exclusion Criteria:

1. Medical disorders that may account for sleep disturbance, especially delirium, Major Depressive Disorder (DSMIV) and severe or significant acute or chronic pain.

2. Have acute or unstable medical conditions including renal failure, abnormal liver function, cardiac arrhythmia, sitting blood pressure below 110/70 or above 140/100 or postural blood drop 20 mm Hg.

3. Symptoms suggesting other sleep disorders (e.g., periodic limb movement disorder, restless legs syndrome, obstructive sleep apnea syndrome), may be present but in the opinion of the PI, do not account for the primary symptoms of insomnia.

4. Sleep disturbance symptoms that suggest a parasomnia. Parasomnias may include behavioral manifestations of epileptiform activity or REM Behavior Disorder (RBD).

5. Previous treatment failure with quetiapine of AD-associated sleep disturbances, or intolerance of quetiapine in a previous treatment trial.

6. Concomitant treatment with another antipsychotic or sedative-hypnotic medication, including trazodone.

7. Evidence of a major mental disorder other than dementia, such as major depression or schizophrenia.

8. Stable doses (for 4 weeks prior to study entry) of antidepressant, antiepileptic mood stabilizer, or acetylcholinesterase inhibitor medication will be allowed, but initiation or recent changes in the dose of such medications will be prohibited.

9. Benzodiazepines within 2 weeks of study entry will not be allowed.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease
• Insomnia

Intervention

Drug:
• quetiapine

Locations

Country	Name	City	State
United States	Fletcher Allen Health Care-Clinical Neuroscience Research Unit	Burlington	Vermont

Sponsors (3)

Lead Sponsor	Collaborator
University of Vermont	AstraZeneca, National Center for Research Resources (NCRR)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary objective is to determine whether quetiapine can increase total sleep time and reduce time awake in patients with AD and sleep disturbance.
Secondary	Dose-response relationship of quetiapine and sleep in AD patients?
Secondary	Are there sleep architecture changes from quetiapine?
Secondary	Do the primary sleep variables change relative to placebo at any weekly time or dose point?
Secondary	Are caregivers, blind to treatment status, able to detect changes in sleep quality in the patients for quetiapine relative to placebo?
Secondary	Does quetiapine used at single bedtime dosing for potential nighttime soporific effect have a measurable impact on neuropsychiatric symptoms other than insomnia?