"Pilot Study of Armodafinil in Patients With Dementia With Lewy Bodies"

In patients with DLB, the following aims/objectives will be addressed by comparing data on key measures at baseline and at 4 and 12 weeks of therapy:

Primary Aims - to test the hypotheses that armodafinil therapy at 150-250 mg every morning:

• will result in improvement in excessive daytime sleepiness as measured by the Epworth Sleepiness Scale (ESS) and Maintenance of Wakefulness Test (MWT) (Aim 1A)
• will result in improvement in the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog) (Aim 1B)
• will result in improvement in the Alzheimer's Disease Cooperative Study-Clinician's Global Impression of Change (ADCS-CGIC) (Aim 1C)
• will be well-tolerated with no significant side-effects present (Aim 1D)

Secondary Aims - to test the hypotheses that armodafinil therapy at 150-250 mg every morning will result in improvement in:

• cognition as measured by the Mini-Mental State Examination (MMSE) and other focused neuropsychological tests (Aim 2A)
• neuropsychiatric morbidity, particularly apathy, depression, visual hallucinations, and delusions, as measured by the Neuropsychiatric Inventory (NPI) (Aim 2B)
• functional status as measured by the Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) (Aim 2C)
• patient and caregiver quality of life (QOL) as measured by the linear analog scale (LASA) (Aim 2D)

Inclusion criteria

• Diagnosis of clinically possible or probable DLB using established criteria
• Age 50-90 inclusive
• Epworth Sleepiness Scale score of 8 or greater
• MMSE score between 10 and 26 inclusive
• No active medical disorder that could preclude participation in a drug treatment trial over a 12 week protocol
• Stable medication regimen over previous four weeks
• Absence of psychotropic medications at doses viewed by the clinician to be significantly impacting the patient's alertness during wakefulness
• Absence of clinically significant primary sleep-related breathing disorder causing sleepiness as demonstrated by polysomnography (PSG) [ie, no significant upper airway resistance syndrome (UARS), obstructive sleep apnea (OSA), nor central sleep apnea (CSA) as reflected by a combined respiratory disturbance index (RDI) <15] OR adequate documentation of efficacy of treatment for UARS, OSA, and CSA
• Caregiver that is with the patient at least 4 hours/day for at least 5 days per week
• Patient and caregiver willing and able to participate in all study-related procedures
• Patient is capable of giving informed consent, or if appropriate, has caregiver capable of giving consent on the subject's behalf.

Exclusion criteria

• Does not fulfill criteria for clinically possible or probable DLB
• Age <50 or >90
• Women with intact uterus and not post-menopausal unless pregnancy test performed at screening is negative
• Epworth Sleepiness Scale score less than 8
• MMSE score <10 or >26
• Active medical disorder that could preclude participation in a drug treatment trial over a 52 week protocol, such as:

• Hypertension with BP readings exceeding 150 mm Hg systolic and 90 mm Hg diastolic
• Hypersensitivity to modafinil, armodafinil, or any other conventional stimulants
• Myocardial infarction or cerebral infarct over preceding year, stable or unstable angina, known symptomatic coronary artery disease
• History of left ventricular hypertrophy or mitral valve prolapse
• History of chronic or paroxysmal atrial fibrillation, chronic or paroxysmal atrial flutter, ventricular fibrillation, or ventricular tachycardia
• History of cancer over preceding 1 year (excluding squamous or basal cell carcinoma of the skin)
• History of Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS)
• Pulmonary disease requiring oral or inhalatory medications
• Any other medical disorder considered by the study physicians as inappropriate for any wake-promoting medication
• Medication regimen has not been stable over preceding four weeks
• Concurrent use of lamotrigine or oxcarbazepine
• Presence of over-the-counter and prescription psychotropic medications at doses viewed by the clinician to be significantly impacting the patient's alertness during wakefulness, such as:

• Clonazepam > 1 mg/night
• Seroquel > 100 mg/night
• Zyprexa > 10 mg/night
• Presence of another clinically-significant primary sleep disorder (eg, UARS, OSA, CSA) that is not being treated
• Clinically significant abnormalities on screening ECG or laboratory tests
• Patient or caregiver unwilling or unable to participate in all study-related procedures
• Caregiver is not with patient at least 4 hours/day for at least 5 days/week
• Patient or caregiver unwilling or unable to provide informed consent
• CT or MRI evidence of a clinically significant structural lesion that could account for the participants dementia