Clinical trial NCT01023672: "Pilot Study of Armodafinil in Patients With Dementia With Lewy Bodies"
Official title: An Open Label, Single-Center Pilot Study of Armodafinil in Patients With Dementia With Lewy Bodies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Dementia With Lewy Bodies
Keywords: Dementia with Lewy Bodies
hypersomnolence
cognition
neuropsychiatric morbidity
quality of life
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: Cephalon
name: National Institute on Aging (NIA)
First posted: 2009-12-02
Enrollment: 20
Sex: ALL
Minimum age (years): 50
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This research study is to examine the effects of the study medication Armodafinil in patients with dementia with Lewy bodies (DLB).

DLB is associated with memory and other thinking problems, excessive daytime sleepiness, hallucinations, delusions, apathy, and reduced quality of life.

One type of medication that could potentially improve daytime sleepiness, memory and thinking skills, hallucinations, delusions, apathy, and quality of life is known as a wake-promoting medication. Armodafinil is a wake-promoting medication that has been developed for treatment of patients with narcolepsy, sleep apnea, and other disorders which cause excessive daytime sleepiness.

The drug used in this study is considered investigational, which means it has either not been approved by the Food and Drug Administration (FDA) for routine clinical use or for the use described in this study. However the FDA has allowed the use of this drug/device in this research study.

In this study, patients with DLB will receive daily oral Armodafinil tablets, and their response to treatment will be assessed over 12 weeks. This study does not involve any placebo medication, so all patients will receive Armodafinil treatment.

Detailed description: 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)

Eligibility criteria: 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

Primary outcomes:
measure: Mean Initial Sleep Latency as Measured by the Maintenance of Wakefulness Test (MWT)
timeFrame: baseline, 12 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Bradley F Boeve, MD
role: PRINCIPAL_INVESTIGATOR
References: