Please select the eligibility criteria that correspond to the clinical trial below.
Title: Nighttime Agitation and Restless Legs Syndrome in People With Alzheimer's Disease
Brief Summary: Nighttime agitation in persons with Alzheimer's disease causes patient suffering, distresses caregivers, and often results in prescriptions for harmful antipsychotics. Effective treatments are lacking because of limited knowledge of the etiology of nighttime agitation. The investigators propose a clinical trial to better elucidate whether a sleep disorder, restless legs syndrome, may be a mechanism for nighttime agitation, and if treatment with gabapentin enacarbil (Horizant®) reduces nighttime agitation, improves sleep, reduces restless legs syndrome behaviors, and reduces antipsychotic medications.


Options:
A: Inclusion Criteria:

* Male or post-menopausal female out-patients diagnosed with Alzheimer's disease
* Patients should have mild to moderate dementia as evidenced by a Mini-Mental State Examination score of 10-24 inclusive at screening
* The patient must show a history of cognitive decline that has been gradual in onset and progressive over a period of at least six months
* There must be evidence of sustained memory deterioration in an otherwise alert patient, plus additional impairment in at least one of the following five areas: orientation, judgement and problem solving, functioning in community affairs, functioning in home and hobbies, or functioning in personal care
* The caregiver resides with the patient and is able to speak with the investigative team about the patient's activities, medication use and adverse events. In addition, the caregiver will participate in assessment interviews and complete questionnaires for themselves and the patients. The caregiver will monitor their own sleep, the patient's sleep, and complete questionnaires regarding sleep patterns and care giving activities

Exclusion Criteria:

* Neurodegenerative disorders such as Parkinson's disease, Pick's disease or Huntington's chorea, Down's syndrome, Creutzfeldt-Jacob disease
* One of the following conditions possibly resulting in cognitive impairment: acute cerebral trauma or injuries secondary to chronic trauma, hypoxic cerebral damage, e.g., post resuscitation (cardiac arrest, post anesthesia, secondary to severe self-poisoning episode, or secondary to severe hypovolemia)
* Patients with the following medical conditions: any history of epilepsy or convulsions except for febrile convulsions during childhood, clinically significant: endocrine disease, metabolic disease, psychiatric disease, cardiovascular disease, peptic ulcer disease, hepatic disease, renal disease, pulmonary disturbances or urinary outflow obstruction
* Use of any agent for the treatment of dementia (approved, experimental or over the counter agents) including patients who have previously received tacrin, donepazil, metrifonate, rivastigmine tartrate, galantamine, or memantine for treatment of Alzheimer's disease
B: 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
C: Inclusion Criteria:

* Aged \>=55 years
* Clinical Dementia Rating (CDR) score of 0.5-3, indicating very mild to severe dementia
* Physician diagnosis of dementia of the Alzheimer's type
* Nighttime agitation, defined as Cohen Mansfield Agitation Inventory, Direct Observation total score \>=35
* Opinion of the participant's physician that medication for agitation is appropriate
* RLS diagnosis by study advanced practice nurse (APN) or registered nurse (RN) (in consult with the participant's physician, and the investigators), using the Behavioral Indicators Test-Restless Legs
* Medically stable, defined as unchanged medications within 14 days and the absence of fever or other signs and symptoms of acute illness or delirium (e.g. urinary tract infection, pneumonia) that may cause agitation or interfere with the study protocol
* Able to swallow medication
* Ambulatory, with and without assistance
* If currently being treated for RLS, may be included if still having RLS symptoms/signs and confirmed as appropriate for inclusion by medical review

Exclusion Criteria:

* Received \>= 50 morphine milligram equivalents per day (MME/d) in the 14 days prior to the randomization decision, because morphine and GEn taken together have a higher incidence of sedation and dizziness than either drug alone
* Currently being treated for RLS with gabapentin or GEn
* Diagnosis of Parkinson's disease (PD) or any other disorder causing tremor because extrapyramidal symptoms may confound RLS diagnosis and actigraphy
* Receiving gabapentin
* Severe psychosis
* Alcohol consumption because combining alcohol and GEn may increase sedation and other adverse events
* Treatment with GEn is contraindicated, such as when a potential participant is receiving multiple antiepileptic drugs, in the opinion of the study APN or RN, participant's physician, or study medical team
* Failure of past treatment with gabapentin or GEn
* Compromised renal function as indicated by creatinine clearance \<15 or on hemodialysis
* Current participation in a clinical trial or in any study that may affect study outcomes
* Determined to be at risk for suicide by the study APN, RN, or participant's physician
* Any condition, that in the opinion of the study APN or RN, participant's physician, or study medical team, makes it medically inappropriate for the patient to enroll in the trial
* Persons living independently in the community without a live-in caregiver (family or hired)
D: Inclusion Criteria:

* Age between 60-99 years
* Clinical diagnosis of Dementia of the Alzheimer's type or Vascular Dementia
* Only subjects with Mini Mental Status Examination scores of greater or equal to 10 will be enrolled.

Exclusion Criteria:

1. Subjects who are too agitated to be able to wear the activity monitors;
2. Subjects who are actively suicidal or homicidal or for whom the clinical treatment team considers participation in the study to be unsuitable;
3. Subjects with untreated primary sleep disorders;
4. Subjects who receive hypnotic medications during their participation in the study; Subjects who received hypnotic medications prior to enrollment may participate in the study if they agree to stop receiving hypnotic medications (with their attending physician's approval);
5. Subjects who are receiving over the counter sleep aids;
6. Subjects who can not commit to abstaining from alcohol use while in the study;
7. Subjects with known anaphylactic reaction or angioedema with Zolpidem CR.

Answer: C