Improving Sleep and Cognition in Alzheimer's Disease

Study Overview
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Brief Summary
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Cognitive disorders include such things as memory disorders, mild cognitive impairment, and Alzheimer's disease (AD). The purpose of the study is to learn more about whether a dietary citicoline supplement will improve sleep and cognition. Sleep disturbances currently afflict approximately 25-44% of those with AD, resulting in decreased quality of life for those with AD and their caregivers and are a major driver of institutionalization. Previous studies have tested this dietary supplement in Alzheimer's disease and shown that citicoline may improve cognitive decline. The research team would like to see if citicoline will also improve sleep. The citicoline that will be provided is made by Kyowa Hakko Pharma Chemical Company. This dietary supplement has been tested for Alzheimer's disease and found to be well tolerated. Citicoline has previously been used safely in other Alzheimer's disease populations at the same dosage.

Detailed Description
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The research team will test these hypotheses via a randomized, double-blind, placebo-controlled pilot study of citicoline in individuals with AD. Participants will be recruited from the Alzheimer's Disease Research Center (ADRC) and from the community in the surrounding Atlanta area. This will be a 3-month randomized, double-blind, placebo-controlled trial comparing citicoline and placebo in a well-characterized cohort of 20 individuals with AD. Subjective sleep measures will be measured via the Pittsburgh Sleep Quality Index (for measurement of sleep quality) and Epworth Sleepiness Scale (for measurement of sleepiness). For neuropsychological and cognition will be measured measures, the research team will employ the Rey Auditory Verbal Learning Test (RAVLT), Trail Making Test (TMT) Parts A & B, and the Montreal Cognitive Assessment (MOCA). Those participating in the ADRC parent study or recruited from the community and diagnosed with AD in their medical record and aged 18 and over are eligible to participate. Eligible participants will be enrolled in a two-treatment trial comparing the effects of citicoline (1000 mg once per day with or without food) to a placebo. There will be a baseline (T0) visit and a follow-up 3 months later (T1) as a separate visit.

Official Title
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Improving Sleep and Cognition in Alzheimer's Disease: A Pilot RCT of Citicoline

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Dietary Supplement: Citicoline supplement
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants who are diagnosed with AD and confirmed from the medical record. At least 18 years of age living within the continental United States Read and understand English Have Internet and email access (this criterion applies to the legally authorized representatives) Exclusion Criteria: No telephone access Epilepsy or head trauma resulting in unconsciousness in the past two years Presence of chronic obstructive pulmonary disease, asthma, severe cardiac insufficiency (congestive heart failure, myocardial infarction), type I diabetes, vitamin B12 or folic acid deficiency, liver cirrhosis, thyroid dysfunction, rheumatoid arthritis, chronic renal failure, and/or psychiatric disorders, obstructive sleep apnea, restless legs syndrome or periodic limb movement disorder History of alcohol dependence and medication abuse Night shift workers or those in situations where they regularly experience jet lag, or have irregular work schedules, since circadian misalignment may alter markers of inflammation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Citicoline Supplement<br>Participants with AD will receive a dietary citicoline supplement | Dietary Supplement: Citicoline supplement<br>* Participants with AD will receive a dietary citicoline supplement. Subjective sleep measures will be measured via the Pittsburgh Sleep Quality Index (for measurement of sleep quality) and Epworth Sleepiness Scale (for measurement of sleepiness). Cognition will be measured by Rey Auditory Verbal Learning Test (RAVLT), Trail Making Test (TMT) Parts A & B, and the Montreal Cognitive Assessment (MOCA). Participants will complete all questionnaires at baseline and at follow-up at 3 months.<br>|
| Placebo Comparator: Placebo<br>Participants with AD will receive a placebo supplement | Other: Placebo<br>* Participants with AD will receive a placebo supplement. Subjective sleep measures will be measured via the Pittsburgh Sleep Quality Index (for measurement of sleep quality) and Epworth Sleepiness Scale (for measurement of sleepiness). Cognition will be measured by Rey Auditory Verbal Learning Test (RAVLT), Trail Making Test (TMT) Parts A & B, and the Montreal Cognitive Assessment (MOCA). Participants will complete all questionnaires at baseline and at follow-up at 3 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the impact on sleep by the administration of the citicoline supplement. | Assessment will be performed by completing the Pittsburgh Sleep Quality Index (PSQI): This questionnaire is used to measure subjective sleep quality. It has strong validity and reliability in clinical populations and consists of 19 items asking about sleep disturbances over the past month with 7 dimensions. Each dimension scores 0 (no difficulty) to 3 (severe difficulty) and the sum of these scores yields a global sleep quality score that ranges from 0-21. Higher scores indicate greater difficulty sleeping. This questionnaire can be filled out by the participant, caregiver, or both as appropriate. | Baseline and 3 months | 
| Change in the impact on daytime sleepiness by the administration of the citicoline supplement. | Assessment will be performed by completing the Epworth Sleepiness Scale (ESS): The ESS is a clinical and research standard used to assess perceived daytime sleepiness over the past month. It is a self-administered validated questionnaire and takes approximately 2-3 minutes to fill out. Respondents are asked to rate how likely they are to doze off in 8 situations, from 0 (would never dose) to 3 (high chance of dozing). Any score of 10 or above is considered an indicator of pathologic sleepiness. This questionnaire can be filled out by the participant, caregiver, or both as appropriate. | Baseline and 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To examine how a change in sleep correlates with changes in cognitive function with the administration of citicoline. | Assessment of the cognitive function will be performed using the Montreal Cognitive Assessment (MoCA): MoCA assesses global cognitive function and is a rapid screening instrument that takes approximately 10 minutes. It assesses different cognitive domains: attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. This questionnaire will already be administered through the ADRC to the participant at their baseline visit, the researchers will measure separately at their follow-up visit at 3 months. | Baseline and 3 months | 
| To examine how a change in sleep correlates with changes in memory function with the administration of citicoline. | The research team will use the Rey Auditory Verbal Learning Test (RAVLT): RAVLT evaluates the nature and severity of memory dysfunction and is used to track changes in memory function in patients over time. It is designed to present a list of 15 words across five consecutive trials. The list is first read aloud to the participant, and the participant is immediately asked to recall as many words as possible. | Baseline and 3 months | 
| To examine how a change in sleep correlates with changes in executive functioning with the administration of citicoline. | Assessment will be performed using the Trail Making Test (TMT) Parts A & B: TMT assesses executive functioning. The test consists of two parts-Part A and Part B. In Part A, participants are asked to draw lines sequentially connecting 25 numbers distributed on paper. In Part B, in contrast, participants are asked to draw lines sequentially, while alternating between numbers and letters. The time spent to complete the task will be recorded for evaluation. | Baseline and 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sleep disturbance