Improving Sleep and AD Biomarkers

Alzheimer Disease Clinical Trial

Official title:

Improving Sleep and Alzheimer's Disease (AD) Biomarkers: A Pilot Randomized Clinical Trial (RCT) of Citicoline

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06029894
• Other study ID #: STUDY00006047
• Secondary ID: 1R61AG080606-01
• Status: Recruiting
• Phase: N/A
• Start date: December 15, 2023
• Est. completion date: December 2024

Study information

• Verified date: January 2024
• Source: Emory University
• Contact: Victoria Pak, PhD, MS, MTR
• Phone: 470-296-0081
• Email: victoria.m.pak[@]emory.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this research is to learn whether a dietary citicoline supplement will impact sleep and cognition. Cognitive disorders include such things as memory disorders and mild cognitive impairment. The investigators are studying persons with mild cognitive impairment (MCI). For this population, the team will assess whether citicoline also impacts biomarkers, a marker of the patient's biological state, in their body.

The investigators are interested in learning more about a dietary supplement called citicoline and how it helps sleep, cognition, and markers of Alzheimer's. Previous studies have evaluated this dietary supplement and shown that citicoline may impact cognitive decline. The investigator would like to evaluate if citicoline will also impact sleep and markers of Alzheimer's. This dietary supplement has been assessed in older adults and found to be well tolerated. Citicoline has been used safely in cognitive impairment populations at the same dosage.

Description:

This is a randomized double-blind placebo-controlled pilot trial. To assess the hypothesis in this proposed study, the investigator will leverage infrastructure from the Emory Alzheimer's disease research center (ADRC), ADRC-affiliated centers, mild cognitive impairment, related research cohorts with potential eligible participants interested in participating in future studies, the Emory Sleep Center, and also recruit from the community. The research team will be actively recruiting individuals with MCI with confirmed medical diagnoses. The investigator will also collect data from personal interviews on prior medical diagnoses from the medical record along with current medication usage. Researchers will also obtain available baseline AD biomarker data from participants at baseline if they have cerebrospinal fluid (CSF) and/or blood data available on AD biomarkers within the past year from prior research studies, the investigators will use this data for the study records which will serve as their 'baseline' AD biomarker level). AD biomarkers of interest include Amyloid-Beta 1-42 (Aβ42), t-tau, and P-tau181. Should participants not have this data available at baseline, the research team will conduct a blood draw for AD biomarker levels at baseline and at follow-up.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

Inclusion Criteria:

• Age: 60 years or older

• Diagnosis of Mild Cognitive Impairment (MCI)

• Pittsburgh Sleep Quality Index total score >5 or Epworth Sleepiness Scale score of = 10

• Read and understand English

• Have Internet and email access

Exclusion Criteria:

• No telephone access

• Must not be taking any medication known to affect rapid eye movement (REM) sleep (or sleep architecture in general)

• Use of choline supplements.

• Epilepsy or head trauma resulting in unconsciousness in the past two years

• Known allergic reactions to components of Citicoline

• 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, severe/unstable psychiatric disorders, moderate to severe obstructive sleep apnea, restless legs syndrome or periodic limb movement disorder

• History of alcohol dependence and drug abuse

• Night shift workers or those in situations where they regularly experience jet lag or have irregular work schedules

Related Conditions & MeSH terms

• Alzheimer Disease
• Cognitive Dysfunction
• Mild Cognitive Impairment

Intervention

Dietary Supplement:
• Citicoline Supplement
Participants with MCI will receive dietary citicoline supplements. 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. Participants will undergo a blood draw of approximately 20 ml at baseline and at follow-up.

Other:
• Placebo
Participants with MCI 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. Participants will undergo a blood draw of approximately 20 ml at baseline and at follow-up.

Locations

Country	Name	City	State
United States	Emory University School of Nursing	Atlanta	Georgia
United States	Goizueta Alzheimer's Disease Research Center	Atlanta	Georgia

Sponsors (2)

Lead Sponsor	Collaborator
Emory University	National Institute on Aging (NIA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in 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
Primary	Change in 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 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
Primary	Change in percentage of the rapid eye movement (REM) sleep	The change in % REM sleep will be measured using The Sleep Profiler using the polysomnography 2 (PSG2), which is an Electroencephalogram (EEG) Sleep Monitor that is an FDA-cleared, easily applied, wireless EEG device developed and validated to measure sleep architecture for in-home sleep studies. This will be worn for 2 nights at baseline and again for 2 nights at follow-up.	Baseline and 3 months
Primary	Change in sleep duration	Average sleep duration (hours) will be measured via a subjective 7-day sleep diary that collects subjective sleep/wake patterns and naps. It is the "gold standard" for subjective sleep assessment of sleep duration. It will be filled out by the participant in conjunction with the caregiver.	Baseline and 3 months
Primary	Change in plasma choline levels	Blood draws will be made at baseline and follow-up.	Baseline and 3 months
Primary	Change in beta-amyloid 42 levels	Levels of beta-amyloid 42. A lumbar puncture (LP) will be performed at 3 months in participants who have already had a previous LP. For those who don't have a previous LP performed, blood samples will be drawn before starting the study medication and at follow-up.	Baseline and 3 months
Primary	Change in tau and phospho-tau levels	Levels of tau, and phospho-tau will be measured. A lumbar puncture (LP) will be performed at 3 months in participants who have already had a previous LP. For those who don't have a previous LP performed, blood samples will be drawn before starting the study medication and at follow-up.	Baseline and 3 months