This is a double-blind, randomized controlled trial designed to test the effects of cannabidiol (CBD) on validated biomarkers of Alzheimer's disease (AD) progression, and behavioral, neurocognitive, and clinical measures, with putative mechanisms of action.
To better understand the effects of hemp-derived CBD with and without a small amount of THC, we propose a Phase II randomized clinical trial (RCT) to examine the clinical effects of Full Spectrum CBD (fsCBD, contains less than 0.3% THC) vs. Broad Spectrum CBD (bsCBD, does not contain THC), vs. a matching placebo in a population of individuals diagnosed with mild cognitive impairment (MCI). This is a double-blind, placebo-controlled, parallel group study designed to assess the efficacy of fsCBD and bsCBD, compared to a placebo control, on biomarkers of Alzheimer's disease progression, cognitive function, pain, sleep quality, anxiety, oxidative stress, and inflammation. If eligible for the study, subjects will be randomized to receive one of the conditions for 24 weeks. The current study will test the hypothesis that a moderate dose of CBD will improve measures of Alzheimer's disease progression, cognitive function, pain, sleep quality, anxiety, oxidative stress, and inflammation as compared to placebo. The study will also test whether endocannabinoids mediate the effects of CBD on these outcomes.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
236
The current study will directly test the hypothesis that a moderate dose of CBD improves markers of Alzheimer's progression, cognitive function, sleep, pain, anxiety, oxidative stress, and inflammation.
Placebo arm.
University of Colorado - Anschutz Medical Campus
Aurora, Colorado, United States
RECRUITINGNeurocognitive Function
The following assessments will be used to inform an aggregate measure of neurocognitive function: * The Clinical Dementia Rating Scale is a 5-point scale used to characterize six domains of cognitive and functional performance applicable to Alzheimer disease and related dementias. Higher scores indicate worse cognitive impairment. * NIH-Toolbox Cognitive Battery (NIH-TB CB) assessments are used to detect and measure specific aspects of cognition, including crystallized intelligence, psychomotor function, executive function, attention, and working memory. * Rey Auditory Verbal Learning Test to evaluate working memory and the Digit Symbol Substitution Task to evaluate global cognitive operations. * Montreal Cognitive Assessment (MoCa) * Functional Activities Questionnaire (FAQ) will be used to measure changes in dementia risk over the course of the clinical trial.
Time frame: Week 0 to Week 24
Biomarkers of Alzheimer's Disease Progression
* Changes in plasma levels of N-p-tau181 will be measured in ng/dl. * Changes in plasma Aβ42/Aβ40 ratio will be measured in ng/dl. * Changes in plasma Neurofilament Light (Nfl) will be measured in ng/dl.
Time frame: Week 0 to Week 24
Change in pain
* The PROMIS Pain Intensity 1a questionnaire consists of two items asking about the participant's level of pain on average and at its worst in the past 7 days. Participants are asked to rate their pain on a scale from 0 (no pain) to 10 (worst imaginable pain). * The PROMIS Short Form v1.1 - Pain Interference - 6b scale will be used to assess how disruptive pain was over the past 7 days. There are six questions with a total score of 30-higher scores indicate more interference.
Time frame: Week 0 to Week 24
Change in sleep
* The PROMIS Sleep Disturbance 4a assesses self-reported perceptions of sleep quality, sleep depth, and restoration associated with sleep. Scores range from 4-20, with higher scores indicating worse sleep outcomes. * The PROMIS Sleep-Related Impairment 4a assesses perceptions of alertness, sleepiness, tiredness, and perceived functional impairments during usual waking hours due to sleep problems. Scores range from 4-20, with higher scores indicating worse sleep-related impairment. * The PROMIS Short Form v1.0 - Fatigue 4a measures subject fatigue over the past 7 days. Scores range from 4-20, with higher scores indicating more fatigue.
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Time frame: Week 0 to Week 24
Change in anxiety
-The Depression Anxiety Stress Scale is a 21-item self-report instrument for measuring the three related negative emotional states of depression, anxiety, and tension/stress. Higher scores indicate worse anxiety
Time frame: Week 0 to Week 24
Change in plasma lipid biomarkers of inflammation and oxidative stress
Change in plasma levels of 5-iso PGF2αVI, 16-HETE, PGD2 will be measured in ng/dl.
Time frame: Week 0 to Week 24