CBD for Individuals at Risk for Alzheimer's Disease

Mild Cognitive Impairment Clinical Trial

Official title:

Cannabidiol for Individuals at Risk for Alzheimer's Disease: A Randomized Placebo Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05822362
• Other study ID #: 23-0619
• Status: Recruiting
• Phase: Phase 2
• Start date: January 19, 2024
• Est. completion date: April 2029

Study information

• Verified date: May 2024
• Source: University of Colorado, Denver
• Contact: Raeghan Mueller, PhD
• Phone: 3037242210
• Email: raeghan.mueller[@]cuanschutz.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 236
• Est. completion date: April 2029
• Est. primary completion date: April 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years to 85 Years

Eligibility

Inclusion Criteria:

1. Must be between the ages of 55 - 85 and provide valid informed consent.

2. Participant must receive a diagnosis of Mild Cognitive Impairment after a careful cognitive and functional evaluation by a clinician.

3. Functional Activities Questionnaire (FAQ) score of 8 or less and self-reported ability to function independently

4. Montreal Cognitive Assessment (MoCa) score is between 18-25

5. Participant must have a CDR score of .5 on the Clinical Dementia Rating scale (CDR), which includes an assessment of function and is often used to distinguish MCI from dementia.

6. Must have an informant that will be utilized over the course of the 24 week study (must be the same person throughout study)

7. Participant must pass a test of consent comprehension

8. Must be interested in using CBD to help with cognitive function

9. Must plan on living in the Denver metro area over the next 6 months

10. Able to attend in-person visits at the study site

Exclusion Criteria:

1. Any other central nervous system (CNS) disease that would be expected to affect cognition, Parkinson's disease, multiple sclerosis.

2. Any history of brain injury (e.g., concussion with significant loss of consciousness)

3. Any significant systemic illness or unstable medical condition

4. Current use of Parkinson's medications, antipsychotic medications, anti-seizure medications, or anticholinergic medications

5. Current or lifetime diagnosis of a schizophrenia spectrum disorder, psychotic disorder, bipolar disorder type I & II, cluster B personality disorders (antisocial, borderline, narcissistic, histrionic), eating disorders, as defined by the DSM-5-TR

6. Participation in other clinical studies involving neuropsychological measures being collected more than one time per year.

7. Reported use of other drugs (cocaine, opiates, methamphetamine, MDMA) in the past 60 days or test positive on a urine test for those drugs of abuse at baseline.

8. Report using cannabis, including products with or without CBD, more than four times per month.

9. Recent history of, or meets criteria for major depression with suicidal ideation.

10. Reports use of medical CBD.

11. Liver function enzymes (AST, ALT) that are greater than 2x normal.

12. Currently taking medications known to be contraindicated with Epidiolex (buprenorphine, leflunomide, levomethadyl acetate, lomitapide, mipomersen, pexidartinib, propoxyphene, sodium oxybate, teriflunomide, clobazam, lamotrigine, valproate).

13. Pregnant at the time of study enrollment or unwilling to use contraception through the duration of the study (if not yet post-menopausal)

14. Individuals with potentially reversible causes of mild cognitive impairment (hypothyroidism, Vitamin B12 deficiency).

Related Conditions & MeSH terms

• Alzheimer Disease
• Cognitive Dysfunction
• Mild Cognitive Impairment

Intervention

Drug:
• Cannabidiol
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.

Other:
• Placebo
Placebo arm.

Locations

Country	Name	City	State
United States	University of Colorado - Anschutz Medical Campus	Aurora	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
University of Colorado, Denver

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Biomarkers of Alzheimer's Disease Progression	Changes in plasma levels of N-p-tau181 will be measured in ng/dl.; Changes in plasma Aß42/Aß40 ratio will be measured in ng/dl.; Changes in plasma Neurofilament Light (Nfl) will be measured in ng/dl.; APoE gene will be isolated from peripheral mononuclear cells and measured in ng/dl.	Week 0 to Week 24
Primary	Neurocognitive 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.	Week 0 to Week 24
Secondary	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.	Week 0 to Week 24
Secondary	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.	Week 0 to Week 24
Secondary	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	Week 0 to Week 24
Secondary	Change in plasma lipid biomarkers of inflammation and oxidative stress	Change in plasma levels of 5-iso PGF2aVI, 16-HETE, PGD2 will be measured in ng/dl.	Week 0 to Week 24