Clinical trial NCT06570928: Use of a Cannabinoids as a Treatment Strategy for Alzheimer's Disease
Official title: Use of a Product Containing the Cannabinoids CBD and THC as a Treatment Strategy for Alzheimer's Disease - Clinical Trial Alzheimer's Disease and Cannabis (DAZACANN)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alzheimer Disease
Keywords: Alzheimer Disease
Cannabinoids
Cannabidiol
Tetrahydrocannabinol (THC)
Nervous System Diseases
Lead sponsor: Federal University of Latin American Integration
Sponsor class: OTHER
First posted: 2024-08-26
Enrollment: 72
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 72 patients will be randomized into 2 groups. One group will receive a product containing CBD/THC and the other group will receive a placebo, a compound with the same characteristics, without an active ingredient.
Primary purpose: TREATMENT

Brief summary: Brief Summary:

The objective of the study is to evaluate the effect of cannabinoids on Alzheimer's Disease. This is a double-blind, randomized, placebo-controlled clinical trial. The study aims to recruit patients of both sexes diagnosed with Alzheimer's Disease who are in the mild and moderate stages for treatment with cannabinoids.

The specific objectives of the study are:

Primary Outcome

* To evaluate the effect of Cannabis sativa at low doses according to the Mini-Mental State Examination (MMSE) scale - Memory and Cognition test - in patients with Alzheimer's Disease.

Secondary Outcomes

* To evaluate the effect of Cannabis sativa at low doses according to the Cornell scale - Depression in dementia test.
* To evaluate the effect of Cannabis sativa at low doses according to the GDS scale - Depression in elderly people test.
* To evaluate the effect of Cannabis sativa at low doses according to the QoL scale - Quality of Life test.
* To evaluate the effect of Cannabis sativa at low doses according to the Epworth scale - Drowsiness test.
* To evaluate the adverse effects of Cannabis sativa at low doses given daily for 26 weeks in patients with Alzheimer's Disease.

Participants will use a compound containing CBD/THC 50/5 mg/mL, administered as 0.2 mL once a day. The placebo group will use a compound identical to the treatment but containing only vehicle. To address the questions above, the treated group will be compared with the placebo group over a period of 6 months. Participants will be assessed every 2 months. Additionally, blood and cerebrospinal fluid tests will be conducted to measure specific proteins related to Alzheimer's Disease and inflammatory markers.

Detailed description: Alzheimer's disease (AD) is closely linked to the accumulation of neurotoxins derived from Aβ and tau, leading to cognitive impairment. This project posits that an imbalance in the endocannabinoid system occurs in an AD-dependent manner. Reported connections between dementia, inflammation, Aβ, and alterations in the cannabinoid system in experimental models of AD support this hypothesis. Cannabinoids may restore baseline brain function while avoiding major side effects. Despite extensive research into new AD therapies, no significant improvement has been achieved recently, and there is little consensus on how scientists will innovate to develop a new treatment. Cannabinoid-based therapy has emerged as crucial for the treatment of many diseases considered incurable. The expected results of this project will provide important insights into the ability of cannabinoids to counteract neurochemical imbalance during AD progression, thereby improving memory performance and affecting inflammation as well as Aβ and tau levels.

The key point is to provide evidence that cannabinoids can serve as an efficient treatment for AD while avoiding major side effects. The aim of this project is to determine the effect of cannabinoids in AD patients, evaluating memory and cognition. It is expected that the results will establish that cannabinoids are critical for restoring the baseline function of the endocannabinoid system in AD brains and their beneficial effects. This project may be instrumental in validating new therapeutic approaches for AD.

To evaluate the pharmacological activity of low doses of CBD, a double-blind, randomized, placebo-controlled clinical trial will be conducted for a duration of 6 months. A baseline assessment will be performed, and patients will be evaluated every 60 days for a period of 6 months, totaling 4 evaluation sessions. For this purpose, the following questionnaires will be applied: Mini-Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI), Geriatric Depression Scale (GDS), Alzheimer's Disease Quality of Life version patient, version caregiver and caregiver-patient version, Cornell Depression in Dementia Scale, and Epworth Sleepiness Scale. All questionnaires are references in their assessment domains and are validated for Portuguese/Brazil. In addition to the evaluation scales, biological material will be collected with blood and cerebrospinal fluid samples at baseline and at the end (after 6 months). The following analytes will be measured in the CSF: BDNF, beta-amyloid, Tau protein, TNFα, IL-6, IL-1β, and IL-10. During the research and data collection, patients' conventional treatments will not be altered.

Statistical Analysis Plan SPSS software, version 29.0 will be used for the analyses. For quantitative data, the Shapiro-Wilk distribution test will be performed. Potential associations between qualitative variables will be analyzed using the Chi-Square test with adjusted residual analysis (χ²). The means (±SD) will be analyzed using the Student's t test for independent samples. Medians \[IQR\] will be calculated using the Mann-Whitney U test. Paired quantitative data will be compared individually by group across the analyzed time points using Friedman's ANOVA test.

A generalized estimating equations (GEE) model, linear or with log-gamma link, and Bonferroni correction will be used to simultaneously evaluate quantitative parameters over time and between groups. For these descriptive analyses, data will be presented as means ± standard errors (±SEM). Pearson or Spearman correlations can be performed between variables of interest. For all analyses, the significance level will be set at 5%.

Eligibility criteria: Inclusion Criteria:

* Be over 60 years old;
* Have been diagnosed with AD at least 1 year ago;
* Present mild to moderate symptoms of AD.

Exclusion Criteria:

* Have a diagnosis of other dementias or factors correlated;
* Present psychosis or first-degree relatives with a history from psychosis, schizophrenia, epilepsy;
* Individuals with a history of psychoactive substance abuse will be included in the study;
* Present severe symptoms of AD.

Primary outcomes:
measure: Mini Mental State Exam (MMSE)
timeFrame: The participants will be evaluated before starting treatment, and then every 60 days until 180 days are complete, resulting in 4 evaluations.
Secondary outcomes:
measure: Neuropsychiatric Inventory-Questionnaire (NPI-Q)
timeFrame: The participants will be evaluated before starting treatment, and then every 60 days until 180 days are complete, resulting in 4 evaluations.
measure: Geriatric Depression Scale (GDS)
timeFrame: The participants will be evaluated before starting treatment, and then every 60 days until 180 days are complete, resulting in 4 evaluations.
measure: Quality of Life in Alzheimer's Disease scale (QoL-AD)
timeFrame: The participants will be evaluated before starting treatment, and then every 60 days until 180 days are complete, resulting in 4 evaluations.
measure: Cornell Scale for Depression in Dementia (CSDD)
timeFrame: The participants will be evaluated before starting treatment, and then every 60 days until 180 days are complete, resulting in 4 evaluations.
measure: Epworth Sleepiness Scale (ESS )
timeFrame: The participants will be evaluated before starting treatment, and then every 60 days until 180 days are complete, resulting in 4 evaluations.
measure: Specific markers of Alzheimer's disease: Beta-amyloid 40, beta-amyloid 42, tau protein (fraction 181), and phosphorylated tau protein
timeFrame: Collections will be made at the initial time, before the start of treatment and at the end time, after 180 days.
measure: BDNF (Brain Derived Neurotrophic Factor)
timeFrame: Collections will be made at the initial time, before the start of treatment and at the end time, after 180 days.
measure: Inflammatory markers: TNFα (Tumor Necrosis Factor alpha), IL-6 (Interleukin-6), IL-1β (Interleukin-1 beta), and IL-10 (Interleukin-10)
timeFrame: Collections will be made at the initial time, before the start of treatment and at the end time, after 180 days.
Other outcomes:
measure: Safety Endpoints - UKU Side Effect Rating Scale
timeFrame: The participants will be evaluated before starting treatment, and then every 60 days until 180 days are complete, resulting in 4 evaluations.
Locations:
city: Foz do Iguaçu
country: Brazil
facility: Federal University of Latin American Integration
state: Paraná
Study officials:
affiliation: Universidade Federal de Santa Catarina
name: Taynara Silva, 1
role: PRINCIPAL_INVESTIGATOR
References: