Clinical trial NCT05432206: MEDical CANnabis for Improving Symptoms During Severe DEMentia Disorders in Long-term Care Facility in Geneva
Official title: Randomized Double-blind Cross-over Placebo-controlled Trial to Study the Impact on Behavioral and Psychological Symptoms of Dementia of Medical Cannabinoids (CBD/THC) in Patients with Severe Dementia in Long-term Care Facilities in Geneva
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Dementia with Behavioral Disturbance
Keywords: Dementia
Medical cannabis
Cannabinoids
Behavioral symptoms
Lead sponsor: Fondation pour l'accueil et l'hébérement des personnes âgées
Sponsor class: OTHER
Collaborators: name: University Hospital, Geneva
First posted: 2022-06-27
Enrollment: 27
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The behavioral and psychological symptoms of dementia affect up to 80% of long-term facilities residents with severe dementia. They seriously alter the quality of life of patients, relatives, and health professionals. Management involves correcting somatic and psychiatric factors and implementing non-drug interventions. Nevertheless, often drug treatments must be introduced with the limitations related to their effectiveness and adverse effects.

The investigators hypothesize that medical cannabinoids will improve neuropsychiatric and behavioral symptoms of patients with severe dementia.

The investigators assessed the feasibility and safety of administering a cannabis oil that contains tetrahydrocannabinol (THC) and Cannabidiol (CBD) during an initial study of about two years, observing an overall improvement, excellent tolerance to the treatment, and the possibility of reducing or even stopping other drugs.

This research project aims to study the efficacy of medical cannabis oil in improving the quality of life of dementia patients experimenting with behavioral and psychological symptoms.

Detailed description: The study design is a placebo-controlled cross-over trial. The patients, the relatives, the health care professionals, and the study staff will be blinded.

Medical cannabis treatment is a cannabis oil that contains THC and CBD in a 1:2 ratio. The initial dose of 7 drops (2.5 mg THC and 5 mg CBD) will be gradually augmented and adjusted individually to a maximum of 56 drops (20 mg THC and 40 mg CBD) per day, divided into two administrations. Placebo is an edible oil with the same color, smell, and flavor as medical cannabis oil given with the same dosage scheme.

Patients will take medical cannabis oil for 8 weeks, in addition to their usual treatments.

The study is divided into two 8-week periods. Participants will be randomized 1:1 between cannabinoids/placebo and placebo/ cannabinoids sequences and will receive the cannabis oil during one of these periods and the placebo during the other.

Participants will observe a wash-out week between the two study periods, and a final observation week without treatment intake is planned at the end of the second period.

Rating scales to evaluate the efficacy will be assessed before treatment, after 28 days, at the end of periods, and at the end of the study. Blood pressure will be evaluated daily. Vital signs, blood formula, and the reduction or discontinuation of other drugs will be recorded periodically. In addition, the health professionals' and relatives' appraisals will be recorded at five-time points.

A blood test at the beginning and the end of each period will allow the evaluation of the potential drug-drug interactions and the pharmacokinetics of cannabinoids. The cytochromes P450 (1A2, 2B6, 2C9, 2C19, 2D6, 3A4/5) enzymatic activity will be evaluated by phenotyping after Geneva micro-cocktail intake. The therapeutic drug monitoring will be measured at a steady-state characterizing the plasma through levels of THC, its two metabolites, 11-hydroxy-tetrahydrocannabinol and free carboxy-tetrahydrocannabinol, and CBD.

Eligibility criteria: Inclusion Criteria:

* Patients with severe dementia from different origins (Alzheimer's disease, vascular, mixed)
* Clinical Dementia Rating ≥3
* Persisting behavior problems (Neuropsychiatric Inventory \[NPI\] score \> 10) notwithstanding optimal conventional treatment
* SARS-CoV-2 recovered for two weeks, or SARS-CoV-2 fully vaccinated
* Consent obtained from the representative in the medical field according to art 378 Swiss Civil Code (SCC)

Exclusion Criteria:

* Severe organ deficiency such as cardiac, pulmonary, hepatic, renal insufficiency, or unstable heart rhythm
* Symptomatic orthostatic hypotension
* Major changes or instability of psychotropic medication in the week preceding the study enrolment
* Having taken THC and/or CBD in the 7 days before enrolment
* Hemoglobin \< 10 g/dl
* Severe kidney failure defined by cockcroft calculation \<30 ml/mn
* Alanine aminotransferase and aspartate aminotransferase \> 3x upper limit of normal
* Any other medical conditions that would prevent participation in the whole study protocol.

Primary outcomes:
measure: Cohen-Mansfield Agitation Inventory Scale (CMAI)
timeFrame: 4 and 8 weeks - after 1 week washout
Secondary outcomes:
measure: Neuropsychiatric Inventory (NPI)
timeFrame: 4 and 8 weeks - after 1 week wash-out
measure: Unified Parkinson disease rigidity scale (UPDRS)
timeFrame: 4 and 8 weeks - after 1 week wash-out
measure: Pain (Doloplus)
timeFrame: 4 and 8 weeks - after 1 week wash-out
measure: Daily activity
timeFrame: 4 and 8 weeks - after 1 week wash-out
measure: Behavioral Trouble
timeFrame: 4 and 8 weeks - after 1 week wash-out
measure: Team
timeFrame: 4 and 8 weeks - after 1 week wash-out
measure: Family
timeFrame: 4 and 8 weeks - after 1 week wash-out
measure: Evolution of dosages for each patient
timeFrame: 4 and 8 weeks
measure: Change in enzymatic activity
timeFrame: 8 weeks
measure: Therapeutic Drug Monitoring
timeFrame: 8 weeks
measure: Endocannabinoids
timeFrame: 8 weeks
Other outcomes:
measure: Blood Count 1
timeFrame: 8 weeks
measure: Blood Count 2
timeFrame: 8 weeks
measure: Blood Count 3
timeFrame: 8 weeks
measure: Blood Count 4
timeFrame: 8 weeks
measure: Blood pressure
timeFrame: through study completion, an average of 5 months
Locations:
city: Geneva
country: Switzerland
facility: FAHPA
Study officials:
affiliation: HUG
name: Sophie Pautex, Prof.
role: PRINCIPAL_INVESTIGATOR
References: