The Effect of Cannabis on Dementia Related Agitation and Aggression

NCT03328676 | Completed Phase 2 DMC

• 1 other identifier: TO_D02_2016
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

The most common syndrome in patients with severe dementia is agitated behavior, which is often characterized by a combination of violent behavior (physical or verbal), restlessness, and inappropriate loudness. The treatment options for this syndrome are limited and lead to severe side effects. In vivo experiments on animals and clinical studies on adults show that cannabinoids could have a beneficial effect on behavioral disorders in general, and in dementia-related disorders in particular. Additionally, medical cannabis patients have reported that cannabis aids in pain relief, increased appetite, and a sense of calm and peace of mind. Elderly patients suffering from dementia that experience this syndrome could also benefit from other quality of life aspects of the cannabis treatment such as reduction in medication consumption, weight gain and improvement of sleep.

Conditions

Agitation Related to Dementia

Outcome Measures

Primary Outcomes (1)

• Change in score of Cohen-Mansfield Agitation Inventory (CMAI)

  Proportion of subjects achieving a decrease of four or more points on the Cohen-Mansfield Agitation Inventory (CMAI), a 29-item scale that measures the types and frequencies of agitated behaviors, each rated on a 7-point scale of frequency, where higher scores indicate greater agitation severity.

  week 16

Secondary Outcomes (1)

• Change in score of Neuropsychiatric Inventory-Nursing Home Version (NPI-NH)

  week 16

Study Arms (2)

"Avidekel " cannabis oil 20:1 CBD:THC

EXPERIMENTAL

The cannabis oil will be mad out of extract from the Avidekel strain and olive oil. Avidekel oil containing Δ9-Tetra-Hydrocannabinol (Δ9-THC) and Cannabidiol (CBD) in a 1:20 ratio and at a concentration of 30% CBD and 1.5% Δ9-THC. Each Avidekel oil drop is approximately 0.04 ml in volume containing about 12 mg CBD and 0.6 mg Δ9-THC.

Drug: Cannabis

placebo oil

PLACEBO COMPARATOR

Patients in the control group will receive placebo.

Drug: Placebo oil

Interventions

Cannabis DRUG

Patients will receive study medication as drops applied under the tongue 3 times a day - morning, noon and evening, at a minimum of 4hr apart between administrations.

Also known as: CBD-A

"Avidekel " cannabis oil 20:1 CBD:THC

Placebo oil DRUG

Patients will receive study medication as drops applied under the tongue 3 times a day - morning, noon and evening, at a minimum of 4hr apart between administrations.

Also known as: olive oil and chlorophyll

placebo oil

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects \> 60 years old.
• Written informed consent from participants legally authorized representative.
• Subjects who are residing either in an institutionalized setting (e.g. dementia unit, nursing home, assisted living facility, or other residential care facility) or in a non-institutionalized setting where the subject is not living alone and is receiving 24-hour supervision via home health care or a family member. Subjects must have been at their current location for at least 14 days before screening and plan to remain at the same location for the duration of the trial.
• Diagnosis of Dementia (NCD) according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) Criteria for at least 6 months prior to screening.
• Mini-Mental State Examination (MMSE) \< 26.
• Clinically relevant Behavioral and Psychological Symptoms of Dementia (BPSD) operationally defined as NPI-NH agitation/ aggression sub score of ≥3 at screening.
• Documented history of clinically relevant BPSD.
• Ability to participate in study evaluation and ingest oral medication.
• Subjects will be on stable concomitant medications regimen for the treatment of BPSD for at least one month prior to the screening visit.
• Subjects will be on stable concomitant medications regimen for the treatment of concurrent conditions for at least one month prior to the screening visit.

You may not qualify if:

• Patients receiving any of the following medications: Astemizole, Cisapride, Pimozide or Terfenadine.
• The agitation/aggression is attributable to concomitant medications, environmental conditions or psychiatric condition.
• Patients with severe heart disease.
• Subjects suffering from Epilepsy.
• Subjects suffering from anxiety disorder.
• Subjects who had psychiatric condition in the past OR suffering from psychosis.
• Schizophrenia OR family history of Schizophrenia OR any other mental disorder.
• Subjects with any other condition, which in the judgment of the investigator would prevent the subject from completing the study.
• Any condition that the Investigator believes would interfere with the intent of the study or would make participation not in the best interest of the patient.
• Patients suffering from alcohol and/or substance abuse
• Surgery within 30 days prior to screening or scheduled surgery during the study period.

Sponsors & Collaborators

• TO Pharmaceuticals: lead

Study Sites (1)

Laniado Hospital

Netanya, Israel

Location

Related Publications (3)

• Hermush V, Ore L, Stern N, Mizrahi N, Fried M, Krivoshey M, Staghon E, Lederman VE, Bar-Lev Schleider L. Effects of rich cannabidiol oil on behavioral disturbances in patients with dementia: A placebo controlled randomized clinical trial. Front Med (Lausanne). 2022 Sep 6;9:951889. doi: 10.3389/fmed.2022.951889. eCollection 2022.

  PMID: 36148467 DERIVED

• Bosnjak Kuharic D, Markovic D, Brkovic T, Jeric Kegalj M, Rubic Z, Vuica Vukasovic A, Jeroncic A, Puljak L. Cannabinoids for the treatment of dementia. Cochrane Database Syst Rev. 2021 Sep 17;9(9):CD012820. doi: 10.1002/14651858.CD012820.pub2.

  PMID: 34532852 DERIVED

• Solomon HV, Greenstein AP, DeLisi LE. Cannabis Use in Older Adults: A Perspective. Harv Rev Psychiatry. 2021 May-Jun 01;29(3):225-233. doi: 10.1097/HRP.0000000000000289.

  PMID: 33660625 DERIVED

MeSH Terms

Interventions

nabiximols; Olive Oil; Chlorophyll

Intervention Hierarchy (Ancestors)

Dietary Fats, Unsaturated; Dietary Fats; Fats; Lipids; Fats, Unsaturated; Plant Oils; Oils; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Tetrapyrroles; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Vered Hermush, Dr

  Laniado Hospital Geriatric Department

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: A Phase II, Randomized, Double-blind, Placebo-controlled Trial

Study Record Dates

• First Submitted: October 29, 2017
• First Posted: November 1, 2017
• Study Start: December 7, 2017
• Primary Completion: August 18, 2019
• Study Completion: August 18, 2019
• Last Updated: March 8, 2022

Record last verified: 2022-03

Locations

IL (1)