Agitation Related to DementiaPhase 2NCT03328676
The Effect of Cannabis on Dementia Related Agitation and Aggression
A Phase 2 study testing Cannabis in people with Agitation Related to Dementia, run by TO Pharmaceuticals at 1 site in Israel.
Trial 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. Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Agitation Related to Dementia
- What is being tested?
- Cannabis
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 64 participants
- Where
- 1 siteIsrael
- Study dates
- 7 Dec 2017to 18 Aug 2019
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase II, Randomized, Double-blind, Placebo-controlled Trial to Investigate the Efficacy and Safety of Avidekel Oil for the Treatment of Subjects With Agitation Related to Dementia
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.
Read the detailed description
In this randomized, double-blind placebo-controlled trial, 60 patients will be randomly assigned to receive either CBD-A (30:1) cannabis rich low THC oil (30% CBD and 1% THC) or a placebo oil. The primary efficacy endpoint was a decrease of four or more points on the Cohen-Mansfield Agitation Inventory (CMAI) score by week 16, as compared to baseline. Secondary endpoints included improvement of other neurobehavioral symptoms.
The following questionnaires will be administered by trained staff at every visit: The CMAI, a to measure the types and frequencies of agitated behaviors, and the Neuropsychiatric Inventory-Nursing Home Version (NPI-NH) to measure behavioral disturbances.
- Conditions
- Agitation Related to Dementia
- Being tested
- Cannabis, Placebo oil
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CannabisDrug
Also called CBD-A
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.
Placebo oilDrug
Also called olive oil and chlorophyll
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.
| Study group | Role | What they receive |
|---|---|---|
| "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. Receives: Drug: Cannabis |
| placebo oil | Placebo comparator | Patients in the control group will receive placebo. Receives: Drug: Placebo oil |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: week 16
Secondary outcomes (1)
Change in score of Neuropsychiatric Inventory-Nursing Home Version (NPI-NH)
Proportion of subjects with change in score of Neuropsychiatric Inventory-Nursing Home Version (NPI-NH). The greater the NPI-NH score, the more severe and frequent the behavioral disturbances
Measured: week 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2017
- Study start7 Dec 2017
- Primary completion18 Aug 2019
- Study completion18 Aug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Agitation Related to DementiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A Phase II, Randomized, Double-blind, Placebo-controlled Trial
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- TO Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Vered Hermush, Dr, Principal investigator, Laniado Hospital Geriatric Department
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03328676
- Sponsor's protocol ID
- TO_D02_2016
- Status last verified
- Mar 2022
- First submitted
- 29 Oct 2017
- Last updated
- 8 Mar 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 36148467Bosnjak 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.
PubMed 34532852Solomon 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.
PubMed 33660625
Study at a glance
From the registry record, last updated by the sponsor on 8 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Randomized, Double-blind, Placebo-controlled Trial to Investigate the Efficacy and Safety of Avidekel Oil for the Treatment of Subjects With Agitation Related to Dementia
- ClinicalTrials.gov ID
- NCT03328676
- Acronym / sponsor ID
- TO_D02_2016
- Conditions
- Agitation Related to Dementia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- TO PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 7 Dec 2017 (actual)
- Primary completion
- 18 Aug 2019 (actual)
- Study completion
- 18 Aug 2019 (actual)
- First posted
- 1 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
In this randomized, double-blind placebo-controlled trial, 60 patients will be randomly assigned to receive either CBD-A (30:1) cannabis rich low THC oil (30% CBD and 1% THC) or a placebo oil. The primary efficacy endpoint was a decrease of four or more points on the Cohen-Mansfield Agitation Inventory (CMAI) score by week 16, as compared to baseline. Secondary endpoints included improvement of other neurobehavioral symptoms.
The following questionnaires will be administered by trained staff at every visit: The CMAI, a to measure the types and frequencies of agitated behaviors, and the Neuropsychiatric Inventory-Nursing Home Version (NPI-NH) to measure behavioral disturbances.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- A Phase II, Randomized, Double-blind, Placebo-controlled Trial
| Arm | Type | Receives |
|---|---|---|
| "Avidekel " cannabis oil 20:1 CBD:THC | Experimental | Drug: CannabisThe 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. |
| placebo oil | Placebo comparator | Drug: Placebo oilPatients in the control group will receive placebo. |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CannabisAlso: CBD-APatients 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. | Drug | "Avidekel " cannabis oil 20:1 CBD:THC |
| Placebo oilAlso: olive oil and chlorophyllPatients 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. | Drug | placebo oil |
Primary outcome
Change in score of Cohen-Mansfield Agitation Inventory (CMAI)
Time frame: week 16
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.
1 secondary outcome
Change in score of Neuropsychiatric Inventory-Nursing Home Version (NPI-NH)
Time frame: week 16
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2022.
- Derived from this study: PubMed 36148467Hermush 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.
- Derived from this study: PubMed 34532852Bosnjak 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.
- Derived from this study: PubMed 33660625Solomon 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vered Hermush, Dr principal investigator
Laniado Hospital Geriatric Department
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cannabis in people with Agitation Related to Dementia, run by TO Pharmaceuticals at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in score of Cohen-Mansfield Agitation Inventory (CMAI) (time frame: week 16). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03328676, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Mar 2022.