Alzheimer DiseasePhase 2CALM-ITNCT06014424
Cannabidiol Medication Intervention Trial
A Phase 2 study testing CBD in people with Alzheimer Disease, run by Sunnybrook Health Sciences Centre at 5 sites in Canada.
Trial summary
CALM-IT is a Randomized, double-blind, placebo-controlled cross-over clinical trial. Safety and efficacy of cannabidiol (CBD) capsules assessed for managing agitation in patients with AD and to identify novel biomarkers of agitation severity and treatment response. Read more about this study
- Who is it for?
- Ages 55 years and older
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- CBD
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 5 sitesCanada
- Study dates
- 27 Sep 2023to 29 Dec 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 55 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males or females ≥55 years of age; female must be post-menopausal or must agree to comply with contraception requirements. Males should also abide by contraceptive requirements when the partner is a woman of childbearing potential. Acceptable methods of contraception include: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, which may be oral, intravaginal, or transdermal; progestogen-only hormonal contraception associated with inhibition of ovulation, which may be oral, injectable, or implantable; intrauterine device or intrauterine hormone-releasing system; vasectomy of a female subject's male partner (with medical assessment and confirmation of vasectomy surgical success); bilateral tubal occlusion
- Diagnostic and Statistical Manual of Mental Disorders-5 (DSM 5) criteria for Major Neurocognitive Disorder due to possible AD. Patients with Major Neurocognitive Disorder due to multiple etiologies (AD and vascular) will be included
- sMMSE ≤24
- Presence of clinically significant agitation based on the IPA definition at both screening and baseline
- If treated with cognitive-enhancing medications (cholinesterase inhibitors and/or memantine), dosage must be stable for at least 3 months prior to study randomization
- Availability of a primary caregiver to accompany the participant to study visits and to participate in the study. The primary caregiver must be sufficiently proficient in English to complete the required study assessments, as per investigator judgement and should spend at least 10 hours a week with the participant
- Willing and able to provide informed consent and/or have a Substitute Decision Maker (SDM) provide informed consent on behalf of the participant
Who cannot join
- Change in psychotropic medications less than the duration of 5 half-lives of the medication in question prior to screening (e.g., concomitant antidepressants or atypical antipsychotics) and any changes during study participation
- Contraindications to CBs, e.g. allergies to cannabis and cannabis products, potential clinically important drug-drug interactions (e.g. strong CYP3A4 inducers/inhibitors, anticonvulsants)
- Vascular disease, clinically important cerebrovascular disease or current uncontrolled cardiovascular disease (e.g. uncontrolled hypertension, ischemic heart disease, arrhythmia and severe heart failure, cardiovascular accident in the 3 months prior to Screening (V1)), as per investigator assessment
- Clinically significant liver disease, as reflected by serum alanine aminotransferase or aspartate aminotransferase > 2 x upper limit of normal (ULN), or total bilirubin > 1.5 x ULN; The Investigator may decide to repeat the assessment to confirm criterion prior to screen failing the participant
- Clinically significant impaired renal function at screening, as per investigator assessment
- Currently meeting DSM 5 criteria for Major Depressive Episode Presence, or current substance dependence (excluding caffeine and nicotine) or history of other major psychiatric disorders or neurological conditions (e.g. psychotic disorders, schizophrenia, stroke, epilepsy)
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- Substance-Related Disorders (excluding caffeine and nicotine)
- Clinically significant delusions and/or hallucinations (e.g. NPI-NH delusion/hallucinations subscore ≥4 or judgement of QI)
- Reported use of marijuana or cannabinoid-based medications, products or supplements (botanical or synthetic) within 1 week prior to randomization
- Systolic blood pressure (SBP) < 90 mmHg or > 150 mmHg or diastolic blood pressure (DBP) < 50mmHg or > 105 mmHg at screening or baseline (prior to randomization) or a postural drop in SBP ≥ 20 mmHg or DBP ≥ 10 mmHg at screening
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
Canada5 sites, 5 recruiting
- Recruiting
University of Calgary
Calgary, Alberta, T2N 4N1
Ramnik Sekhon, ramnik.sekhon@ucalgary.ca
- Recruiting
London Health Sciences Centre
London, Ontario
Adriana Diez, 519-685-8500 ext. 77024, Adriana.Diez@lhsc.on.ca
- Recruiting
Sunnybrook Health Sciences Centre
Toronto, Ontario, M3H0A7
Kate Survilla, 416-480-6100 ext. 63185, kate.survilla@sri.utoronto.ca
Krista Lanctot
- Recruiting
Centre for Addiction and Mental Health
Toronto, Ontario
Brigette Mayorga, Brigette.Mayorga@camh.ca
- Recruiting
Ontario Shores Centre for Mental Health Sciences
Whitby, Ontario, L1N 5S9
Heather Daly, dalyh@ontarioshores.ca
About this study
Official title: Cannabidiol Medication Intervention Trial (CALM-IT)
CALM-IT is a Randomized, double-blind, placebo-controlled cross-over clinical trial. Safety and efficacy of cannabidiol (CBD) capsules assessed for managing agitation in patients with AD and to identify novel biomarkers of agitation severity and treatment response.
Read the detailed description
This study will look at whether CBD is an effective treatment for agitation in Alzheimer's disease (AD). This naturally derived CBD is highly pure (99%) and made by a manufacturer who meets Health Canada guidelines Cannabis products are legal for purchase in Canada.
Agitation is common in AD and is known to correlate with physical health problems such as falls and weight loss, AD progression, and caregiver burden. Current treatments for agitation in AD are not beneficial for everyone and there are concerns regarding their safety. Treating agitation is important in improving the quality of life of AD patients and their families and there is a need to identify safer and more effective treatments for agitation in AD.
The structure of this trial is called a "cross-over study". Participants will be randomized to receive either CBD or placebo during the first of two treatment phases. They will then cross-over to the opposite treatment during the second treatment phase. Participants will be on the study treatment for a total of 19 weeks and then will be followed for 4 more weeks after finishing the study treatment. There will be 12 study visits approximately every 2 weeks and 8 telephone visits every week during the study.
In addition to looking at the effectiveness of CBD in treating agitation, the researchers will also look at whether it is beneficial for other relevant outcomes for patients with AD including overall neuropsychiatric symptoms, caregiver distress, cognition, nutritional status, and pain.
- Conditions
- Alzheimer Disease
- Being tested
- CBD, Placebo
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CBDDrug
Participants in this arm will receive CBD for 8 weeks during the first treatment period. They will then receive a two-week single-blind placebo washout before moving into the second 8-week treatment period, during which they will receive the opposite study treatment than the one given in the first treatment period.
PlaceboOther
Participants in this arm will receive placebo for 8 weeks during the first treatment period. They will then receive a two-week single-blind placebo washout before moving into the second 8-week treatment period, during which they will receive the opposite study treatment than the one given in the first treatment period.
| Study group | Role | What they receive |
|---|---|---|
| CBD | Experimental | Participants randomized to the CBD arm will be titrated up to a maximum dose of 800 mg/day Receives: Drug: CBD |
| Placebo | Experimental | Participants randomized to the placebo will be titrated up to a maximum dose of 800 mg/day Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Agitation - Cohen-Mansfield Agitation Inventory (CMAI)
A 29-point scale that measures agitation in two dimensions, verbal and physical, each of which having two poles, aggressive and on-aggressive. Scores range from 29-203 points, with a higher score indicating a worse outcome.
Measured: Baseline (0 Weeks) to 22 Weeks
Secondary outcomes (6)
Behavior - Neuropsychiatric Inventory - Clinician Scale (NPI-C Agitation/NPI-NH)
NPI-C agitation is a widely used assessment of behaviour disturbances in dementia, including: apathy agitation, delusions, hallucinations, depression, euphoria, aberrant motor behaviour, irritability, disinhibition, anxiety, sleeping, and eating. NPI-NH is a caregiver-rated scale that is widely used to assess behavioral disturbances in dementia as well as caregiver distress. These behaviours include: delusions, hallucinations, agitation, aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, aberrant motor behavior, sleep, appetite and eating disorders, and aberrant vocalizations. The frequency and severity of these symptoms are judged on a 4-point and 3-point scale, respectively. Scores range from 0-144 points, with a higher score indicating a worse outcome.
Measured: Baseline (0 Weeks) to 22 Weeks
Cognition - Standardized Mini-Mental State Examination (sMMSE)
Measures global cognition, and assesses orientation to time and place, immediate recall, short-term verbal memory, calculation, language, and construct ability. Scores range from 0-30 points, with a lower score indicating a worse outcome.
Measured: Baseline (0 Weeks) to 22 Weeks
Weight
Weight will be collected in kilograms. A change of 7% in weight will be considered clinically significant change.
Measured: Baseline (0 Weeks) to 22 Weeks
Nutritional Status - Mini Nutritional Assessment - Short Form (MNA-SF)
A structured interview consisting of 6 items that categorizes patients as malnourished, at risk of malnutrition, or of normal nutritional status. Scores range from 0-14 points, with a lower score indicating a worse outcome.
Measured: Baseline (0 Weeks) to 22 Weeks
Pain - Pain Assessment Checklist for Seniors with Limited Ability to Communicate - II (PACSLAC-II)
A 31-item observer-rated scale assessing facial expressions, activity/body movements, social/personality/mood indicators and mental status changes. Scores range form 0-31 points, with a higher score indicating a worse outcome.
Measured: Baseline (0 Weeks) to 22 Weeks
Global Change - Alzheimer's Disease Cooperative Study - Clinical Global Impression of Severity/Change (ADCS-CGIS/C)
A commonly-used clinician-rated scale that quantifies disease severity and clinical change (worsening, no change, or improvement), based on information regarding the patient's medical history, cognition, behaviour, and function. Scores range from 1-7, with a lower score indicating a worse outcome.
Measured: Baseline (0 Weeks) to 22 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2023
- Study start27 Sep 2023
- Primary completion29 Dec 2026 (estimated)
- Study completion29 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by Sunnybrook Health Sciences CentreThe sponsor's other registered studies.
- 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
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sunnybrook Health Sciences Centre
- Sponsor type
- University, hospital or other
- Collaborators
- Weston Brain Institute
- Responsible party
- Sponsor
- Investigators
- Krista L. Lanctot, PhD, Principal investigator, Sunnybrook Research InstituteGiovanni Marotta, Principal investigator, Sunnybrook Health Sciences Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06014424
- Sponsor's protocol ID
- 3878
- Acronym
- CALM-IT
- Status last verified
- Jul 2026
- First submitted
- 24 Jul 2023
- Last updated
- 31 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cannabidiol Medication Intervention Trial (CALM-IT)
- ClinicalTrials.gov ID
- NCT06014424
- Acronym / sponsor ID
- CALM-IT / 3878
- Conditions
- Alzheimer Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Sunnybrook Health Sciences CentreUniversity, hospital or other
- Collaborators
- Weston Brain Institute
- Study start
- 27 Sep 2023 (actual)
- Primary completion
- 29 Dec 2026 (estimated)
- Study completion
- 29 Dec 2026 (estimated)
- First posted
- 28 Aug 2023 (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.
CALM-IT is a Randomized, double-blind, placebo-controlled cross-over clinical trial. Safety and efficacy of cannabidiol (CBD) capsules assessed for managing agitation in patients with AD and to identify novel biomarkers of agitation severity and treatment response.
Detailed description
This study will look at whether CBD is an effective treatment for agitation in Alzheimer's disease (AD). This naturally derived CBD is highly pure (99%) and made by a manufacturer who meets Health Canada guidelines Cannabis products are legal for purchase in Canada.
Agitation is common in AD and is known to correlate with physical health problems such as falls and weight loss, AD progression, and caregiver burden. Current treatments for agitation in AD are not beneficial for everyone and there are concerns regarding their safety. Treating agitation is important in improving the quality of life of AD patients and their families and there is a need to identify safer and more effective treatments for agitation in AD.
The structure of this trial is called a "cross-over study". Participants will be randomized to receive either CBD or placebo during the first of two treatment phases. They will then cross-over to the opposite treatment during the second treatment phase. Participants will be on the study treatment for a total of 19 weeks and then will be followed for 4 more weeks after finishing the study treatment. There will be 12 study visits approximately every 2 weeks and 8 telephone visits every week during the study.
In addition to looking at the effectiveness of CBD in treating agitation, the researchers will also look at whether it is beneficial for other relevant outcomes for patients with AD including overall neuropsychiatric symptoms, caregiver distress, cognition, nutritional status, and pain.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CBD | Experimental | Drug: CBDParticipants randomized to the CBD arm will be titrated up to a maximum dose of 800 mg/day |
| Placebo | Experimental | Other: PlaceboParticipants randomized to the placebo will be titrated up to a maximum dose of 800 mg/day |
Who may qualify
- Ages
- 55 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Males or females ≥55 years of age; female must be post-menopausal or must agree to comply with contraception requirements. Males should also abide by contraceptive requirements when the partner is a woman of childbearing potential. Acceptable methods of contraception include: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, which may be oral, intravaginal, or transdermal; progestogen-only hormonal contraception associated with inhibition of ovulation, which may be oral, injectable, or implantable; intrauterine device or intrauterine hormone-releasing system; vasectomy of a female subject's male partner (with medical assessment and confirmation of vasectomy surgical success); bilateral tubal occlusion
- Diagnostic and Statistical Manual of Mental Disorders-5 (DSM 5) criteria for Major Neurocognitive Disorder due to possible AD. Patients with Major Neurocognitive Disorder due to multiple etiologies (AD and vascular) will be included
- sMMSE ≤24
- Presence of clinically significant agitation based on the IPA definition at both screening and baseline
- If treated with cognitive-enhancing medications (cholinesterase inhibitors and/or memantine), dosage must be stable for at least 3 months prior to study randomization
Key exclusion criteria (10 listed)
- Change in psychotropic medications less than the duration of 5 half-lives of the medication in question prior to screening (e.g., concomitant antidepressants or atypical antipsychotics) and any changes during study participation
- Contraindications to CBs, e.g. allergies to cannabis and cannabis products, potential clinically important drug-drug interactions (e.g. strong CYP3A4 inducers/inhibitors, anticonvulsants)
- Vascular disease, clinically important cerebrovascular disease or current uncontrolled cardiovascular disease (e.g. uncontrolled hypertension, ischemic heart disease, arrhythmia and severe heart failure, cardiovascular accident in the 3 months prior to Screening (V1)), as per investigator assessment
- Clinically significant liver disease, as reflected by serum alanine aminotransferase or aspartate aminotransferase > 2 x upper limit of normal (ULN), or total bilirubin > 1.5 x ULN; The Investigator may decide to repeat the assessment to confirm criterion prior to screen failing the participant
- Clinically significant impaired renal function at screening, as per investigator assessment
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 |
|---|---|---|
| CBDParticipants in this arm will receive CBD for 8 weeks during the first treatment period. They will then receive a two-week single-blind placebo washout before moving into the second 8-week treatment period, during which they will receive the opposite study treatment than the one given in the first treatment period. | Drug | CBD |
| PlaceboParticipants in this arm will receive placebo for 8 weeks during the first treatment period. They will then receive a two-week single-blind placebo washout before moving into the second 8-week treatment period, during which they will receive the opposite study treatment than the one given in the first treatment period. | Other | Placebo |
Primary outcome
Agitation - Cohen-Mansfield Agitation Inventory (CMAI)
Time frame: Baseline (0 Weeks) to 22 Weeks
A 29-point scale that measures agitation in two dimensions, verbal and physical, each of which having two poles, aggressive and on-aggressive. Scores range from 29-203 points, with a higher score indicating a worse outcome.
6 secondary outcomes
Behavior - Neuropsychiatric Inventory - Clinician Scale (NPI-C Agitation/NPI-NH)
Time frame: Baseline (0 Weeks) to 22 Weeks
Cognition - Standardized Mini-Mental State Examination (sMMSE)
Time frame: Baseline (0 Weeks) to 22 Weeks
Weight
Time frame: Baseline (0 Weeks) to 22 Weeks
Nutritional Status - Mini Nutritional Assessment - Short Form (MNA-SF)
Time frame: Baseline (0 Weeks) to 22 Weeks
Pain - Pain Assessment Checklist for Seniors with Limited Ability to Communicate - II (PACSLAC-II)
Time frame: Baseline (0 Weeks) to 22 Weeks
Global Change - Alzheimer's Disease Cooperative Study - Clinical Global Impression of Severity/Change (ADCS-CGIS/C)
Time frame: Baseline (0 Weeks) to 22 Weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2026.
- Individual participant dataSharing planned: No
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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.
Krista L. Lanctot, PhD principal investigator
Sunnybrook Research Institute
Giovanni Marotta principal investigator
Sunnybrook Health Sciences Centre
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CBD in people with Alzheimer Disease, run by Sunnybrook Health Sciences Centre at 5 sites in Canada.
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 7 inclusion and 10 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: looking for participants now, as of the sponsor's last update on 31 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Canada. 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. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact CALM-IT Coordinating Centre (416-480-6100 ext. 5630, CALM-IT@sunnybrook.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Agitation - Cohen-Mansfield Agitation Inventory (CMAI) (time frame: Baseline (0 Weeks) to 22 Weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 31 Jul 2026.