Cannabidiol Medication Intervention Trial (CALM-IT)

January 27, 2026 updated by: Sunnybrook Health Sciences Centre

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

40

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Canada
    • Alberta
    • Ontario
      • London, Ontario, Canada
        • Recruiting
        • London Health Sciences Centre
        • Contact:
      • Toronto, Ontario, Canada
      • Toronto, Ontario, Canada, M3H0A7
        • Recruiting
        • Sunnybrook Health Sciences Centre
        • Principal Investigator:
          • Krista Lanctot
        • Contact:
      • Whitby, Ontario, Canada, L1N 5S9
        • Recruiting
        • Ontario Shores Centre for Mental Health Sciences
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. 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
  2. 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
  3. sMMSE ≤24
  4. Presence of clinically significant agitation based on the IPA definition at both screening and baseline
  5. If treated with cognitive-enhancing medications (cholinesterase inhibitors and/or memantine), dosage must be stable for at least 3 months prior to study randomization
  6. 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
  7. Willing and able to provide informed consent and/or have a Substitute Decision Maker (SDM) provide informed consent on behalf of the participant

Exclusion Criteria:

  1. 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
  2. Contraindications to CBs, e.g. allergies to cannabis and cannabis products, potential clinically important drug-drug interactions (e.g. strong CYP3A4 inducers/inhibitors, anticonvulsants)
  3. 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
  4. 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
  5. Clinically significant impaired renal function at screening, as per investigator assessment
  6. 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)
  7. Substance-Related Disorders (excluding caffeine and nicotine)
  8. Clinically significant delusions and/or hallucinations (e.g. NPI-NH delusion/hallucinations subscore ≥4 or judgement of QI)
  9. Reported use of marijuana or cannabinoid-based medications, products or supplements (botanical or synthetic) within 1 week prior to randomization
  10. 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: CBD
Participants randomized to the CBD arm will be titrated up to a maximum dose of 800 mg/day
Drug: CBD
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.
Experimental: Placebo
Participants randomized to the placebo will be titrated up to a maximum dose of 800 mg/day
Other: Placebo
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline (0 Weeks) to 22 Weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cognition - Standardized Mini-Mental State Examination (sMMSE)
Time Frame: Baseline (0 Weeks) to 22 Weeks
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.
Baseline (0 Weeks) to 22 Weeks
Weight
Time Frame: Baseline (0 Weeks) to 22 Weeks
Weight will be collected in kilograms. A change of 7% in weight will be considered clinically significant change.
Baseline (0 Weeks) to 22 Weeks
Nutritional Status - Mini Nutritional Assessment - Short Form (MNA-SF)
Time Frame: Baseline (0 Weeks) to 22 Weeks
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.
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
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.
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
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.
Baseline (0 Weeks) to 22 Weeks
Behavior - Neuropsychiatric Inventory - Clinician Scale (NPI-C Agitation/NPI-NH)
Time Frame: Baseline (0 Weeks) to 22 Weeks
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.
Baseline (0 Weeks) to 22 Weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sedation - Udvalg for Kliniske Undersøgelser (UKU) Side-Effect Rating Scale
Time Frame: Baseline (0 Weeks) to 22 Weeks
Sedation will be measured using the Sleepiness/Sedation subscale of the UKU-Side Effect Rating Scale. The UKU is a clinician-rated scale that assesses the side effects psychopharmacological medications. Scores range from 0-3, with a higher score indicating more sleepiness/sedation.
Baseline (0 Weeks) to 22 Weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sunnybrook Health Sciences Centre

Collaborators

Weston Brain Institute

Investigators

  • Principal Investigator: Krista L. Lanctot, PhD, Sunnybrook Research Institute
  • Principal Investigator: Giovanni Marotta, Sunnybrook Health Sciences Centre

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 27, 2023

Primary Completion (Estimated)

December 29, 2026

Study Completion (Estimated)

December 29, 2026

Study Registration Dates

First Submitted

July 24, 2023

First Submitted That Met QC Criteria

August 22, 2023

First Posted (Actual)

August 28, 2023

Study Record Updates

Last Update Posted (Actual)

January 29, 2026

Last Update Submitted That Met QC Criteria

January 27, 2026

Last Verified

April 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 3878

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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