Cannabidiol Medication Intervention Trial

NCT06014424 | Recruiting Phase 2

• 1 other identifier: 3878
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 5

Brief 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.

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline (0 Weeks) to 22 Weeks

Secondary Outcomes (6)

• Behavior - Neuropsychiatric Inventory - Clinician Scale (NPI-C Agitation/NPI-NH)

  Baseline (0 Weeks) to 22 Weeks

• Cognition - Standardized Mini-Mental State Examination (sMMSE)

  Baseline (0 Weeks) to 22 Weeks

• Weight

  Baseline (0 Weeks) to 22 Weeks

• Nutritional Status - Mini Nutritional Assessment - Short Form (MNA-SF)

  Baseline (0 Weeks) to 22 Weeks

• Pain - Pain Assessment Checklist for Seniors with Limited Ability to Communicate - II (PACSLAC-II)

  Baseline (0 Weeks) to 22 Weeks

Other Outcomes (1)

• Sedation - Udvalg for Kliniske Undersøgelser (UKU) Side-Effect Rating Scale

  Baseline (0 Weeks) to 22 Weeks

Study Arms (2)

CBD

EXPERIMENTAL

Participants randomized to the CBD arm will be titrated up to a maximum dose of 800 mg/day

Drug: CBD

Placebo

EXPERIMENTAL

Participants randomized to the placebo will be titrated up to a maximum dose of 800 mg/day

Other: Placebo

Interventions

CBD DRUG

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.

CBD

Placebo OTHER

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.

Placebo

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead
• Weston Brain Institute: collaborator

Study Sites (5)

University of Calgary

Calgary, Alberta, T2N 4N1, Canada

RECRUITING

London Health Sciences Centre

London, Ontario, Canada

RECRUITING

Sunnybrook Health Sciences Centre

Toronto, Ontario, M3H0A7, Canada

RECRUITING

Centre for Addiction and Mental Health

Toronto, Ontario, Canada

RECRUITING

Ontario Shores Centre for Mental Health Sciences

Whitby, Ontario, L1N 5S9, Canada

RECRUITING

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Krista L. Lanctot, PhD

  Sunnybrook Research Institute

  PRINCIPAL INVESTIGATOR

• Giovanni Marotta

  Sunnybrook Health Sciences Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

CALM-IT Coordinating Centre

CONTACT

416-480-6100; CALM-IT@sunnybrook.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: This is a double-blind study. Participants, Subsequent decision maker and investigator will be blinded to the treatment arm. Unblinding will not be allowed unless there are exceptional clinical circumstances that justify it
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2023
• First Posted: August 28, 2023
• Study Start: September 27, 2023
• Primary Completion (Estimated): December 29, 2026
• Study Completion (Estimated): December 29, 2026
• Last Updated: January 29, 2026

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (5)