Cannabidiol Medication Intervention Trial

NCT ID: NCT06014424

Last Updated: 2025-07-11

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-09-27
• Study Completion Date: 2026-12-29

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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

CBD

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

Group Type: EXPERIMENTAL

CBD

Intervention Type: 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.

Placebo

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

Group Type: EXPERIMENTAL

Placebo

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Weston Brain Institute

OTHER

Sponsor Role: collaborator

Sunnybrook Health Sciences Centre

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Krista L. Lanctot, PhD

Role: PRINCIPAL_INVESTIGATOR

Sunnybrook Research Institute

Giovanni Marotta

Role: PRINCIPAL_INVESTIGATOR

Sunnybrook Health Sciences Centre

Locations

University of Calgary

Calgary, Alberta, Canada

Site Status: NOT_YET_RECRUITING

London Health Sciences Centre

London, Ontario, Canada

Site Status: NOT_YET_RECRUITING

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Site Status: RECRUITING

Centre for Addiction and Mental Health

Toronto, Ontario, Canada

Site Status: NOT_YET_RECRUITING

Ontario Shores Centre for Mental Health Sciences

Whitby, Ontario, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

CALM-IT Coordinating Centre

Role: CONTACT

CALM-IT@sunnybrook.ca

416-480-6100 ext. 5630

Facility Contacts

Ramnik Sekhon

Role: primary

ramnik.sekhon@ucalgary.ca

Adriana Diez

Role: primary

Adriana.Diez@lhsc.on.ca

519-685-8500 ext. 77024

Kritleen Bawa

Role: primary

kritleen.bawa@sri.utoronto.ca

416-480-6100 ext. 63185

Brigette Mayorga

Role: primary

Brigette.Mayorga@camh.ca

Elaina Niciforos

Role: primary

niciforose@ontarioshores.ca

Other Identifiers

3878

Identifier Type: -

Identifier Source: org_study_id