CALM-IT: Cannabinoid Liquid Medication Intervention Trial
Study Details
Study Description
Brief Summary
CALM-IT is a Randomized, double-blind, placebo-controlled cross-over clinical trial. Safety and efficacy of JZP541 assessed for managing agitation in patients with AD and to identify novel biomarkers of agitation severity and treatment response.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
This study will look at whether JZP541 is an effective treatment for agitation in Alzheimer's disease (AD). JZP541 is a botanical cannabinoid drug product containing cannabidiol (CBD), cannabichrome (CBC) and delta-9-tetrahydrocannabinol (THC), amongst other cannabinoid and noncannabinoid plant-derived components. 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 JZP541 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 JZP541 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
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: JZP541 then Placebo Participants in this arm will receive JZP541 for 8 weeks. Visits will occur every 2 weeks for 8 weeks during the first treatment period, which will be followed by a two-week single-blind placebo washout. Participants will then receive the placebo for another 8 weeks. |
Drug: JZP541
ZP541 is a complex botanical drug product containing cannabidiol (CBD), cannabichrome (CBC) and delta-9-tetrahydrocannabinol (THC), amongst other cannabinoid and noncannabinoid plant-derived components.
|
| Experimental: Placebo then JZP541 Participants in this arm will receive placebo for 8 weeks. Visits will occur every 2 weeks for 8 weeks during the first treatment period, which will be followed by a two-week single-blind placebo washout. Participants will then receive JZP541 for another 8 weeks. |
Drug: JZP541
ZP541 is a complex botanical drug product containing cannabidiol (CBD), cannabichrome (CBC) and delta-9-tetrahydrocannabinol (THC), amongst other cannabinoid and noncannabinoid plant-derived components.
|
Outcome Measures
Primary Outcome Measures
- Agitation - Cohen-Mansfield Agitation Inventory (CMAI) [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.
Secondary Outcome Measures
- Behaviour - Neuropsychiatric Inventory - Clinician Scale (NPI-C) [Baseline (0 Weeks) to 22 Weeks]
A widely used assessment of behaviour disturbances in dementia, including: apathy agitation, delusions, hallucinations, depression, euphoria, abeerant motor behaviour, irritability, disinhibition, anxiety, sleeping, and eating. 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.
- Cognition - Standardized Mini-Mental State Examination (sMMSE) [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.
- Weight [Baseline (0 Weeks) to 22 Weeks]
Weight will be collected in kilograms. A change of 7% in weight will be considered clinically significant change.
- Nutritional Status - Mini Nutritional Assessment - Short Form (MNA-SF) [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.
- Pain - Pain Assessment Checklist for Seniors with Limited Ability to Communicate - II (PACSLAC-II) [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.
- Global Change - Alzheimer's Disease Cooperative Study - Clinical Global Impression of Severity/Change (ADCS-CGIS/C) [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. Numerical scores are not assigned.
Other Outcome Measures
- Sedation - Udvalg for Kliniske Undersøgelser (UKU) Side-Effect Rating Scale [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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
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
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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
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sMMSE ≤24
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Presence of clinically significant agitation based on the IPA definition at both screening and baseline
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If treated with cognitive-enhancing medications (cholinesterase inhibitors and/or memantine), dosage must be stable for at least 3 months prior to study randomization
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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
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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:
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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
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Administration of strong inducers of CYP3A4 ≤ 14 days prior to first doses of study intervention or have ongoing requirements for these medications
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Use of anticonvulsant medications
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Contraindications to CBs, e.g. allergies to cannabis and cannabis products, potential clinically important drug-drug interactions
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Any type of arterial vascular disease, cerebrovascular disease and current uncontrolled cardiovascular disease (e.g. uncontrolled hypertension, ischemic heart disease, arrhythmia and severe heart failure), as per investigator assessment
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Patients with Cardiovascular Accident in the 3 months prior to Screening (V1)
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Impaired hepatic function, as reflected by serum alanine aminotransferase or aspartate aminotransferase > 2 × upper limit of normal (ULN), or total bilirubin > 1.5
× ULN; the Investigator may decide to repeat the assessment to confirm criterion prior to screen failing the participant
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Presence of clinically significant impaired renal function at screening, as evidenced by an estimated creatinine clearance < 30 mL/min/1.73 m2 (as calculated by the glomerular filtration rate using the Modification of Diet in Renal Disease study equation)
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Presence or history of other psychiatric disorders or neurological conditions (e.g.
psychotic disorders, schizophrenia, stroke, epilepsy) and known or suspected psychotic disorder in a first degree relative
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Participants currently meeting DSM 5 criteria for Major Depressive Episode
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History of suicidal behavior or suicidal ideation of type 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS)
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Current substance dependence (excluding caffeine and nicotine)
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Clinically significant delusions and/or hallucinations (NPI-C delusion/hallucinations subscore ≥4)
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Reported use of marijuana or cannabinoid-based medications, products or supplements (botanical or synthetic) within 1 week prior to randomization
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Systolic blood pressure (SBP) < 90 mmHg or > 150 mmHg or diastolic blood pressure (DBP) < 50 mmHg or > 105 mmHg at screening or baseline (prior to randomization) or a postural drop in SBP ≥ 20 mmHg or DBP ≥ 10 mmHg at screening
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QT Interval Corrected Using Fridericia's Formula > 450 ms (confirmed by 2 consecutive electrocardiograms (ECGs) or a history of additional risk factors for Torsades de Pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Calgary | Calgary | Alberta | Canada | T2N 4N1 |
| 2 | Sunnybrook Health Sciences Centre | Toronto | Ontario | Canada | M3H0A7 |
| 3 | Ontario Shores Centre for Mental Health Sciences | Whitby | Ontario | Canada | L1N 5S9 |
Sponsors and Collaborators
- Sunnybrook Health Sciences Centre
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 3878