Dementia Mental and Behavioural Disorders Dementia
Conditions
Interventions
Trial design overview:
We propose a double-blind, parallel-group, randomised, placebo-controlled trial (RCT) of Sativex® versus placebo to reduce Agitation and aggression symptoms in Alzheimer's Disea
or TAU + Sativex® for 4 weeks. We plan to recruit 60 patients, and randomisation will be in a 1:1 ratio.
Participants will follow the following regimen for Sativex® [2.7mg (THC)/2.5mg (CBD) per spray
Sponsors
King's College London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 24/05/2022: 1. Age 55 - 95 years 2. Probable Alzheimer’s Disease diagnosis according to the criteria of National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDSADRDA) 3. Clinically significant A/A that requires treatment, defined by CMAI >/= 45 and/or NPI-NH Agitation total score >/= 4 4. Residential within a nursing home at recruitment to the study with a history of at least 2 weeks behavioural disturbance 5. Written and witnessed informed consent from participant (if deemed having mental capacity), or from personal legal representative (next of kin/power of attorney), or from professional legal representative (non R/F member who can attest to knowing prospective participant for significant period of time). Informed consent will be sought in this order from these potential sources _____ Previous inclusion criteria: 1. Age 55 - 90 years 2. Probable Alzheimer’s Disease diagnosis according to the criteria of National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDSADRDA) 3. Clinically significant A/A that requires treatment, defined by CMAI >/= 45 and/or NPI-NH Agitation total score >/= 4 4. Residential within a nursing home at recruitment to the study with a history of at least 2 weeks behavioural disturbance 5. Written and witnessed informed consent from participant (if deemed having mental capacity), or from personal legal representative (next of kin/power of attorney), or from professional legal representative (non R/F member who can attest to knowing prospective participant for significant period of time). Informed consent will be sought in this order from these potential sources
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 24/05/2022: 1. Anti-psychotic, anti-epileptic, antidepressant, benzodiazepine, lithium or hypnotic dosage alteration in the 2 weeks prior to the start of the study (and must be expected to maintain dosage throughout study). 2. ChEIs (donepezil, rivastigmine or galantamine) and/or memantine, dosage alteration in the 6 weeks prior to the start of the study. 3. Currently using cannabis-based medicine(s) (defined as being a UK licensed product prescribed by a doctor) 4. Concomitant treatment with strong enzyme inducers (rifampicin, carbamazepine, phenytoin, phenobarbital, St John’s Wort) and/or CYP3A4 inhibitors 5. Hypersensitivity to Sativex® or any of the excipients in the formulation (ethanol anhydrous, 6. Propylene glycol, peppermint oil). 7. Severe cardiovascular disease, recent myocardial infarction (‘recency’ determined by study doctor according to clinical significance), uncompensated congestive heart failure and uncontrolled hypertension. 8. QT interval by Fredericia (QTcF) greater than 450 will be excluded if ECG conducted 9. Severe, unstable or poorly controlled medical illness. 10. If diagnosed with severe kidney disease/impairment (as deemed by study doctor/PI), a blood test (taken within 12 months) is required to assess severity of renal impairment: Renal Impairment is defined by estimated Glomerular Filtration Rate (eGFR) less than 45ml/min 11. If diagnosed with severe liver disease/impairment (as deemed by study doctor/PI), a blood test (taken within 12 months) is required to assess severity of hepatic impairment: Hepatic impairment is defined by Alanine aminotransferase (ALT)/ Aspartate aminotransferase (AST) levels 3 times greater than reference value of laboratory (165 IU/L+ for ALT; 150 IU/L+ for AST) 12. Any disability that may interfere with the patient completing the study procedure. 13. History or family history of schizophrenia, or other psychotic illness; history of severe personality disorder or other significant psychiatric disorder other than depression associated with their underlying condition. 14. Delirium, pain or any medical illness as a clear cause of agitation 15. Females of child-bearing potential, defined as ‘having experienced menarche and are not permanently sterilised (e.g. by hysterectomy, bilateral salpingectomy and bilateral oophorectomy) or post-menopausal (defined as at least 1 year since last regular menstrual period)’. 16. Evidence of ‘suicidality risk’ determined by >0 on Columbia-Suicide Severity Rating Scale (CSSRS) 17. History/current seizure disorder 18. History/current of alcohol or other substance abuse 19. History of fall(s) within the last 6 months _____ Previous exclusion criteria: 1. Anti-psychotic, anti-epileptic, antidepressant, benzodiazepine, lithium or hypnotic dosage alteration in the 2 weeks prior to the start of the study (and must maintain dosage throughout study) 2. ChEIs (donepezil, rivastigmine or galantamine) and/or memantine, dosage alteration in the 6 weeks prior to the start of the study 3. Currently using cannabis-based medicine(s) (defined as being a UK licensed product prescribed by a doctor) 4. Concomitant treatment with strong enzyme inducers (rifampicin, carbamazepine, phenytoin, phenobarbital, St Johns Wort) and/or CYP3A4 inhibitors 5. Hypersensitivity to Sativex® or any of the excipients in the formulation (ethanol anhydrous, Propylene glycol, peppermint oil) 6. Severe cardiovascular disease, recent myocardial infarction
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Feasibility outcome measures: 1. Number of participants recruited measured using case report forms at the end of the study 2. Number of participants followed up measured using case report forms at the end of the study 3. Medication adherence measured using case report forms at the end of the study | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Safety and tolerability: 1.1. Tolerability: Assessed by self- & carer-report of side-effects, medication discontinuation, Co-prescribed psychotropic medications, and number of occasions rescue treatment utilised throughout the study 1.2. Safety parameters: 1.2.1. Blood samples for Haematology (Full red & white blood cell count and Haemoglobin) and Biochemistry (Urea, liver function test, thyroid function test, lipid profile) measured at baseline and 4 weeks 1.2.2. Vital signs: Heart rate and Blood pressure; Physical examination measured at baseline and 4 weeks 1.2.3. Follow up phone calls for self-reported side effects, including incidence of falls and compliance (week 2 and 6) 2. Neuropsychiatric symptoms, cognition, pain, quality of life measured at baseline and again where indicated: 2.1. Cohen-Mansfield Agitation Inventory (CMAI) at 2, 4 & 8 weeks at daily dose 2.2. Neuropsychiatric Inventory – Nursing Home (NPI-NH) 2, 4 & 8 weeks 2.3. Mini Mental State Examination (MMSE) 4 & 8 weeks 2.4. Functional Assessment Staging of Alzheimer’s Disease (FAST) 4 weeks 2.5. Clinical Frailty Scale (CFS) 4 weeks 2.6. Quality of Life with resident 4 & 8 weeks (QOL-AD care home) 2.7. Quality of Life with proxy informant 4 & 8 weeks (QAULID) 2.8. Pain; Abbey Pain Scale (APS) at 4 weeks 3. Qualitative sub-study outcomes of interest measured using semi-structured interviews at baseline and 8 weeks: 3.1. Attitudes towards cannabis-based medicines 3.2. Issues/benefits of administering via an oromucosal method in this population 3.3. Feasibility and acceptability of wearables in the population 3.4. Factors of regular care home activities/procedures that may facilitate or inhibit effective implementation of Sativex® in practice | — |
Countries
England, United Kingdom
Outcome results
None listed