Clinically significant agitation in Alzheimer's Diseases MedDRA version: 21.1 Level: LLT Classification code 10001499 Term: Agitation mental System Organ Class: 10037175 - Psychiatric disorders MedDRA version: 20.0 Level: PT Classification code 10001497 Term: Agitation System Organ Class: 10037175 - Psychiatric disorders
Conditions
Interventions
Trade Name: Sativex Oromucosal Spray
Product Name: Sativex Oromucosal Spray
Pharmaceutical Form: Oromucosal spray
INN or Proposed INN: DELTA-9-TETRAHYDROCANNABINOL
CAS Number: 1972-08-3
Other descri
Sponsors
Kings's College London
South London and Maudsley NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Age: 55-90. 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). Clinically significant A/A that requires treatment, defined by CMAI >/= 45 (Cohen-Mansfield et al., 1989) and/or NPI-NH Agitation total score >/= 4 (Livingston et al., 2017). Residential within a nursing home at recruitment to the study with a history of at least 2 weeks behavioural disturbance. 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 6 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 54
Exclusion criteria
Exclusion criteria: - 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). - ChEIs (donepezil, rivastigmine or galantamine) and/or memantine, dosage alteration in the 6 weeks prior to the start of the study. - Currently using cannabis-based medicine(s) (defined as being a UK licensed product prescribed by a doctor) - Concomitant treatment with strong enzyme inducers (rifampicin, carbamazepine, phenytoin, phenobarbital, St John’s Wort) and/or CYP3A4 inhibitors - Hypersensitivity to Sativex® or any of the excipients in the formulation (ethanol anhydrous, Propylene glycol, peppermint oil). - Severe cardiovascular disease, recent myocardial infarction (‘recency’ determined by study doctor according to clinical significance), uncompensated congestive heart failure and uncontrolled hypertension. o QT interval by Fredericia (QTcF) greater than 450 will be excluded if ECG conducted - Severe, unstable or poorly controlled medical illness. - Renal Impairment as defined by estimated Glomerular Filtration Rate (eGFR) less than 45ml/min - Hepatic impairment as 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) - Any disability that may interfere with the patient completing the study procedure. - 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. - Delirium, pain or any medical illness as a clear cause of agitation - 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)’. - Evidence of ‘suicidality risk’ determined by >0 on Columbia-Suicide Severity Rating Scale (C-SSRS) - History/current seizure disorder - History/current of alcohol or other substance abuse - History of fall(s) within the last 6 months 7.2.1 COVID-19 specific exclusion criteria - Positive COVID test result within previous 4 weeks - Currently experiencing CV19 symptoms (continuous cough, high temperature, loss of taste/smell). NB. can be re-screened after 2 weeks
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Feasibility: To employ a mixed methods approach to explore the feasibility of a definitive multicentre randomized controlled trial (RCT) within residential nursing home settings of Sativex® for treatment of agitation and aggression in AD. Further, our primary objectives will be; 1. To explore rate of recruitment and retention in the target population, including determining facilitators and barriers. 2. To determine whether the cut-off of ‘clinically significant’ agitation for CMAI or NPI-NH influences rate of recruitment fora future confirmatory trial 3. To investigate the acceptability of an oral mucosal method of administration for this indication in terms of compliance and to care home staff in terms of adherence to the titration schedule. 4. To investigate the acceptability of a cannabinoid-based medicine, and explore impact of societal attitudes and stigma within this patient population as part of the qualitative evaluation.;Secondary Objective: - To estimate the parameters in a sample size for a later RCT for the treatment effect of Sativex® for agitation and aggression in dementia. - To explore the overall response rate of Sativex® in the trial population, including other neuropsychiatric symptoms, such as sleep disturbances and changes in appetite, and pain relief. - Explore Actigraphy data for sleep, physical activity and linked to NPS assessments (exploratory analyses) weeks 2-4 ;Primary end point(s): Feasibility outcomes: To consent and randomise 60 participants within a 12-month data collection period (equalling a recruitment rate of 5 participants a month). To follow up at least 75% of those randomised at 4 weeks. For a minimum of 80% of participants to demonstrate adherence to the allocation. To estimate a clinically meaningful effect size of at least 0.3 ;Timepoint(s) of evaluation of this end point: Feasibility endpoints will be evaluated at the end of the trial. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Safety & tolerability: - ongoing evaluation throughout trial, and end of trial Neuropsychiatric Symptoms, cognition, pain, quality of life: - Change in CMAI at 2 & 8 weeks - NPI-NH - 2, 4 & 8 weeks - MMSE - 4 & 8 weeks - FAST - 4 weeks - CFS - 4 weeks - QOL-AD with resident 4 & 8 weeks - QOLID with proxy informant 4 & 8 weeks - Change in pain; APS - 4 weeks - Adverse Events (from baseline to 8 weeks) - Serious Adverse Events (from baseline to 8 weeks) - Physical activity, sedentary behaviour and sleep disturbances from raw accelerometer data (weeks 2-4) - Co-prescribed psychotropic medications, - from baseline to 8 weeks - Number of recorded incidents of aggression, and number of occasions rescue treatment utilised - from baseline to 8 weeks ;Secondary end point(s): Safety and tolerability: Tolerability: Assessed by self- & carer-report of side-effects & medication discontinuation. Safety parameters: Bloods for Haematology (Full blood count and Haemoglobin) and Biochemistry (Urea & Electrolytes, liver function test, thyroid function test, lipid profile); Vital signs: Heart rate and Blood pressure; Physical examination. Follow up phone calls for self-reported side effects, including incidence of falls and compliance (week 2 and 6). Neuropsychiatric Symptoms, cognition, pain, quality of life: Tertiary Endpoints - Change in CMAI at 2 & 8 weeks - Neuropsychiatric Inventory – Nursing Home (NPI-NH) 2, 4 & 8 weeks - Mini Mental State Examination (MMSE) 4 & 8 weeks - Functional Assessment Staging of Alzheimer’s Disease (FAST) 4 weeks - Clinical Frailty Scale (CFS) 4 weeks - Quality of Life with resident 4 & 8 weeks (QOL-AD care home) - Quality of Life with proxy informant 4 & 8 weeks (QAULID) - Change in pain; Abbey Pain Scale (APS) 4 weeks - Adverse Events (from baseline to 8 weeks) - Serious Adverse Events (from baseline to 8 weeks) - Physical activity, sedentary behaviour and sleep disturbances from raw accelerometer da | — |
Countries
United Kingdom
Contacts
Public ContactChris Albertyn
Kings College London
Outcome results
None listed