NAbiximols Clinical Translation To the treatment of Pain and Agitation In Severe Dementia (NACTOPAISD): Clinical trial protocol.

Up to 80 % nursing home residents with dementia experiences chronic pain. Contextually, 97 % presents fluctuant neuropsychiatric symptoms (NPS). Among the most challenging is agitation, connected with undertreated pain and managed through neuroleptics doubling death risk. Evidence is accumulating in favor of the involvement of the endocannabinoid system in nociception and NPS. This double-blind, placebo-controlled, randomized trial (NAbiximols Clinical Translation To the treatment of Pain and Agitation In Severe Dementia [NACTOPAISD]) aims at investigating efficacy and safety of oral spray nabiximols, containing Δ9-tetrahydrocannabinol and cannabidiol (Sativex®), for pain and agitation treatment in severe dementia patients (Mini-Mental State Examination ≤ 12) over 65. The coprimary endpoints are efficacy on pain and agitation, assessed through the recently validated Italian Mobilization-Observation-Behavior-Intensity-Dementia and the Cohen-Mansfield Agitation Inventory. The secondary endpoint is the evaluation of efficacy duration after wash-out and the assessment of quality of life through the DEMQOL. Any adverse events will be reported. The results undergo statistical analysis plan. NACTOPAISD might provide rationale for a translational safer pain and agitation treatment in severe dementia. It is approved by Calabria Region Ethics Committee and follows the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) and the Consolidated Standards of Reporting Trials (CONSORT) statements.

Pain and agitation treatment in severe dementia patients: The need for Italian Mobilization-Observation-Behavior-Intensity-Dementia (I-MOBID2) pain scale translation, adaptation and validation with psychometric testing.

The 97% of dementia patients develops fluctuant neuropsychiatric symptoms often related to under-diagnosed and unrelieved pain. Up to 80% severe demented nursing home residents experiences chronic pain due to age-related comorbidities. Patients lacking self-report skills risk not to be appropriately treated for pain. Mobilization-Observation-Behavior-Intensity-Dementia (MOBID2) is the sole pain scale to consider the frequent co-occurrence of musculoskeletal and visceral pain and to unravel concealed pain through active guided movements. Accordingly, the Italian real-world setting can benefit from its translation and validation. This clinical study provides a translated, adapted and validated version of the MOBID2, the Italian I-MOBID2. The translation, adaptation and validation of the scale for non-verbal, severe demented patients was conducted according to current guidelines in a cohort of 11 patients over 65 with mini-mental state examination ≤ 12. The I-MOBID2 proves: good face and scale content validity index (0.89); reliable internal consistency (Cronbach's α = 0.751); good to excellent inter-rater (Intraclass correlation coefficient, and test-retest (ICC = 0.902) reliability. The construct validity is high (Rho = 0.748 p < 0.05 for 11 patients, Spearman rank order correlation of the overall pain intensity score with the maximum item score of I-MOBID2 Part 1; rho=0.895 p < 0.01 for 11 patients, for the overall pain intensity score with the maximum item score of I-MOBID2 Part 2) and a good rate of inter-rater and test-retest agreement was demonstrated by Cohen's K = 0.744. The average execution time is of 5.8 min, thus making I-MOBID2 a useful tool suitable also for future development in community setting with administration by caregivers.

Pharmacological Treatment of Pain and Agitation in Severe Dementia and Responsiveness to Change of the Italian Mobilization-Observation-Behavior-Intensity-Dementia (I-MOBID2) Pain Scale: Study Protocol.

Up to 80% of Alzheimer's disease (AD) patients in nursing homes experiences chronic pain and 97% develops fluctuant neuropsychiatric symptoms (NPS). Agitation, associated with unrelieved pain, is managed through antipsychotics and may increase the risk of death. Evidence is accumulating in favor of analgesia for a safer, effective therapy of agitation. The Italian version of Mobilization-Observation-Behavior-Intensity-Dementia, I-MOBID2, recently validated in the Italian setting, shows: good scale content validity index (0.89), high construct validity (Spearman rank-order correlation Rho = 0.748), reliable internal consistency (Cronbach's α coefficient = 0.751), good-excellent inter-rater (intraclass correlation coefficient, ICC = 0.778) and test-retest (ICC = 0.902) reliability, and good inter-rater and test-retest agreement (Cohen's K = 0.744) with 5.8 min completion time. This study intends to identify the responsiveness of the I-MOBID2 based on COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) recommendations, assessing the a priori hypotheses of (1) the efficacy of painkillers administered to severe AD patients after proper pain assessment and (2) the effect of reduction of the Cohen-Mansfield Agitation Inventory (CMAI) score and of agitation rescue medications. This protocol is approved by Calabria Region Ethics Committee protocol No. 31/2017 and follows the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines.