Efficacy of Defurocumarinized Bergamot in the Treatment of Agitation in Severe Dementia Patients.

Study Overview
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Brief Summary
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This study evaluates the efficacy of defurocumarinized bergamot in the treatment of agitation in severe dementia patients. Bergamot essential oil (BEO), able to modulate the endogenous, peripheral and central opioid system involved in painful states, has developed in models of inflammatory pain and neuropathic pain; it is also effective when administered by inhalation. Participants in the study will be divided into 2 parallel groups, one treatment group and one placebo, to evaluate the clinical efficacy of defurocumarinized bergamot loaded in a nanotechnological system of essential oil release in the pharmaceutical form of a cream in the treatment of agitation, in in Over-sixty-five-year-old patients of both sexes diagnosed with severe dementia.

Detailed Description
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According to the World Alzheimer's Report 2018, 50 million people worldwide suffer from dementia and it is estimated that this number will triple by 2050. Very often people with dementia suffer from comorbidities accompanied by chronic, inflammatory and neuropathic pain, often under-diagnosed through psychological and behavioral symptoms of dementia such as agitation and aggression. The therapy of neuropsychiatric symptoms of dementia is currently based on the use of atypical antipsychotics that are actually present in the short term and may induce important side effects. This study evaluates the efficacy of defurocumarinized bergamot in the treatment of agitation in severe dementia patients. Bergamot essential oil (BEO), able to modulate the endogenous, peripheral and central opioid system involved in painful states, has developed in models of inflammatory pain and neuropathic pain; it is also effective when administered by inhalation. To solve this problem, this clinical trial will use defurocumarinized bergamot loaded in a nanotechnological system of essential oil release in the pharmaceutical form of an odourless cream indistinguishable from placebo cream. Participants in the study will be divided into 2 parallel groups, one treatment group and one placebo, to evaluate the clinical efficacy of defurocumarinized bergamot loaded in a nanotechnological system of essential oil release in the pharmaceutical form of a cream in the treatment of agitation, in in Over-sixty-five-year-old patients of both sexes diagnosed with severe dementia. The rationale of this clinical trial is based on three fundamental points: Preclinical research has proven, beyond any doubt, a powerful analgesic activity of BEO on inflammatory and neuropathic pain; at present the essential oils needed in aromatherapy for agitation management do not show strong analgesic activity, documented by extensive preclinical evidence; clinical trials that have assessed the efficacy of aromatherapy in neuropsychiatric symptoms associated with dementia suffer from the severe lack of a double-blind according to the most rigorous criteria of clinical trial evaluation. To solve this problem, this clinical trial will use defurocumarinized bergamot loaded in a nanotechnological system of essential oil release in the pharmaceutical form of an odourless cream indistinguishable from placebo cream.

Official Title
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Randomized Double-blind Controlled Trial to Evaluate the Efficacy of Defurocumarinized Bergamot Loaded in a Nanotechnological System for the Release of Essential Oil in the Treatment of Agitation in Severe Dementia Patients.

Conditions
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Severe Dementia, Stroke

Intervention / Treatment
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* Device: defurocumarinized bergamot loaded in a nanotechnological essential oil release system
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of severe dementia by MMSE score<12; Signature of informed consent by a family member/caregiver/support administrator; The use of authorised and concomitant therapies for the treatment of agitation is permitted. Exclusion Criteria: -Positive remote case history for pre-existing neurological or psychiatric disabling conditions

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized double-blind placebo clinical trial for parallel groups to evaluate the clinical efficacy of defurocumarinized bergamot loaded in a nanotechnological system of essential oil release in the pharmaceutical form of a cream in the treatment of agitation, in patients of both sexes with severe dementia diagnosis. Subjects will be eligible if they meet all inclusion criteria. A total of 134 patients will be enrolled, randomized, in a 1:1 ratio, to treatment with defurocumarinized bergamot loaded in a nanotechnological release system or placebo.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BEO<br>Subjects of both sexes of age >65 years who have received diagnosis of severe dementia and clinically relevant agitation hospitalized in the enrolment center. | Device: defurocumarinized bergamot loaded in a nanotechnological essential oil release system<br>* Patients will be treated either with placebo cream or with defurocumarinized bergamot loaded in a nanotechnological system of essential oil release in the pharmaceutical form of cream 2 times a day for 4 weeks. The subject will be monitored throughout the treatment and for at least 4 weeks after the end of the treatment.<br>|
| Placebo Comparator: Placebo<br>Subjects of both sexes of age >65 years who have received diagnosis of severe dementia and clinically relevant agitation hospitalized in the enrolment center. | Other: Placebo<br>* nanotechnological system loaded with placebo cream<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment of agitation | To evaluate the clinical efficacy of defurocumarinized bergamot l in the treatment of agitation in patients with severe dementia by determination of the Cohen-Mansfield Agitation Inventory (CMAI)score. CMAI is a 29-item scale widely used to assess agitation. | up to 6 weeks after the end of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of the effect on agitation | Carry out a follow-up following suspension of the treatment with defurocumarinized bergamot loaded in a nanotechnology essential oil release system to assess the duration of the effect on agitation, using Cohen-Mansfield Agitation Inventory (CMAI) score. CMAI is a 29-item scale widely used to assess agitation. | 6 weeks after the end of treatment | 
| clinical efficacy on pain | Determine the clinical efficacy of defurocumarinized bergamot, loaded in a nanotechnological system of essential oil release in the pharmaceutical form of a cream, on pain in patients with severe dementia by determining the weekly score of the Mobilization-Observation-Behaviour-Intensity-Dementia (MOBID)-2 pain assessment scale. MOBID-2 is an extended version of the MOBID pain scale and consists of two parts: Part 1 is the previous MOBID and is used for the assessment of musculoskeletal pain through the observation of painful behaviour when performing five guided movements of different parts of the body in order to assign a score to the pain intensity; Part 2 is used for the assessment of pain from internal organs, head and skin, through behavioural indicators of pain and pain localization on the pain site illustrations. | 6 weeks after the end of treatment |