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

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.

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.

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:

1. Preclinical research has proven, beyond any doubt, a powerful analgesic activity of BEO on inflammatory and neuropathic pain;
2. at present the essential oils needed in aromatherapy for agitation management do not show strong analgesic activity, documented by extensive preclinical evidence;
3. 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.

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