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

Stroke Clinical Trial

— BEO  

Official title:

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.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04321889
• Other study ID #: ISA-BEO092019
• Status: Not yet recruiting
• Phase: N/A
• Start date: April 1, 2020
• Est. completion date: June 30, 2021

Study information

• Verified date: March 2020
• Source: S.Anna Rehabilitation Institute
• Contact: Loris Pignolo, Researcher
• Phone: 3996223973
• Email: l.pignolo[@]isakr.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 134
• Est. completion date: June 30, 2021
• Est. primary completion date: December 10, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Dementia
• Severe Dementia
• Stroke

Intervention

Device:
• defurocumarinized bergamot loaded in a nanotechnological essential oil release system
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.

Other:
• Placebo
nanotechnological system loaded with placebo cream

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
S.Anna Rehabilitation Institute

References & Publications (6)

Berliocchi L, Russo R, Maiarù M, Levato A, Bagetta G, Corasaniti MT. Autophagy impairment in a mouse model of neuropathic pain. Mol Pain. 2011 Oct 24;7:83. doi: 10.1186/1744-8069-7-83. — View Citation

Sakurada T, Kuwahata H, Katsuyama S, Komatsu T, Morrone LA, Corasaniti MT, Bagetta G, Sakurada S. Intraplantar injection of bergamot essential oil into the mouse hindpaw: effects on capsaicin-induced nociceptive behaviors. Int Rev Neurobiol. 2009;85:237-48. doi: 10.1016/S0074-7742(09)85018-6. Review. — View Citation

Sakurada T, Mizoguchi H, Kuwahata H, Katsuyama S, Komatsu T, Morrone LA, Corasaniti MT, Bagetta G, Sakurada S. Intraplantar injection of bergamot essential oil induces peripheral antinociception mediated by opioid mechanism. Pharmacol Biochem Behav. 2011 Jan;97(3):436-43. doi: 10.1016/j.pbb.2010.09.020. Epub 2010 Oct 13. — View Citation

Scuteri D, Crudo M, Rombolà L, Watanabe C, Mizoguchi H, Sakurada S, Sakurada T, Greco R, Corasaniti MT, Morrone LA, Bagetta G. Antinociceptive effect of inhalation of the essential oil of bergamot in mice. Fitoterapia. 2018 Sep;129:20-24. doi: 10.1016/j.fitote.2018.06.007. Epub 2018 Jun 12. — View Citation

Scuteri D, Morrone LA, Rombolà L, Avato PR, Bilia AR, Corasaniti MT, Sakurada S, Sakurada T, Bagetta G. Aromatherapy and Aromatic Plants for the Treatment of Behavioural and Psychological Symptoms of Dementia in Patients with Alzheimer's Disease: Clinical Evidence and Possible Mechanisms. Evid Based Complement Alternat Med. 2017;2017:9416305. doi: 10.1155/2017/9416305. Epub 2017 Mar 30. Review. — View Citation

Scuteri D, Rombolà L, Morrone LA, Bagetta G, Sakurada S, Sakurada T, Tonin P, Corasaniti MT. Neuropharmacology of the Neuropsychiatric Symptoms of Dementia and Role of Pain: Essential Oil of Bergamot as a Novel Therapeutic Approach. Int J Mol Sci. 2019 Jul 6;20(13). pii: E3327. doi: 10.3390/ijms20133327. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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