Palmitoylethanolamide Combined With Luteoline in Frontotemporal Dementia Patients. A Randomized Controlled Trial

Study Overview
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Brief Summary
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Frontotemporal dementia (FTD) is a devastating neurodegenerative disorder. It is the second most frequent cause of presenile neurodegenerative dementia in those less than 65 years of age. Currently, there is no effective pharmacological treatment to slow down the progression of FTD. Recently, it has been proposed that neuroinflammation could be involved in specific forms of FTD and that novel drugs targeting neuroinflammation could potentially be useful in FTD treatment. An available form of ultra-micronized PEA combined with luteoline (PEA-LUT) has gained attention for its proven anti-inflammatory and neuroprotective properties reported in neurodegenerative conditions related to FTD, such as Amyotrophic Lateral Sclerosis. The administration of PEA-LUT treatment may have a clinical impact in behavioural variant FTD (bv-FTD) patients. In particular, PEA-LUT treatment could be able to reduce behavioural disturbances, the more disabling symptoms in bv-FTD, with a related improvement of daily living activities of affected people. Moreover, a multimodal approach (cognitive/neurophysiological) can be used to assess the brain correlates related to the clinical improvement associated with PEA-LUT treatment, thus making remarkable strides in understanding how FTD affects the brain. Potentially the proposed project could provide a valid treatment for cognitive and behavioural dysfunction in FTD patients, with consistent impact for the National Health Systems and minimum cost for the patients.

Official Title
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Palmitoylethanolamide Combined With Luteoline in Frontotemporal Dementia Patients. A Randomized Controlled Trial

Conditions
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Frontotemporal Dementia

Intervention / Treatment
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* Dietary Supplement: PEA-LUT
* Dietary Supplement: PLACEBO


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient has a diagnosis of probable Frontotemporal dementia behavioural variant (bv-FTD) based on the International consensus clinical diagnostic criteria described by Rascovsky et al., 2011. The patient is a man or a woman, aged from 40 to 85 years. The patient has a Clinical Dementia Rating-FTD (CDR-FTD) total score of ≤2 at Screening. The patient has not been treated with acetylcholinesterase inhibitor (AChEI), i.e., donepezil, galantamine, or rivastigmine, at the time of screening. The patient is able to comply with the study procedures in the view of the investigator. Evidence of frontotemporal hypometabolism at PET imaging. Evidence of amyloid markers excluding Alzheimer's disease (cerebrospinal fluid Abeta/Tau dosages or amyloid PET imaging). Exclusion Criteria: Significant neurodegenerative disorder of the central nervous system other than FTD e.g., Alzheimer's disease, Lewy body dementia, Parkinson's disease, multiple sclerosis, progressive supranuclear palsy, normal pressure hydrocephalus, Huntington's disease, any condition directly or indirectly caused by Transmissible Spongiform Encephalopathy (TSE), Creutzfeldt-Jakob Disease (CJD), variant Creutzfeldt-Jakob Disease (vCJD), or new variant Creutzfeldt-Jakob Disease (nvCJD) Significant intracranial focal or vascular pathology seen on brain MRI scan within a maximum of 6 months before Baseline leading to a diagnosis other than probable FTD. The patients has history of seizure (with the exception of febrile seizures in childhood). Metal implants in the head (except dental), pacemaker, cochlear implants, or any other non-removable items that are contraindications to MR imaging. Treatment currently or within 3 months before Baseline with any of the following medications: Typical and Atypical antipsychotics (i.e., Clozapine, Olanzapine); Antiepileptics drugs (i.e., Carbamazepine, Primidone, Pregabalin, Gabapentin); Antidepressants (i.e., Citalopram, Duolxetine, Paroxetine).

Ages Eligible for Study
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Minimum Age: 40 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PEA-LUT<br>PEA-LUT administration at the oral dosage of 700 mg x 2/day for 24 weeks | Dietary Supplement: PEA-LUT<br>* PEA-LUT administration at the oral dosage of 700 mg x 2/day<br>|
| Placebo Comparator: PLACEBO<br>PLACEBO administration at the oral dosage of 700 mg x 2/day for 24 weeks | Dietary Supplement: PLACEBO<br>* PLACEBO administration at the oral dosage of 700 mg x 2/day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Dementia Rating Scale- Frontotemporal dementia Sumo of Boxes (CDR-FTD-SOB) | Battery to evaluate global disease severity | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frontal Assessment Battery (FAB) | Battery to evaluate executive functions | 24 weeks | 
| Screening for aphasia in Neurodegeneration (SAND) | battery to evaluate language functions | 24 weeks | 
| Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) | battery to evaluate activities of daily living | 24 weeks | 
| Mini Mental State Examination (MMSE) | battery to evaluate global cognition | 24 weeks | 
| Long intracortical inhibition (LICI) | TMS protocol to evaluate GABA(B)ergic transmission | 24 weeks | 
| Sort intracortical inhibition (SICI) | TMS protocol to evaluate GABA(B)ergic transmission | 24 weeks | 
| TMS-EEG | power in beta-gamma band to evaluate prefrontal cortical oscillatory activity | 24 weeks | 
| Neuropsychiatric Inventory (NPI) | Battery to assess behavioral changes | 24 weeks | 
| Addenbrooke's Cognitive Examination Revised (ACE-R) | Battery to evaluate global cognition changes | 24 weeks | 
| Frontal Behavioural Inventory | Battery to evaluate behavioural functions | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dopamine, frontal cortex, GABA