Clinical trial NCT04489017: Palmitoylethanolamide Combined With Luteoline in Frontotemporal Dementia Patients. A Randomized Controlled Trial
Official title: Palmitoylethanolamide Combined With Luteoline in Frontotemporal Dementia Patients. A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Frontotemporal Dementia
Keywords: dopamine
frontal cortex
GABA
Lead sponsor: I.R.C.C.S. Fondazione Santa Lucia
Sponsor class: OTHER
First posted: 2020-07-28
Enrollment: 50
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. 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.
2. The patient is a man or a woman, aged from 40 to 85 years.
3. The patient has a Clinical Dementia Rating-FTD (CDR-FTD) total score of ≤2 at Screening.
4. The patient has not been treated with acetylcholinesterase inhibitor (AChEI), i.e., donepezil, galantamine, or rivastigmine, at the time of screening.
5. The patient is able to comply with the study procedures in the view of the investigator.
6. Evidence of frontotemporal hypometabolism at PET imaging.
7. Evidence of amyloid markers excluding Alzheimer's disease (cerebrospinal fluid Abeta/Tau dosages or amyloid PET imaging).

Exclusion Criteria:

1. 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)
2. 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.
3. The patients has history of seizure (with the exception of febrile seizures in childhood).
4. Metal implants in the head (except dental), pacemaker, cochlear implants, or any other non-removable items that are contraindications to MR imaging.
5. 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).

Primary outcomes:
measure: Clinical Dementia Rating Scale- Frontotemporal dementia Sumo of Boxes (CDR-FTD-SOB)
timeFrame: 24 weeks
Secondary outcomes:
measure: Frontal Assessment Battery (FAB)
timeFrame: 24 weeks
measure: Screening for aphasia in Neurodegeneration (SAND)
timeFrame: 24 weeks
measure: Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)
timeFrame: 24 weeks
measure: Mini Mental State Examination (MMSE)
timeFrame: 24 weeks
measure: Long intracortical inhibition (LICI)
timeFrame: 24 weeks
measure: Sort intracortical inhibition (SICI)
timeFrame: 24 weeks
measure: TMS-EEG
timeFrame: 24 weeks
measure: Neuropsychiatric Inventory (NPI)
timeFrame: 24 weeks
measure: Addenbrooke's Cognitive Examination Revised (ACE-R)
timeFrame: 24 weeks
measure: Frontal Behavioural Inventory
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Rome
country: Italy
facility: Giacomo Koch
city: Rome
country: Italy
facility: Santa Lucia Foundation
Study officials:
References: