Palmitoylethanolamide Combined With Luteoline in Frontotemporal Dementia Patients. A Randomized Controlled Trial (PEA-FTD)

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.

Study Overview

• Status: Completed
• Conditions: Frontotemporal Dementia
• Intervention / Treatment: Dietary supplement: PEA-LUT; Dietary supplement: PLACEBO

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Rome, Italy, 00179
    • Giacomo Koch
  • Rome, Italy, 00179
    • Santa Lucia Foundation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PEA-LUT; PEA-LUT administration at the oral dosage of 700 mg x 2/day for 24 weeks	Dietary supplement: PEA-LUT; PEA-LUT administration at the oral dosage of 700 mg x 2/day
Placebo Comparator: PLACEBO; PLACEBO administration at the oral dosage of 700 mg x 2/day for 24 weeks	Dietary supplement: PLACEBO; PLACEBO administration at the oral dosage of 700 mg x 2/day

What is the study measuring?

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
Neuropsychiatric Inventory (NPI)	Battery to assess behavioral changes	24 weeks
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
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

Collaborators and Investigators

• Sponsor: I.R.C.C.S. Fondazione Santa Lucia

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2019
• Primary Completion (Actual): December 30, 2022
• Study Completion (Actual): June 30, 2023

Study Registration Dates

• First Submitted: April 13, 2020
• First Submitted That Met QC Criteria: July 24, 2020
• First Posted (Actual): July 28, 2020

Study Record Updates

• Last Update Posted (Actual): November 2, 2023
• Last Update Submitted That Met QC Criteria: October 31, 2023
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: dopamine; GABA; frontal cortex
• Additional Relevant MeSH Terms: Mental Disorders; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Neurocognitive Disorders; Neurodegenerative Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Language Disorders; Communication Disorders; Speech Disorders; Frontotemporal Lobar Degeneration; Aphasia; Dementia; Frontotemporal Dementia; Aphasia, Primary Progressive; Pick Disease of the Brain
• Other Study ID Numbers: SPE.107

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No