The Supplementation Therapy in Autism and Response to Treatment Study

Summary

In addition to the "core" symptoms of ASD (i.e., impaired communication, impaired reciprocal social interaction and restricted, repetitive and stereotyped patterns of behaviors or interests), it is estimated that up to 70% of autistic people present at least one comorbid psychiatric disorder, leading to a deterioration in quality of life, a greater demand for support and worse prognosis and outcome. Anxiety and depressive symptoms would seem to be more present in individuals with Level 1 ASD, requiring their prioritisation against core symptoms. To date, the first-line treatment for autistic patients with comorbid depressive and/or anxiety symptoms is still debated and it is not always clear whether they may or may not benefit from psychotherapeutic and conventional psychopharmacological approaches. As such, growing evidence strengthens the therapeutic potential of the endocannabinoid (eCB) system modulation and of eCB-like compounds.

The aim of this study is to provide a response to an unmet clinical need in this framework of psychic vulnerability by initiating oral therapy with palmitoylethanolamide (PEA), a nutraceutical/food supplement with proven anti-inflammatory and neuroprotective properties.

Indeed, many conditions of psychological distress are thought to be underpinned by systemic inflammatory and/or neuroinflammatory processes, on which PEA has shown remarkable efficacy, including through modulation of the immune response and the interaction between the endocannabinoid system and the gut-microbiota-brain axis.

The trial we are proposing is a 12-week open-label phase 2 study involving the daily intake of PEA 600 mg, at a dosage of 1 tablet/day.

This study will be conducted at the Unit of Psychiatry of Santa Maria della Misericordia Udine University Hospital.

Through this study, we wish to evaluate: the ability of PEA to alleviate symptoms of psychic distress (i.e., anxiety and/or depression) in Level 1 autistic adults; the safety and tolerability of sustained intake of PEA in Level 1 autistic adults; and the biological basis of PEA functioning.

The study involves taking PEA orally once daily (600 mg daily) at the same time as a meal during the initial 12-week phase. Upon completion of the initial phase, subjects will be offered to enter an extension phase of the trial of an additional 24 weeks to assess treatment stability, with the possibility of titration of PEA to 1200 mg daily based on observed clinical compensation. Each participant will be on PEA treatment for up to 36 weeks.

During the course of the study, periodic clinical re-evaluations will be conducted at our Day-Hospital setting.

The trial will unfold through one screening visit, one baseline visit, and two follow-up visits (FUP, 4 weeks and 12 weeks apart). The patient will be administered standardized interviews by a qualified investigating physician; clinical objective examination, collection of blood and urine samples for standard hematochemical investigations, collection of blood and stool samples for analysis of some biological markers of interest, monitoring of adherence to therapy intake, side effects, and adverse effects will also be performed during the follow-up visits. The nutraceutical PEA will be dispensed by the clinical investigators at each follow-up visit.

Conditions

• Autism
• Autism Spectrum Disorder
• Autism Spectrum Disorder High-Functioning
• Asperger Syndrome
• Depressive Symptoms
• Anxiety State

Interventions

DIETARY_SUPPLEMENT

Oral Ultramicronized-Palmitoylethanolamide (um-PEA; 600 mg per day) in tablet form

Um-PEA is to be taken orally once a day (600 mg per day) around mealtime during the 12-week initial phase of the study. During the 24-week extension phase of the study, the trial medication is to be taken from once a day up to twice a day (600-1200 mg per day), based on clinical judgment of the improvement obtained so far, around mealtime.

Sponsors & Collaborators

• University of Udine

  lead OTHER

Principal Investigators

• Marco Colizzi, MD, PhD · Unit of Psychiatry, Department of Medicine (DAME), University of Udine (UNIUD)

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

35 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-09-01

Primary Completion

2025-11-30

Completion

2026-11-30

Countries

• Italy

Study Locations