The Supplementation Therapy in Autism and Response to Treatment Study

NCT06187090 | Recruiting

• 1 other identifier: IRB-DAME 188/2023
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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

Outcome Measures

Primary Outcomes (1)

• Symptom-Checklist-90-R

  Global improvement in symptom intensity and psychological distress associated with autism through the Global Score Index (GSI) of the SCL-90-R

  12 weeks for the initial phase, further 24 weeks for the extension phase

Secondary Outcomes (4)

• World Health Organization Disability Assessment Schedule 2.0

  12 weeks for the initial phase, further 24 weeks for the extension phase

• Hospital Anxiety and Depression Scale

  12 weeks for the initial phase, further 24 weeks for the extension phase

• Symptom-Checklist-90-R

  12 weeks for the initial phase, further 24 weeks for the extension phase

• World Health Organization Disability Assessment Schedule 2.0

  12 weeks for the initial phase, further 24 weeks for the extension phase

Study Arms (1)

PEA Arm

EXPERIMENTAL

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

Interventions

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

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.

PEA Arm

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Individuals diagnosed with Level 1 ASD, as defined using Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5);
• Aged 18-35 years;
• To be able to understand and communicate in Italian;
• To be able to give informed consent.

You may not qualify if:

• Level 2 or Level 3 ASD, as defined using Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) \[47\];
• Current diagnosis of a co-occurring major psychiatric disorder (e.g., major depressive disorder, bipolar affective disorder, psychotic disorders);
• Active suicidal ideation indicating significant current risk or history of serious suicide attempt in the opinion of the PI, as evaluated at the screening stage;
• Lifetime neurological disorders (e.g., epilepsy, except febrile convulsions) or severe intercurrent physical illness;
• Current treatment with psychotropic medication, with the exception of Selective Serotonin Reuptake Inhibitor (SSRI) stable monotherapy (at least 8 months);
• IQ \< 70;
• Female patients who are pregnant, lactating or not using an acceptable effective form contraception if they are at risk of falling pregnant;
• Taking part in another pharmacological trial.

Sponsors & Collaborators

• University of Udine: lead

Study Sites (1)

Unit of Psychiatry, University Hospital of Udine

Udine, UD, 33100, Italy

RECRUITING

Related Publications (5)

• Bortoletto R, Piscitelli F, Candolo A, Bhattacharyya S, Balestrieri M, Colizzi M. Questioning the role of palmitoylethanolamide in psychosis: a systematic review of clinical and preclinical evidence. Front Psychiatry. 2023 Jul 18;14:1231710. doi: 10.3389/fpsyt.2023.1231710. eCollection 2023.

  PMID: 37533892 RESULT

• Colizzi M, Bortoletto R, Costa R, Zoccante L. Palmitoylethanolamide and Its Biobehavioral Correlates in Autism Spectrum Disorder: A Systematic Review of Human and Animal Evidence. Nutrients. 2021 Apr 18;13(4):1346. doi: 10.3390/nu13041346.

  PMID: 33919499 RESULT

• Colizzi M, Bortoletto R, Colli C, Bonomo E, Pagliaro D, Maso E, Di Gennaro G, Balestrieri M. Therapeutic effect of palmitoylethanolamide in cognitive decline: A systematic review and preliminary meta-analysis of preclinical and clinical evidence. Front Psychiatry. 2022 Oct 28;13:1038122. doi: 10.3389/fpsyt.2022.1038122. eCollection 2022.

  PMID: 36387000 RESULT

• Bortoletto R, Balestrieri M, Bhattacharyya S, Colizzi M. Is It Time to Test the Antiseizure Potential of Palmitoylethanolamide in Human Studies? A Systematic Review of Preclinical Evidence. Brain Sci. 2022 Jan 12;12(1):101. doi: 10.3390/brainsci12010101.

  PMID: 35053844 RESULT

• Khalaj M, Saghazadeh A, Shirazi E, Shalbafan MR, Alavi K, Shooshtari MH, Laksari FY, Hosseini M, Mohammadi MR, Akhondzadeh S. Palmitoylethanolamide as adjunctive therapy for autism: Efficacy and safety results from a randomized controlled trial. J Psychiatr Res. 2018 Aug;103:104-111. doi: 10.1016/j.jpsychires.2018.04.022. Epub 2018 May 1.

  PMID: 29807317 RESULT

MeSH Terms

Conditions

Autistic Disorder; Autism Spectrum Disorder; Asperger Syndrome; Depression; Anxiety Disorders

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Study Officials

• Marco Colizzi, MD, PhD

  Unit of Psychiatry, Department of Medicine (DAME), University of Udine (UNIUD)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marco Colizzi, MD, PhD

CONTACT

+390432559155; marco.colizzi@uniud.it

Riccardo Bortoletto, MD

CONTACT

+393484739255; bortoletto.riccardo@spes.uniud.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 12-week, open-label, investigator-initiated proof-of-concept study

Study Record Dates

• First Submitted: December 15, 2023
• First Posted: January 2, 2024
• Study Start: September 1, 2023
• Primary Completion: November 1, 2025
• Study Completion (Estimated): November 1, 2026
• Last Updated: January 2, 2024

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)