Endocannabinoid Activity Remodulation for Psychosis Liability in Youth (EARLY)
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ClinicalTrials.gov Identifier: NCT06037993 |
Recruitment Status :
Recruiting
First Posted : September 14, 2023
Last Update Posted : September 21, 2023
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Clinical High-Risk (CHR) for Psychosis is characterized by the occurrence of unusual stressful experiences (attenuated psychotic symptoms, APS), anxious symptoms, psychological distress, and substantial impairment of the subject's daily functioning.
It is estimated to be associated with up to 30-35% risk of evolution to frank psychotic disorder within 2-2.5 years. To date, no psychotherapeutic or pharmacological approaches have shown therapeutic evidence in this group of patients.
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 APS, anxiety, and psychic distress in CHR-APS individuals; the safety and tolerability of sustained intake of PEA in CHR-APS individuals; 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.
Condition or disease | Intervention/treatment | Phase |
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Clinical High Risk for Psychosis Ultra High Risk for Psychosis Attenuated Psychotic Symptoms | Dietary Supplement: Ultra-micronized Palmitoylethanolamide (PEA) | Not Applicable |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 20 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Intervention Model Description: | We will evaluate the study viability through an internal pilot that will assess the ability of the study to identify, consent, and follow up CHR patients experiencing APS in the study. We propose a 12-week, open-label, investigator-initiated proof of concept study (Phase-2 Pilot Study) of PEA (600 mg/day) for the treatment of APS in CHR patients. We plan to enrol 20 CHR young adults. Those completing the 12-week initial phase, will be proposed to enter a 24-week extension phase to evaluate the clinical stability of treatment, with the possibility of PEA titration to 1200 mg/day based on clinical improvement obtained so far. |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Endocannabinoid Activity Remodulation for Psychosis Liability in Youth (EARLY) |
Actual Study Start Date : | November 1, 2022 |
Estimated Primary Completion Date : | November 2024 |
Estimated Study Completion Date : | November 2025 |
Arm | Intervention/treatment |
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Experimental: PEA arm
Palmitoylethanolamide (PEA)-treated patients
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Dietary Supplement: Ultra-micronized Palmitoylethanolamide (PEA)
Palmitoylethanolamide (PEA) is an N-acylethanolamine (AE), produced "on demand" by different cell types as a response to actual or potential damage, proven to down-regulate central and peripheral activity of mast cells and non-neuronal cells (e.g., astrocytes, microglia) and to exert protective functions against glutamate neuro-toxicity, accounting for its naturally-occurring anti-inflammatory, analgesic, and anticonvulsant properties. Due to the shared pharmacodynamic properties, PEA is considered as the endogenous equivalent of Cannabidiol (CBD). A growing body of literature has confirmed the role of PEA in most neurobiological mechanisms underpinning several neuropsychiatric conditions both in clinical and preclinical settings. The effect of PEA over neuroinflammation and glutamate signaling may represent a promising biobehavioral mechanism underlying the clinical utility of its oral supplementation in CHR state. |
- Severity of attenuated psychotic symptoms (APS) [ Time Frame: 12 weeks for the initial phase, further 24 weeks for the extension phase ]Comprehensive Assessment of At-Risk Mental State (CAARMS)
- Distress associated with psychotic symptoms [ Time Frame: 12 weeks for the initial phase, further 24 weeks for the extension phase ]Comprehensive Assessment of At-Risk Mental State (CAARMS)
- Severity of anxiety symptoms [ Time Frame: 12 weeks for the initial phase, further 24 weeks for the extension phase ]Hospital Anxiety and Depression Scale (HADS)
- Level of impaired global functioning [ Time Frame: 12 weeks for the initial phase, further 24 weeks for the extension phase ]Social and Role functioning Scale
- Clinical remission, defined as no longer meeting the APS criteria [ Time Frame: 12 weeks for the initial phase, further 24 weeks for the extension phase ]Comprehensive Assessment of At-Risk Mental State (CAARMS)
- Total CAARMS score [ Time Frame: 12 weeks for the initial phase, further 24 weeks for the extension phase ]Comprehensive Assessment of At-Risk Mental State (CAARMS)
- Safety endpoints: Incidence of adverse effects during the study period [ Time Frame: 12 weeks for initial phase, further 24 weeks for the extension phase ]UKU side-effect rating scale
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Ages Eligible for Study: | 18 Years to 35 Years (Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria
- Individuals diagnosed with CHR-APS, as defined using CAARMS criteria;
- Aged 18-35 years;
- To be able to understand and communicate in Italian;
- To be able to give informed consent.
Exclusion Criteria
- Lifetime history of a psychotic or manic episode lasting 7 days or longer;
- 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);
- Lifetime treatment with antipsychotic medication for more than 7 days;
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06037993
Contact: Marco Colizzi, MD, PhD | +390432559155 | marco.colizzi@uniud.it | |
Contact: Riccardo Bortoletto, MD | +393484739255 | bortoletto.riccardo@spes.uniud.it |
Italy | |
Unit of Psychiatry, University Hospital of Udine | Recruiting |
Udine, UD, Italy, 33100 | |
Contact: Marco Colizzi, MD, PhD +390432559155 marco.colizzi@uniud.it | |
Contact: Riccardo Bortoletto, MD +393484739255 bortoletto.riccardo@spes.uniud.it | |
Principal Investigator: Marco Colizzi, MD, PhD | |
Sub-Investigator: Riccardo Bortoletto, MD | |
Unit of Psychiatry, University Hospital of Udine | Recruiting |
Udine, Italy, 33100 | |
Contact: Marco Colizzi, MD, PhD +390432559155 marco.colizzi@uniud.it |
Principal Investigator: | Marco Colizzi, MD, PhD | University of Udine |
Responsible Party: | University of Udine |
ClinicalTrials.gov Identifier: | NCT06037993 |
Other Study ID Numbers: |
IRB-DAME 93/2023 |
First Posted: | September 14, 2023 Key Record Dates |
Last Update Posted: | September 21, 2023 |
Last Verified: | September 2023 |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
Product Manufactured in and Exported from the U.S.: | No |
At-Risk Mental State Schizophrenia Endocannabinoid System Gut-Brain Axis |
Palmitoylethanolamide Nutraceuticals Prevention Early Intervention |
Psychotic Disorders Mental Disorders Schizophrenia Spectrum and Other Psychotic Disorders Palmidrol Analgesics Sensory System Agents Peripheral Nervous System Agents Physiological Effects of Drugs Anti-Inflammatory Agents, Non-Steroidal Analgesics, Non-Narcotic |
Anti-Inflammatory Agents Antirheumatic Agents Antiviral Agents Anti-Infective Agents Cannabinoid Receptor Agonists Cannabinoid Receptor Modulators Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Hormones Hormones, Hormone Substitutes, and Hormone Antagonists |