Endocannabinoid Activity Remodulation for Psychosis Liability in Youth (EARLY)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Severity of attenuated psychotic symptoms (APS)
研究概览
简要总结
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.
详细描述
- STATE OF THE ART Among clinical high-risk (CHR) for psychosis individuals, 30-35 % will develop a full-blown disorder after 2-2.5 years. To date there are no proper tools to predict whoever will evolve to full-blown psychosis nor first-choice interventions to prevent the risk of progression at 6-12 months. The endocannabinoid (eCB) system stands as a mediator of the dopaminergic and glutamatergic systems via the cannabinoid receptor 1 (CB1) in the central nervous system (CNS) and seems to be early altered in psychosis. Cannabidiol (CBD) has shown promising results as a treatment for both psychosis and CHR, especially by regulating eCBs levels via the peroxisome proliferator activated receptors (PPARs). Recent research has focused on the role of eCB-like compounds interacting with non-CB receptors, to identify novel putative pharmacological targets. To this extent, oral palmitoylethanolamide (PEA) supplementation has shown promising therapeutic effects as an adjunctive treatment for patients with schizophrenia negative symptoms and acute mania. Interestingly, PEA peripheral blood levels are elevated in CHR individuals and schizophrenia patients. Oral PEA has shown well-documented safety and tolerability in numerous clinical trials with doses 300-1200 mg per day both in healthy and sick populations. Its nature as an endogenous autacoid and essential human diet compound renders PEA nearly devoid of known or potential adverse effects.
- DETAILED DESCRIPTION OF THE PROJECT 2.1. RATIONALE FOR CURRENT STUDY
The main purpose of the present study is to address the absence of an effective treatment for CHR individuals. We will perform an investigator-initiated proof-of-concept study (Phase-2 Pilot Study), with the purpose to examine:
(i) PEA ability to alleviate subtle psychotic and anxiety symptoms in CHR patients; (ii) PEA safety and tolerability; (iii) The biological basis of PEA effect. 2.2. TRIAL OBJECTIVES
To evaluate:
(i) The viability of identifying and consenting CHR patients into a trial with PEA; (ii) The efficacy of PEA in providing relief to attenuated psychotic symptoms (APS) in CHR patients; (iii) Whether sustained PEA treatment is well tolerated by CHR patients over a period of at least 12 weeks; (iv) The biological mechanisms underpinning PEA beneficial effects in CHR patients (e.g., modulation of the endocannabinoid (eCB) system, immunological response, metabolic fingerprinting, gut microbiome composition).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 35 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
结局指标
主要结局
Severity of attenuated psychotic symptoms (APS)
时间窗: 12 weeks for the initial phase, further 24 weeks for the extension phase
Comprehensive Assessment of At-Risk Mental State (CAARMS)
次要结局
- Clinical remission, defined as no longer meeting the APS criteria(12 weeks for the initial phase, further 24 weeks for the extension phase)
- Distress associated with psychotic symptoms(12 weeks for the initial phase, further 24 weeks for the extension phase)
- Severity of anxiety symptoms(12 weeks for the initial phase, further 24 weeks for the extension phase)
- Level of impaired global functioning(12 weeks for the initial phase, further 24 weeks for the extension phase)
- Total CAARMS score(12 weeks for the initial phase, further 24 weeks for the extension phase)