A double- blind randomised placebo-controlled trial of Urolithin-A for deficit symptoms in Schizophrenia: focus on dysfunctional mitophagy
试验速览
- 阶段
- Phase 3 4
- 状态
- 尚未招募
- 发起方
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Change in Negative symptoms (Scale for assessment of Negative symptoms) score and Cognitive deficits (Brief Assessment of Cognition in Schizophrenia) composite score
研究概览
简要总结
Rationale: Schizophrenia affects 10% of India’s population and is a major cause of psychiatric disability. Deficit symptoms, the core cause of disability, are linked to neuroinflammation and oxidative stress. Mitochondrial dysfunction, primarily with impaired mitophagy (self-clearance of damaged mitochondria), leads to cellular dysfunction, energy dysregulation, and inflammation. Therapies targeting mitophagy could address the core pathology. Urolithin A (UA), derived from dietary ellagitannins via gut microbiota, enhances mitophagy and lysosomal health.
Objectives: Evaluate the clinical efficacy of UA supplementation versus placebo in improving deficit symptoms in schizophrenia. To identify theranostic and mechanistic mitochondrial markers of the adjunct UA, in schizophrenia, in-vitro and in-vivo. Methods: In this placebo-controlled trial, 40 of the 80 patients will be randomized to receive 500mg of oral supplementation of UA for three months. Clinical and cognitive outcomes will be assessed along with the blood and brain-magnetic resonance spectroscopy-based mitochondrial markers. Similar data from 40 healthy volunteers will be used to validate biomarkers. The mechanism of UA-mediated mitophagy will be assessed with in-vivo exposures in a subset of participants’ lymphoblastoid cell lines (LCLs) derived from the peripheral blood mononuclear cells (PBMCs).
Expected outcome: This high-risk, high-reward study offers a novel approach to managing deficit symptoms. Its mechanistic and theranostic insights could identify responders early and guide the development of low-cost interventions like dietary ellagitannins and specific UA-synthesising probiotics.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- Participant and Outcome Assessor Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 50.00 Year(s)（—）
- 性别
- All
入选标准
- •a.18-50 years both sexes b.
- •A minimum education level of 8th grade c.
- •Schizophrenia and related disorders as per the diagnostic and statistical manual of mental disorders (DSM5) d.
- •On stable antipsychotic dose for minimum 4 weeks with persistent deficit symptoms defined based on MoCA+DSST and/or SANS (defined below) e.
- •Providing written informed consent.
排除标准
- •Patients with prominent psychotic symptoms [Global item of Scale for Assessment of Positive Symptoms >3 59 ].
- •Patients with any co-morbid neurological/medical disorder, or intellectual disability disorder to the severity that impedes the trial participation c.
- •Current psychoactive substance dependence (except caffeine or nicotine) d.
- •Suicidal risk or psychiatric emergency e.
- •Pregnancy/post-partum period.
结局指标
主要结局
Change in Negative symptoms (Scale for assessment of Negative symptoms) score and Cognitive deficits (Brief Assessment of Cognition in Schizophrenia) composite score
时间窗: from baseline to 3 months of the intervention
次要结局
- Change in SANS score and BACS composite score(from baseline to 1 and 2 months of the intervention)
- Change in other clinical measures (CAINS, SAPS, BPRS, GAF, GSDS, CGI, MedDRA(events and subdomains of BACS))
- Urolithin levels(from baseline to 3 months of the intervention)
- Mitophagy markers, mitochondrial bioenergetics, membrane potentials and Brain MRS markers(from baseline to 3 months of the intervention)
研究者
SREERAJ VS
National Institute of Mental Health and Neuro Sciences (NIMHANS)