Sensoril® (Ashwagandha), an Immunomodulator and Anti-inflammatory Agent for Schizophrenia: A Parallel Group, Randomized Double Blind, and Placebo Controlled Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 68
- 试验地点
- 1
- 主要终点
- Positive and Negative Syndrome Scale (PANSS)
研究概览
简要总结
Withania somnifera (WSE; Ashwagandha in Ayurveda) extracts have been used as an adaptogen or to build resistance to stress or diseases in indigenous medical systems in India for centuries. Modern scientific data for WSE indicate several bioactive molecules (withanolides, withanosides, indosides, withaferin-A, others) with significant immunomodulatory, anti-inflammatory and stress reducing properties.
This study will examine whether a standardized extract of Withania Somnifera (WSE; Sensoril®) will improve total, positive, negative symptoms, and stress in patients with schizophrenia. The study will examine whether WSE reduces PANSS positive and negative symptoms and stress scores in subjects, and whether these improvements are mediated by changes in inflammatory immune indices. An additional aim will determine if patients receiving WSE will have fewer adjustments to their psychotropic medications that those assigned to placebo. The study will examine whether WSE will re-balance Th1/Th2 ratios (cytokine measures) and mediate a reduction of elevated hs-CRP levels. It is hypothesized that those subjects whose Th1/Th2 ratios normalize will likely have a greater magnitude of clinical improvement versus those subjects whose immune ratios remain unbalanced.
The proposal is a 12-week, double-blind, placebo-controlled RCT of WSE added to antipsychotic medications in approximately 60 or more patients with schizophrenia with an exacerbation of symptoms. If efficacy is affirmed, this low cost extract could be studied further, and used quite readily across low, middle and high income countries.
详细描述
The primary aim is to determine whether a standardized extract of Withania somnifera will reduce psychopathology scores (PANSS total) and stress scores(PSS total) in persons with schizophrenia?
The study will also determine whether WSE reduces measures of positive and negative and general symptoms of schizophrenia (PANSS subscale scores)?
Another primary aim will be to determine if changes in antipsychotic and/or other psychotropic medications (lithium, anticonvulsants, antidepressants, anxiolytic agents or hypnotics) (examples: dosage escalation or reductions or switch or stoppage) will favor the group receiving the standardized Withania somnifera extract versus those receiving placebo. Even though we expect changes in antipsychotic medications to occur when patients experience an exacerbation of psychotic symptoms (or other psychiatric symptoms), we hypothesize that those receiving the standardized Withania somnifera extract will experience fewer medication adjustments then those assigned to placebo.
A secondary aim is to determine whether WSE will rebalance TH1/TH2 ratios (cytokine measures) and mediate a reduction of elevated hs-CRP levels? The study will assess whether those subjects whose TH1/TH2 ratios normalize have a greater magnitude of clinical improvement vs. those subjects whose immune ratios remain unbalanced. Similarly, the study will assess whether reduction of hsCRP levels correlate with improvements in PANSS total and subscale scores or the PSS total scores.
Eighty or more patients with DSM IV TR (or if instituted by the study initiation: DSM V) schizophrenia or schizoaffective disorder will be screened and 60 or more eligible patients will be enrolled in a 12 week placebo controlled double blind study. Subjects who have experienced an exacerbation of positive symptoms (delusions, hallucinations, etc). Subjects receiving medications that affect the immune-inflammatory system will be excluded and those receiving antibiotics, antiviral or anti-parasitic medications will be excluded.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult males or females (≥ 18 years, to 75 years)
- •DSM IV TR diagnosis of schizophrenia or schizoaffective disorder (If officially instituted by study initiation: DSM V diagnoses will be used).
- •Ability to provide informed written consent
- •PANSS total score ≥ 60, positive symptom cluster, (delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, hostility and unusual thought content with at least 2 items scoring ≥ 4, or one of these items scoring ≥ 5, on a scale ranging from 1 = absent to 7 = extreme
- •Current symptom exacerbation ≥ 2 weeks, but ≤ 1 year
- •Receiving anti-psychotic medications for ≥ 4 weeks
- •For women of child bearing age, a negative pregnancy test at screening.
排除标准
- •Testing positive for illicit substances (marijuana or alcohol use will be assessed on a case by case basis, caffeine and nicotine are excepted)
- •Receiving pharmacological treatment for addictions (naltrexone, suboxone, acamprosate, others) will be reviewed on a case by case basis
- •Seriously unstable medical illnesses
- •Pregnant or breast feeding women
- •Known allergy or history of serious adverse event with WSE
- •Subjects who may require imminent hospitalization (examples: suicidal or aggressive behavior)
- •Currently receiving antibiotics, anti-viral, or anti-parasitic medications
- •Currently receiving immunosuppressive medications (e.g. corticosteroids, chemotherapy or transplantation or HIV/AIDs associated drugs).
- •Currently receiving NSAIDs or Aspirin (>81 mg/day) on a daily basis or PRN use > 2x/week (in the last 4 weeks).
研究组 & 干预措施
Sensoril®
Sensoril® is a proprietary extract of Withania Somnifera
干预措施: Sensoril® (Drug)
Placebo
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Positive and Negative Syndrome Scale (PANSS)
时间窗: Baseline and 12 Weeks
The Positive and Negative Syndrome Scale (PANSS) measures symptom severity in patients with psychotic illnesses. It yields a total score as well as subscores for Positive symptoms, Negative symptoms and General symptoms. PANSS Positive subscale consists of 7 Items - (minimum score = 7, maximum score = 49) - Higher values represent a worse outcome. PANSS Negative subscale consists of 7 Items - (minimum score = 7, maximum score = 49) - Higher values represent a worse outcome. General Psychopathology subscale consists of 16 items - (minimum score = 16, maximum score = 112) - Higher values represent a worse outcome. PANSS Total Score - The 3 subscales scores are summed to compute a PANSS Total score. The minimum PANSS total score = 30, maximum = 210 - Higher values represent a worse outcome
次要结局
- Immune Marker IFN-Y (Gamma)(Baseline and 12 weeks or end of study)
- Perceived Stress Scale (PSS)(Baseline and 12 weeks or end of treatment)
- Clinical Global Impression Scale (CGI-S) - Severity(Baseline and 12 weeks or end of study)
- Number of Participants With a Score of 1, 2, or 3 on the Clinical Global Impression Improvement Scale(12 weeks)
- Immune Marker IL-2(Baseline and 12 weeks or end of study)
- Immune Marker IL-4(Baseline and12 weeks or end of study)
- Immune Marker IL-6(Changes from Baseline in Immune markers at 12 weeks or end of study)
- Immune Marker Hs-CRP (High Sensitivity C Reactive Protein)(Baseline and 12 weeks or end of study)
- Immune Marker S-100B(Baseline and 12 weeks or end of treatment)
研究者
K.N. Roy Chengappa
Professor of Psychiatry
University of Pittsburgh