NCT04054973撤回2 期
An Open-label Feasibility Trial of Adjunctive L-arginine and Tetrahydrobiopterin Combination in Patients With Treatment Resistant Schizophrenia
University of Massachusetts, Worcester1 个研究点 分布在 1 个国家开始时间: 2019年9月11日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 发起方
- 试验地点
- 1
- 主要终点
- Incidence of Treatment-Emergent Adverse Events as assessed by patient report
研究概览
简要总结
The purpose of this research is to see if daily combination treatment of L-arginine and Kuvan changes brain chemistry in people experiencing schizophrenia as measured by MRS brain scans.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males or Females aged 18-65 years inclusive.
- •English speaking.
- •Primary diagnosis of Schizophrenia established by a structured psychiatric evaluation (MINI) based on Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-V) criteria.
- •Written informed consent in compliance with 21 CFR part 50 and in accordance with the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines.
- •A Positive and Negative Syndrome Scale (PANSS) (Kay et al 1987) total score ≥ 70 with a score of > 4 on two or more of the following PANSS items: delusions, conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content.
- •A score of ≥4 on the Clinical Global Impression-Severity (CGI-S) (Guy, 1976).
- •Must have ongoing antipsychotic treatment for at least 8 weeks, with a stable dose for at least 4 weeks. Antipsychotic medication will not be modified by the research team during the subject's enrollment or participation.
- •Subjects who have failed to achieve clinically-recognized symptom reduction to at least 1 marketed antipsychotic agent, given at a Physician Desk Reference (PDR)-defined therapeutic dose for ≥ 8 weeks during the past 12 months, will be eligible.
- •Women of childbearing potential must have a negative pregnancy test performed at screening visit prior to randomization. Women enrolled in this trial must use adequate birth control.
- •Understands and is able, willing, and (in the opinion of the investigator) likely to fully comply with the study procedures and restrictions.
排除标准
- •Subjects with a history of renal insufficiency, congestive heart failure, cardiac arrhythmias or history of myocardial infarction, liver cirrhosis, guanidinoacetate methyltransferase deficiency, herpes.
- •Subjects who are non-English speaking.
- •Subjects with any clinically significant abnormalities as determined by medical history, physical exam, clinical and lab evaluation suggestive of an underlying disease state that may, in the opinion of the investigator, confound the results of study, increase risk to the subject, or lead to difficulty complying with the protocol.
- •Subjects with the lab values defined as exclusionary safety values in Table
- •On medications known to inhibit folate metabolism (e.g., methotrexate).
- •On medications known to affect NO-mediated vaso-relaxation (e.g., PDE-5 inhibitors such as sildenafil, vardenafil, or tadalafil).
- •Subjects on nitrates.
- •Subjects on levodopa.
- •Subjects on antihypertensive medications (such as ACE inhibitors, angiotensin receptor blockers, isoproterenol, potassium-sparing diuretics).
- •Subjects on antidiabetes medications.
- •Subjects on anticoagulant/antiplatelet medications.
- •Subjects with a current (within the last 3 months) DSM-V diagnosis of alcohol or substance use disorder (excluding nicotine and caffeine) as established by the clinical assessment (MINI) at the screening visit will be excluded.
- •Tested positive for the urine drug screen.
- •Subjects at imminent risk of suicide or injury to self or others, as per the opinion of the investigator, or history of significant suicide attempt within the last 6 months as per the Columbia Suicide Severity Rating Scale (C-SSRS).
- •Subjects that have taken an investigational drug or taken part in a clinical trial within 30 days prior to screening.
- •Known history of phenylketonuria (PKU).
- •Known hypersensitivity reactions (such as anaphylaxis and rash) to L-arginine and/or BH
- •Any other reason that, in the opinion of the investigator, would compromise patient safety or integrity of the study.
研究组 & 干预措施
L-arginine and Kuvan
Experimental
Open-label single arm study, all participants will be in this group
干预措施: L-arginine (Drug)
L-arginine and Kuvan
Experimental
Open-label single arm study, all participants will be in this group
干预措施: Sapropterin Dihydrochloride (Drug)
结局指标
主要结局
Incidence of Treatment-Emergent Adverse Events as assessed by patient report
时间窗: 14-days
The study doctor in conjunction with the study coordinator will conduct a diagnostic interview with the subject at each visit to record the incidence of treatment-emergent adverse events as assessed by patient report.
Changes in brain chemistry as measured by 1H-MRS scans
时间窗: 14 days
To demonstrate that L-arginine and tetrahydrobiopterin (BH4) combination targets and alters brain chemistry in patients with TRS (target engagement). The investigators hypothesize that two-week treatment of L-arginine and Tetrahydrobiopterin (as Kuvan) will alter glutamate and GABA levels measured with proton magnetic resonance spectroscopy (1H-MRS).
次要结局
- Change in blood levels of Tumor Necrosis Factor (TNF-α) from baseline to day 14.(14 days)
- Evaluate changes in NO bioavailability in breath from Baseline to Day 14(14 days)
- Change in blood levels of high-sensitivity C reactive protein (hsCRP) from baseline to day 14.(14 days)
- Change in Positive and Negative Symptom scale (PANSS) from Baseline to Day 14(14 days)
- Change in blood levels of glutathione (GSH) from baseline to day 14.(14 days)
研究者
Xiaoduo Fan
Director, Psychotic Disorders Program
University of Massachusetts, Worcester
研究点 (1)
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