Controlled and Randomized Clinical Trial for Evaluating the Effect of a Supplement of Glycine as Adjuvant in the Treatment of COVID-19 Pneumonia in Patients Initiating Mechanical Ventilation
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 59
- 试验地点
- 2
- 主要终点
- Mortality
研究概览
简要总结
This study will explore whether a daily supplement of glycine, a substance that has antiinflammatory, cytoprotective, and endothelium-protecting effects, can improve mortality, as well as clinical and biochemical parameters, in patients with severe COVID-19 who initiate mechanical ventilatory support.
详细描述
Patients with severe forms of COVID-19 often develop acute respiratory distress syndrome (ARDS) associated with high levels of proinflammatory cytokines and damage of lungs and other organs. A special feature in these patients is thrombotic events in the micro- and macro-vasculature. Owing to the lack of a specific and efficient treatment against COVID-19, lowering of this "cytokine storm" is a further proposed strategy.
Glycine is the major agonist of glycine receptors (GlyR), which are chloride channels that hyperpolarize cell membranes of inflammatory cells such as macrophages and neutrophils, turning them less sensitive to proinflammatory stimuli. In addition, glycine possesses a cytoprotective effect, improves endothelial function, and diminishes platelet aggregation.
In laboratory animals, in a rat model of endotoxic shock a 5% glycine-rich diet lowers mortality, reduces pulmonary neutrophilic inflammation and hepatic lesions, and avoids elevation of serum TNF-alpha. In animal models of ischemia-reperfusion injury, glycine protects the gut and lungs.
In in vitro studies, glycine diminishes the expression and release of TNF-alpha and IL-6 from adipose tissue, 3T3-L1 cells, and alveolar macrophages, probably through inhibition of phosphorylation of NF-kappaB. Finally, glycine diminishes platelet aggregation.
In human beings, glycine has been used for many years for the management of some ailments. In diabetic patients, oral glycine reduces glycosylated hemoglobin levels and serum TNF-alpha, and in patients with cystic fibrosis glycine improves the clinical and spirometric status, and tend to lower serum TNF-alpha, IL-6 and G-CSF.
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
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •With COVID-19 confirmed (or awaiting confirmation) by PCR.
- •With a clinical decision of initiation of mechanical ventilation or with <48 h under mechanical ventilation.
- •Informed consent signed by the participant's responsible.
排除标准
- •Pregnant women.
- •Already participating in another research protocol.
- •Elimination Criteria:
- •Voluntary hospital discharge or referenced to another institution.
结局指标
主要结局
Mortality
时间窗: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.
Number of participants who die divided by number of subjects enrolled in the that study group.
次要结局
- Arterial plasma lactate(From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.)
- Serum IL-2(From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.)
- Serum IL-12(From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.)
- Serum MIP-1β(From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.)
- Serum aspartate aminotransferase(From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.)
- Serum alkaline phosphatase(From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.)
- Days under mechanical ventilation(From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.)
- Serum IL-6(From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.)
- Serum IL-1β(From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.)
- Serum IL-7(From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.)
- PaO2/FiO2 ratio(From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.)
- Serum IL-5(From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.)
- Serum IL-8(From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.)
- Hemoglobin(From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.)
- Eosinophils(From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.)
- Basophils(From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.)
- Serum PAI-1(From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.)
- APACHE II score(From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.)
- Serum IL-4(From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.)
- Serum IL-10(From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.)
- Serum IL-13(From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.)
- Serum GM-CSF(From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.)
- Serum MCP-1(From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.)
- Serum total bilirubin(From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.)
- Total leukocytes(From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.)
- Platelets(From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.)
- Prothrombin time(From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.)
- Serum IL-17(From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.)
- Serum G-CSF(From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.)
- Serum IFN-γ(From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.)
- Serum TNF-α(From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.)
- Serum creatinine(From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.)
- Serum alanine aminotransferase(From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.)
- Monocytes(From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.)
- Serum conjugated bilirubin(From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.)
- Neutrophils(From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.)
- Lymphocytes(From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.)
- SOFA score(From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.)
- Serum unconjugated bilirubin(From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.)
- Serum C reactive protein(From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.)
研究者
Mario H. Vargas
Senior Researcher
Instituto Nacional de Enfermedades Respiratorias