Wei Yudong, Zhang Hua, Zhang Shuang, Li Haiyan
Drug Clinical Trial Center, Peking University Third Hospital 49 North Garden Road, Haidian District, Beijing 100191, China.
Research Center of Clinical Epidemiology, Peking University Third Hospital 49 North Garden Road, Haidian District, Beijing 100191, China.
Am J Transl Res. 2019 May 15;11(5):3187-3194. eCollection 2019.
In order to avoid the occurrence of "abnormal liver biochemical tests" caused by diet in Phase I clinical trial, the effect of a low-calorie and low-carbohydrate diet on biochemical indices of liver function of healthy volunteers in a Phase I unit was investigated. A single-centered, non-randomized and parallel-controlled study was designed with 46 healthy subjects consuming two types of diet (24 in the experimental group and 22 in the control group). The diets comprised a balanced normal calorie diet for the control group and a low-calorie and low-carbohydrate diet for the experimental group. All subjects were required to reside on site for 15 consecutive days. Liver biochemical indices such as alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST) were detected on Day-1 (baseline), Day 1, Day 2, Day 3, Day 5, Day 7, Day 9, Day 12, Day 15 and Day 22 (follow-up). There was no significant difference in age, ethnicity, occupation and other demographic data between two groups with balanced baseline. There was no significant difference in ALP between two groups and ALP remained unchanged as a function of time. However, ALT level of the experimental group remained constant as a function of time while ALT level of the control group increased with time and the level was significantly higher than the experimental group after Day 2. The difference between two groups increased with time but decreased on Day 22 as follow-up. After controlling the baseline of AST, AST exhibited a similar trend as ALT. After Day 9, 5%-18% of the patients in the control group showed hepatocyte injury, while no hepatic injury was found in the experimental group. In summary, a low-calorie, low-carbohydrate diet can effectively avoid the occurrence of liver biochemical abnormalities caused by diet in Phase I clinical trials.
为避免在Ⅰ期临床试验中因饮食导致“肝脏生化检查异常”的发生,本研究调查了低热量、低碳水化合物饮食对Ⅰ期病房健康志愿者肝功能生化指标的影响。设计了一项单中心、非随机、平行对照研究,46名健康受试者采用两种饮食方式(实验组24人,对照组22人)。对照组采用均衡的正常热量饮食,实验组采用低热量、低碳水化合物饮食。所有受试者均需连续15天住院。在第-1天(基线)、第1天、第2天、第3天、第5天、第7天、第9天、第12天、第15天和第22天(随访)检测碱性磷酸酶(ALP)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)等肝脏生化指标。两组基线均衡,年龄、种族、职业等人口统计学数据无显著差异。两组间ALP无显著差异,且ALP随时间无变化。然而,实验组的ALT水平随时间保持恒定,而对照组的ALT水平随时间升高,且在第2天后显著高于实验组。两组间差异随时间增加,但在第22天随访时减小。在控制AST基线后,AST呈现与ALT相似的趋势。第9天后,对照组5%-18%的患者出现肝细胞损伤,而实验组未发现肝损伤。综上所述,低热量、低碳水化合物饮食可有效避免Ⅰ期临床试验中因饮食导致的肝脏生化异常的发生。