The Meta-SHIFT Study: How Metabolic Shift Shapes Human Immunometabolism - a Fasting Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 28
- 试验地点
- 2
- 主要终点
- Change in PBMC energy metabolism.
研究概览
简要总结
During fasting, the body shifts from using carbohydrates to relying more on fat as its main source of energy. This process is known as the 'metabolic shift'. Fat tissue helps supply this energy by breaking down stored fat into fatty acids, which are released into the bloodstream and transported to organs throughout the body. In addition to fatty acids, many other substances in the blood (such as metabolites) change during fasting to help maintain normal body function.
Immune cells also circulate in the blood and play an important role in protecting the body against infections and diseases such as cancer. However, it is not yet well understood how the metabolic shift during fasting affects immune cell function. The purpose of this study is to investigate how 24 hours of fasting influences immune cell metabolism and function.
详细描述
Rationale: Fasting leads to changes in metabolism and immune function. However, the specific biological connections between these processes are not fully understood. By studying how fasting affects immune cells, this study aims to clarify the bidirectional relationship between metabolism and immune function.
Objectives: The primary objective is to investigate the impact of fasting on immune cells known as peripheral blood mononuclear cells (PBMCs) in healthy adults. The study will examine four main features of these cells:
- change in basal PBMC energy metabolism;
- change in activated PBMC energy metabolism;
- change in the inflammatory capacity of activated PBMCs; and
- change in PBMC subset abundance.
The secondary objectives are to 1) study how fasting affects PBMC gene expression (whole genome single cell transcriptome) and blood metabolites, 2) identify relationships between changes in metabolites and changes in immune cell function and gene expression, and 3) investigate how fasting-induced changes in gene expression are affected by refeeding. In addition, the explorative objectives are to determine how fasting affects the immune cell population residing in subcutaneous adipose.
Study design: The Meta-SHIFT study is a single-arm intervention study that investigates the effect of fasting by comparing the same subjects 2 hours after meal consumption (fed state or 'baseline') and 24 hours after baseline (fasted state or '24 hours'). Participants will serve as their own control.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Apparently healthy
- •Age 18-40y at the time of recruitment
- •BMI ≥ 18.5 and ≤ 24.9 kg/m2
- •Willing to participate in all study activities during the 3-day intervention
- •Signed informed consent
排除标准
- •Diagnosed with any chronic medical condition that can interfere with the study outcome (e.g., cardiovascular disease, cancer, diabetes mellitus type 1 or 2, liver disease, pulmonary disease, renal disease, inflammatory bowel disease, thyroid disease, long COVID, PASC)
- •Bleeding disorder (e.g., Hemophilia A/B, Von Willebrand Disease, or low platelets), current anemia or current use of blood thinners or anticoagulants (e.g. warfarin, heparin)
- •Any acute or chronic infection disease or fever in the past month
- •Antibiotic use in the past 2 months
- •Use of any prescribed medications (incl. GLP-1 agonists), except for contraceptives
- •Usage of recreational drugs in the last three months
- •Unstable body weight (weight gain or loss >5% of total BW in the past three months)
- •Following any restrictive diet within one month of starting the study (for example a ketogenic diet or weight loss diet)
- •Fasted for 16 hours or longer in the past week
- •History of an eating disorder (e.g., anorexia nervosa, bulimia nervosa, or binge eating disorder)
- •Allergic to one or more components of the standardized meal and/or shake (i.e., milk, wheat, and soy)
- •Average alcohol intake that exceeds 1 consumption/day or 7 consumptions/week over the past month
- •Tobacco smoker or regular use of nicotine products
- •Donated or intend to donate blood from 2 months before the study until the end of the study
- •Being pregnant or lactating
- •Participation in another biomedical study during this study
研究组 & 干预措施
Fasting
26-hour fasting
干预措施: Fasting (Other)
结局指标
主要结局
Change in PBMC energy metabolism.
时间窗: Baseline, 24 hours
Change from baseline PBMC glucose dependence (%) and mitochondrial dependence (%) at 24-hours, as measured by the flow cytometry-based CENCAT method.
Change in activated PBMC energy metabolism.
时间窗: Baseline, 24 hours
Change from baseline activated PBMC glucose dependence (%) and mitochondrial dependence (%) at 24-hours, as measured by the flow cytometry-based CENCAT method. PBMCs are activated in vitro for 2-hours using LPS or TransAct.
Change in inflammatory capacity of activated PBMCs.
时间窗: Baseline, 24 hours
Change from baseline activated PBMC cytokine positive cells (%) and relative cellular cytokine quantity (fluorescent intensity) at 24-hours, as measured by a flow cytometry-based intracellular cytokine stain. PBMCs are activated in vitro for 2-hours using LPS or TransAct.
Change in PBMC subset abundance.
时间窗: Baseline, 24 hours
Change from baseline PBMC subset counts, as assessed with a hematology analyzer.
次要结局
- Change in PBMC transcriptome.(Baseline, 24 hours)
- Change in plasma metabolite profile.(Baseline, 24 hours)
- Change in PBMC RNA expression.(Baseline, 24 hours, 26 hours)