Acute Exercise and NK Cell Regulation in Tissue and Circulation After IL-6R Blockade - a Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- NK cell phenotype in response to acute exercise with or without IL-6R blockade
研究概览
简要总结
The study is a randomized controlled trial studying the acute effect of intense aerobic exercise upon NK (Natural Killer) cell activation and appetite-regulation in human participants with or without concommitant IL-6R receptor blockade (Tocilizumab)
详细描述
Objectives:
Primary Objective:
- To explore the association between acute exercise, IL-6 blockade and NK regulation in circulation.
- To explore whether exercise activated NK-cells have a unique phenotype using single cell RNA sequencing.
Secondary Objectives:
- To explore the effect of acute aerobic exercise on NK cell number and activity in circulation, muscle and adipose tissue, in healthy young males, in order to indirectly explore exercise as an anti-cancer remedy.
- To assess the kinetics of the NK-cell response and, if possible, chronologically investigate the appearance and whereabouts of the activated NK-cells.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
The IL-6R receptor blockade infusion will have bag concealment so that neither the scientific staff or the subject will know if Tocilizumab or saline (placebo) is given and we do not expect the subjects to "feel" the infusion or the results of the infusion.
All scientific staff will be blinded to group allocation using encryption. Only once all data have been obtained (histology, blood analysis, gene-expression, Western Blot, Flow cytometry, single cell RNA sequencing) concealment will be broken so that statistical analysis can be conducted.
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •recreationally active
- •moderately trained
- •healthy young males aged 18-40 years
- •BMI from 18-30 kg·m2
排除标准
- •Cardiovascular disease
- •Rheumatologic disease
- •Metabolic disease,
- •Elite sports or high aerobically training status (VO2max>60ml O2/min/kg),
- •Frequent/chronic use of medications affecting physical performance or inflammation (NSAIDS, DMARDS)
研究组 & 干预措施
BLOCK
This group will do intense aerobic exercise with concomitant IL-6R blockade
干预措施: Tocilizumab Injectable Product (Drug)
CON
This group will do intense aerobic exercise without concomitant IL-6R blockade
干预措施: Saline 0.9% 100 ml NaCl 0.9% will be infused over 1 hour (Other)
结局指标
主要结局
NK cell phenotype in response to acute exercise with or without IL-6R blockade
时间窗: Up to 1 day
Change in NK-cell phenotype using single cell RNA sequencing. Here, within-group changes of baseline vs. post exercise timepoints as well as between group differences between IL-6 blockade and placebo will be investigated. The focus will be on markers of cytotoxicity, cell adhesion and adrenergic signaling.
Kinetics and regulation of NK (Natural Killer) cells during and following acute exercise
时间窗: Up to 1 day
Change in NK cell and NK cell subset count in circulation before and after acute aerobic exercise with or without IL-6R blockade.
次要结局
- Change in circulating IL-6(Up to 1 day)
- Change in circulating IL-2(Up to 1 day)
- Change in NK cell phenotype in adipose tissue(3 hours after intervention)
- Change in NK cell count in adipose tissue(3 hours after intervention)
- Change in NK cell count in muscle tissue(3 hours after intervention)
- Change in NK cell phenotype in muscle tissue(3 hours after intervention)
- Change in macrophage count in muscle tissue(3 hours after intervention)
- Change in macrophage phenotype in muscle tissue(3 hours after intervention)
- Change in macrophage count in adipose tissue(3 hours after intervention)
- Change in macrophage phenotype in adipose tissue(3 hours after intervention)
- Change in T-cell count in adipose tissue(3 hours after intervention)
- Change in T-cell phenotype in adipose tissue(3 hours after intervention)
- Change in T-cell count in muscle tissue(3 hours after intervention)
- Change in T-cell phenotype in muscle tissue(3 hours after intervention)
- Change in monocyte count in circulation(Up to 1 day)
- Change in T-cell count in circulation(Up to 1 day)
- Change in B-cell count in circulation(Up to 1 day)
- Change in IL-6 receptor expression on NK-cells in circulation(Up to 1 day)
- Change in circulating IL-1(Up to 1 day)
- Change in circulating IL-10(Up to 1 day)
- Change in circulating TNF-alpha(Up to 1 day)
- Change in circulating G-CSF(Up to 1 day)
- Change in circulating epinephrine(Up to 1 day)
- Change in circulating norepinephrine(Up to 1 day)
- Change in circulating total leucocytes(Up to 1 day)
- Change in circulating neutrophils(Up to 1 day)
- Change in circulating reticulocytes(Up to 1 day)
- Change in circulating eosinophils(Up to 1 day)
- Change in circulating basofile leucocytes(Up to 1 day)
- Change in circulating lactate(Up to 1 day)
- Change in CRP(Up to 1 day)
- Change in circulating total lymphocytes(Up to 1 day)
- Change in circulating Prolactin(Up to 1 day)
- Change in cortisol(Up to 1 day)
- Change in metamyelocytes(Up to 1 day)
- Change in ACTH(Up to 1 day)
- Change in hsCRP(Up to 1 day)
- Novel myokines during acute exercise(Immediately after acute bout of exercise)
- VO2max(Baseline)
- Lean Body mass(Baseline)
- Fat mass(Baseline)
- Bone Mineral Density(Baseline)
- Appetite assessment(4 hours after intervention)
- Ad libitum caloric intake(4 hours after intervention)
- Gastric emptying(4 hours after intervention)
- Change in GLP1(4 hours after intervention)
- Change in PYY(4 hours after intervention)
- Change in CCK(4 hours after intervention)
- Change in Glucose(4 hours after intervention)
- Change in Insulin(4 hours after intervention)
- Change in C-peptide(4 hours after intervention)
- Change in free fatty acids(4 hours after intervention)
- Change in acetoacetate(4 hours after intervention)
- Change in betahydroxybutyrate(4 hours after intervention)
- Change in CRH(4 hours after intervention)
- Change in AVP(4 hours after intervention)
研究者
Andreas Kraag Kraag Ziegler
Principal Investigator
Rigshospitalet, Denmark