Preoperative Metabolic Optimization: Influence of Intermittent and Buchinger-Type Fasting on the Gut Microbiome, Immune Profile, and Postoperative Complications in Patients Undergoing Primary Total Hip Arthroplasty - A Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 130
- 试验地点
- 1
- 主要终点
- Change in plasma interleukin-8 (IL-8) concentration from baseline to Day +7 post-operatively
研究概览
简要总结
Postoperative complications occur in 5-15% of patients undergoing elective primary total hip arthroplasty (THA), including periprosthetic joint infection (PJI), thrombosis, wound healing disorders, and metabolic dysregulation. The gut microbiome and the systemic immune profile have both been implicated as modifiable contributors to perioperative complication risk. Preoperative therapeutic fasting has been shown to remodel the gut microbiome, lower proinflammatory cytokines, and improve metabolic parameters.
This single-center, prospective, randomized, two-arm controlled trial at Charité - Universitätsmedizin Berlin investigates whether a structured 20-day preoperative fasting intervention (alternating cycles of the Buchinger Fastenbox and intermittent fasting) modulates two co-primary endpoints - plasma IL-8 (a central proinflammatory marker) and gut microbial alpha-diversity (Shannon index) - compared with standard preoperative care. Secondary endpoints include further immune markers (TNFα, IL-10, T-/B-/NK-cell subsets, activation/exhaustion markers, monocyte HLA-DR), microbiome composition and function, continuous glucose-monitoring and daily metabolic measures, patient-reported outcomes (HOOS, PROMIS-33, infection self-report), and clinical outcomes (postoperative complications per EBJIS criteria, length of stay).
Adults aged 18-75 undergoing elective primary THA are stratified by metabolic status (metabolically healthy vs. metabolically unhealthy according to harmonized metabolic-syndrome criteria) and randomized 1:1 to the fasting intervention versus standard care. Stool and whole-blood samples are collected at baseline (Day -21), and at Day +7 post-operatively for shotgun-metagenomic sequencing and multiparameter flow cytometry, with additional cytokine blood samples at Day -1 and 6 h / 24 h / 72 h post-operatively. Continuous glucose monitoring is performed in all participants from Day -21 until surgery. Planned enrollment is 130 participants.
详细描述
Background. Periprosthetic joint infection (PJI) and other postoperative complications after THA carry substantial clinical and economic costs. Recent evidence links the gut microbiome and systemic immune homeostasis to perioperative complication risk, and preoperative caloric restriction has been shown to lower proinflammatory cytokines and shift gut microbial composition toward a less inflammatory profile.
Hypotheses. Primary: A structured 20-day preoperative fasting intervention reduces plasma IL-8 and increases gut microbial alpha-diversity (Shannon index) at Day +7 post-operatively compared with standard preoperative care.
Secondary (exploratory): Fasting modulates broader immune (TNFα, IL-10, immune-cell subsets, activation/exhaustion markers, HLA-DR) and microbiome (taxonomic, functional) parameters, improves metabolic indicators captured by continuous glucose monitoring and daily measures, and reduces postoperative complications, patient-reported infection symptoms, and length of stay.
Design. Single-center, prospective, two-arm, parallel-group, randomized, open-label controlled trial. Randomization is stratified by metabolic status (metabolically healthy vs. metabolically unhealthy per harmonized metabolic-syndrome criteria, Alberti et al. 2009). Planned enrollment: n = 130 (65 per arm; balanced across metabolic strata).
Intervention (Fasting arm). Structured 20-day preoperative fasting schedule self-administered at home with study-team supervision:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults aged 18-75 years (inclusive)
- •Scheduled for elective primary total hip arthroplasty (THA)
- •Able and willing to provide written informed consent
- •Able to follow the 20-day preoperative fasting protocol independently at home (if randomized to the fasting arm) or willing to be randomized to either arm
排除标准
- •Resorption disorder due to bowel disease (e.g. inflammatory bowel disease, short-bowel syndrome, active celiac disease)
- •Antibiotic therapy within the last 2 months before baseline (T0)
- •Probiotic, prebiotic, or symbiotic supplementation within the last 2 months before baseline (T0)
- •Inability or unwillingness to provide informed consent
- •Severe comorbidity precluding fasting (e.g. ASA ≥ IV, advanced renal/hepatic impairment, eating disorder)
- •BMI < 18.5 kg/m² (underweight)
- •Concurrent participation in another interventional drug or device trial
- •Pregnancy or breastfeeding
研究组 & 干预措施
Preoperative Fasting (20 days; Buchinger Fastenbox + intermittent fasting)
Adults aged 18-75 scheduled for elective primary total hip arthroplasty follow a structured 20-day preoperative fasting schedule self-administered at home with study-team supervision. Schedule: Day -20 to -16 - Buchinger Fastenbox (5 days); Day -15 to -11 - intermittent fasting (5 days); Day -10 to -6 - Buchinger Fastenbox (5 days); Day -5 to -1 - intermittent fasting (5 days). No fasting is performed post-operatively. Daily self-monitored ketones, weight, waist circumference, and blood pressure are recorded throughout the fasting window. All other perioperative care follows the standard institutional protocol.
干预措施: Buchinger Fastenbox + intermittent fasting (20-day preoperative schedule) (Other)
Standard Preoperative Care
Adults aged 18-75 scheduled for elective primary total hip arthroplasty receive routine preoperative care according to the institutional standard at Charité Centrum für Muskuloskeletale Chirurgie. No fasting protocol is provided as part of the study. Continuous glucose monitoring and daily weight, waist circumference, and blood pressure are recorded during the same pre-operative window as the fasting arm. Stool and blood samples are collected at the same study time points as the fasting arm.
结局指标
主要结局
Change in plasma interleukin-8 (IL-8) concentration from baseline to Day +7 post-operatively
时间窗: Baseline (Day -21, before start of intervention) and Day +7 post-operatively
IL-8 plasma concentration (pg/mL), measured by validated immunoassay
Change in gut microbial alpha-diversity (Shannon index) from baseline to Day +7 post-operatively
时间窗: Baseline (Day -21, before start of intervention) and Day +7 post-operatively
Shannon diversity index from shotgun-metagenomic stool sequencing
次要结局
- Perioperative kinetics of plasma cytokines (TNFα, IL-10, IL-6, IL-8)(Baseline (Day -21), Day -1 pre-op, and 6 h, 24 h, 72 h, and Day +7 post-operatively)
- Serum C-reactive protein (CRP)(Baseline (Day -21) and Day +7 post-operatively)
- T-cell subsets (CD3+, CD4+, CD8+) by flow cytometry(Baseline (Day -21) and Day +7 post-operatively)
- B-cell frequency (CD19+)(Baseline (Day -21) and Day +7 post-operatively)
- NK-cell frequency (CD16+/CD56+)(Baseline (Day -21) and Day +7 post-operatively)
- T-cell activation / exhaustion markers (CD28, CD57, HLA-DR, PD-1)(Baseline (Day -21) and Day +7 post-operatively)
- Monocyte HLA-DR expression (mHLA-DR)(Baseline (Day -21) and Day +7 post-operatively)
- Neutrophil-to-lymphocyte ratio (NLR)(Baseline (Day -21) and Day +7 post-operatively)
- Gut microbial beta-diversity(Baseline (Day -21) and Day +7 post-operatively)
- Differential microbial abundance(Baseline (Day -21) and Day +7 post-operatively)
- Microbial functional gene profile(Baseline (Day -21) and Day +7 post-operatively)
- Continuous glucose monitoring (CGM) metrics(Day -21 to day of surgery (continuous))
- Daily self-monitored ketones (fasting arm)(Day -20 to day of surgery)
- Daily body weight(Day -20 to day of surgery, then Week 6, Month 3, Month 6 post-operatively)
- Daily waist circumference(Day -20 to day of surgery)
- Daily blood pressure(Day -20 to day of surgery)
- PROMIS-33 patient-reported outcomes(Baseline (Day -21), Week 6, Month 3, Month 6 post-operatively)
- Dietary intake (DEGS1 food frequency questionnaire)(Baseline (Day -21))
- Patient-reported postoperative infection symptoms (study-specific questionnaire)(Weekly from Day +1 to Week 6 post-operatively)
- Postoperative infectious complications (EBJIS)(Day 0 to Day 90 after surgery)
- Wound healing disorders(Day 0 to Day 90 after surgery)
- Reoperation rate(Day 0 to Day 90 after surgery)
- Length of hospital stay (LOS)(From day of surgery to day of discharge (assessed up to 30 days))
- Metabolic complications(Day 0 to Day 30 after surgery)
- Hip disability and Osteoarthritis Outcome Score (HOOS)(Baseline (Day -21), Week 6, Month 3, Month 6 post-operatively)
- Patient-Reported Outcomes Measurement Information System 33-item Profile (PROMIS-33)(Baseline (Day -21), Week 6, Month 3, Month 6 post-operatively)
研究者
Dr. med. Nele Wagener
Principal Investigator
Charite University, Berlin, Germany