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Preoperative Fasting and the Gut Microbiome Before Hip Replacement (PreFAST-Hip)

11. Juni 2026 aktualisiert von: Dr. med. Nele Wagener, Charite University, Berlin, Germany

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

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.

Studienübersicht

Status

Rekrutierung

Bedingungen

Intervention / Behandlung

Detaillierte Beschreibung

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:

  • Day -20 to Day -16 (5 days): Buchinger Fastenbox - ready-to-use organic vegetable broths, low carbohydrate, designed to facilitate ketogenic metabolic switch.
  • Day -15 to Day -11 (5 days): Intermittent fasting (time-restricted feeding).
  • Day -10 to Day -6 (5 days): Buchinger Fastenbox (second cycle).
  • Day -5 to Day -1 (5 days): Intermittent fasting (second cycle). No fasting is performed post-operatively.

Control arm. Standard preoperative care per institutional protocol; no fasting and no probiotic, prebiotic, or symbiotic supplementation as part of the study.

Specimen collection and assessments.

  • Day -21 (baseline / T0): stool + whole-blood sampling for shotgun-metagenomic sequencing, FACS immunophenotyping, and cytokine panel. Start of continuous glucose monitoring (CGM, all participants). Baseline questionnaires: DEGS1 food frequency questionnaire, HOOS, PROMIS-33, and a study-specific infection-baseline questionnaire.
  • Day -20 onward (fasting arm only): daily self-monitored urinary or capillary ketones.
  • Day -20 to surgery (all participants): daily body weight, waist circumference, blood pressure.
  • Day -1 (immediately pre-op): blood sample for cytokine panel.
  • 6 h, 24 h, and 72 h post-operatively: blood samples for cytokine panel.
  • Day +7 post-operatively: stool + whole-blood sampling for shotgun metagenomics, FACS immunophenotyping, and cytokine panel (primary endpoint readout).
  • Weekly to Week 6 post-operatively: study-specific patient-reported infection questionnaire.
  • Week 6, Month 3, Month 6 post-operatively: HOOS, PROMIS-33, body weight.

Analyses. Stool: shotgun metagenomic sequencing (Illumina NovaSeq 6000) with bioinformatic processing (Trimmomatic, DIAMOND, QIIME, Centrifuge, MetaPhlAn/HUMAnN, LEfSe). Blood: multiparameter flow cytometry (CD3, CD4, CD8, CD16/56, CD19, plus CD28, CD57, HLA-DR, PD-1) and standard inflammatory chemistry (CRP, IL-6, IL-8, IL-10, TNFα).

Statistics. Two co-primary endpoints (IL-8, alpha-diversity) tested with a fixed-sequence (gatekeeping) procedure: IL-8 first at α=0.05 two-sided; if significant, alpha-diversity is then tested at α=0.05. Linear mixed models or generalized estimating equations are used to model time × group interactions for repeated measures. Microbiome differential abundance: ANCOM/DESeq2 with covariate adjustment (BMI, age, sex). Multiple testing controlled with FDR. Clinical secondary endpoints are analyzed descriptively.

Studientyp

Interventionell

Einschreibung (Geschätzt)

130

Phase

  • Unzutreffend

Kontakte und Standorte

Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.

Studienkontakt

Studienorte

  • Deutschland
    • State of Berlin
      • Berlin, State of Berlin, Deutschland, 10117
        • Rekrutierung
        • Centrum für Muskuloskeletale Chirurgie (CMSC), Charité - Universitätsmedizin Berlin
        • Kontakt:

Teilnahmekriterien

Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.

Zulassungskriterien

Studienberechtigtes Alter

  • Erwachsene
  • Älterer Erwachsener

Akzeptiert gesunde Freiwillige

Nein

Beschreibung

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Studienplan

Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.

Wie ist die Studie aufgebaut?

Designdetails

  • Hauptzweck: Verhütung
  • Zuteilung: Zufällig
  • Interventionsmodell: Parallele Zuordnung
  • Maskierung: Keine (Offenes Etikett)

Waffen und Interventionen

Teilnehmergruppe / Arm
Intervention / Behandlung
Experimental: 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.
Sonstiges: Buchinger Fastenbox + intermittent fasting (20-day preoperative schedule)
Two 5-day cycles of the Buchinger Wilhelmi Fastenbox (hypocaloric, low-carbohydrate, plant-based vegetable broths) alternating with two 5-day cycles of intermittent fasting (time-restricted feeding), totaling 20 days immediately preceding surgery. Self-administered at home; participants receive structured instructions, daily symptom and metabolic logs, and contact options with the study team for the duration of each cycle.
Kein Eingriff: 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.

Was misst die Studie?

Primäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Change in plasma interleukin-8 (IL-8) concentration from baseline to Day +7 post-operatively
Zeitfenster: Baseline (Day -21, before start of intervention) and Day +7 post-operatively
IL-8 plasma concentration (pg/mL), measured by validated immunoassay
Baseline (Day -21, before start of intervention) and Day +7 post-operatively
Change in gut microbial alpha-diversity (Shannon index) from baseline to Day +7 post-operatively
Zeitfenster: Baseline (Day -21, before start of intervention) and Day +7 post-operatively
Shannon diversity index from shotgun-metagenomic stool sequencing
Baseline (Day -21, before start of intervention) and Day +7 post-operatively

Sekundäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Perioperative kinetics of plasma cytokines (TNFα, IL-10, IL-6, IL-8)
Zeitfenster: Baseline (Day -21), Day -1 pre-op, and 6 h, 24 h, 72 h, and Day +7 post-operatively
Serial plasma concentrations of TNFα, IL-10, IL-6, and IL-8 measured by validated immunoassays.
Baseline (Day -21), Day -1 pre-op, and 6 h, 24 h, 72 h, and Day +7 post-operatively
Serum C-reactive protein (CRP)
Zeitfenster: Baseline (Day -21) and Day +7 post-operatively
Serum CRP concentration (mg/L).
Baseline (Day -21) and Day +7 post-operatively
T-cell subsets (CD3+, CD4+, CD8+) by flow cytometry
Zeitfenster: Baseline (Day -21) and Day +7 post-operatively
Absolute and relative frequencies of CD3+, CD4+, and CD8+ T cells in whole blood.
Baseline (Day -21) and Day +7 post-operatively
B-cell frequency (CD19+)
Zeitfenster: Baseline (Day -21) and Day +7 post-operatively
Frequency of CD19+ B cells.
Baseline (Day -21) and Day +7 post-operatively
NK-cell frequency (CD16+/CD56+)
Zeitfenster: Baseline (Day -21) and Day +7 post-operatively
Frequency of CD16+/CD56+ natural killer cells.
Baseline (Day -21) and Day +7 post-operatively
T-cell activation / exhaustion markers (CD28, CD57, HLA-DR, PD-1)
Zeitfenster: Baseline (Day -21) and Day +7 post-operatively
Frequencies of CD28-, CD57+, HLA-DR+, and PD-1+ T-cell subpopulations.
Baseline (Day -21) and Day +7 post-operatively
Monocyte HLA-DR expression (mHLA-DR)
Zeitfenster: Baseline (Day -21) and Day +7 post-operatively
Median fluorescence intensity of HLA-DR on circulating monocytes.
Baseline (Day -21) and Day +7 post-operatively
Neutrophil-to-lymphocyte ratio (NLR)
Zeitfenster: Baseline (Day -21) and Day +7 post-operatively
NLR derived from differential blood count.
Baseline (Day -21) and Day +7 post-operatively
Gut microbial beta-diversity
Zeitfenster: Baseline (Day -21) and Day +7 post-operatively
Bray-Curtis and weighted UniFrac dissimilarity between time points, analyzed with PERMANOVA.
Baseline (Day -21) and Day +7 post-operatively
Differential microbial abundance
Zeitfenster: Baseline (Day -21) and Day +7 post-operatively
Differential abundance of bacterial taxa at genus and species level between arms (ANCOM/DESeq2 with covariate adjustment).
Baseline (Day -21) and Day +7 post-operatively
Microbial functional gene profile
Zeitfenster: Baseline (Day -21) and Day +7 post-operatively
Functional gene profiling (HUMAnN) including CAZyme abundance and SCFA-related pathways.
Baseline (Day -21) and Day +7 post-operatively
Continuous glucose monitoring (CGM) metrics
Zeitfenster: Day -21 to day of surgery (continuous)
Mean interstitial glucose, glucose variability (SD, CV), time-in-range (70-180 mg/dL) derived from a continuous glucose monitor worn from Day -21 until surgery, compared between arms.
Day -21 to day of surgery (continuous)
Daily self-monitored ketones (fasting arm)
Zeitfenster: Day -20 to day of surgery
Daily urinary or capillary ketone measurements during the 20-day fasting window.
Day -20 to day of surgery
Daily body weight
Zeitfenster: Day -20 to day of surgery, then Week 6, Month 3, Month 6 post-operatively
Daily self-measured body weight (kg) during the preoperative window, and at follow-up (Week 6, Month 3, Month 6).
Day -20 to day of surgery, then Week 6, Month 3, Month 6 post-operatively
Daily waist circumference
Zeitfenster: Day -20 to day of surgery
Daily self-measured waist circumference (cm) during the preoperative window.
Day -20 to day of surgery
Daily blood pressure
Zeitfenster: Day -20 to day of surgery
Daily self-measured systolic and diastolic blood pressure (mmHg) during the preoperative window.
Day -20 to day of surgery
Hip disability and Osteoarthritis Outcome Score (HOOS)
Zeitfenster: Baseline (Day -21), Week 6, Month 3, Month 6 post-operatively
Validated patient-reported hip-specific outcome score; change from baseline to each follow-up time point.
Baseline (Day -21), Week 6, Month 3, Month 6 post-operatively
PROMIS-33 patient-reported outcomes
Zeitfenster: Baseline (Day -21), Week 6, Month 3, Month 6 post-operatively
Validated multi-domain patient-reported outcomes (PROMIS-33); change from baseline to each follow-up time point.
Baseline (Day -21), Week 6, Month 3, Month 6 post-operatively
Dietary intake (DEGS1 food frequency questionnaire)
Zeitfenster: Baseline (Day -21)
Habitual dietary intake captured at baseline using the DEGS1 food-frequency questionnaire.
Baseline (Day -21)
Patient-reported postoperative infection symptoms (study-specific questionnaire)
Zeitfenster: Weekly from Day +1 to Week 6 post-operatively
Study-specific questionnaire on infection-relevant signs and symptoms, completed weekly by the patient during the first 6 weeks post-operatively.
Weekly from Day +1 to Week 6 post-operatively
Postoperative infectious complications (EBJIS)
Zeitfenster: Day 0 to Day 90 after surgery
Incidence of periprosthetic joint infection per EBJIS criteria within 90 days post-operatively.
Day 0 to Day 90 after surgery
Wound healing disorders
Zeitfenster: Day 0 to Day 90 after surgery
Incidence of any wound healing disorder requiring intervention within 90 days post-operatively.
Day 0 to Day 90 after surgery
Reoperation rate
Zeitfenster: Day 0 to Day 90 after surgery
Incidence of reoperation related to the index joint within 90 days post-operatively.
Day 0 to Day 90 after surgery
Length of hospital stay (LOS)
Zeitfenster: From day of surgery to day of discharge (assessed up to 30 days)
Length of inpatient stay for the index admission, in days.
From day of surgery to day of discharge (assessed up to 30 days)
Metabolic complications
Zeitfenster: Day 0 to Day 30 after surgery
Incidence of postoperative metabolic complications (hyper-/hypoglycemia, electrolyte imbalance, sarcopenia risk markers).
Day 0 to Day 30 after surgery

Mitarbeiter und Ermittler

Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.

Sponsor

Charite University, Berlin, Germany

Mitarbeiter

Schulthess Klinik
Buchinger Wilhelmi Clinic

Publikationen und hilfreiche Links

Die Bereitstellung dieser Publikationen erfolgt freiwillig durch die für die Eingabe von Informationen über die Studie verantwortliche Person. Diese können sich auf alles beziehen, was mit dem Studium zu tun hat.

Allgemeine Veröffentlichungen

Studienaufzeichnungsdaten

Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.

Haupttermine studieren

Studienbeginn (Tatsächlich)

1. Juli 2025

Primärer Abschluss (Geschätzt)

1. September 2026

Studienabschluss (Geschätzt)

31. Dezember 2026

Studienanmeldedaten

Zuerst eingereicht

11. Juni 2026

Zuerst eingereicht, das die QC-Kriterien erfüllt hat

11. Juni 2026

Zuerst gepostet (Tatsächlich)

16. Juni 2026

Studienaufzeichnungsaktualisierungen

Letztes Update gepostet (Tatsächlich)

16. Juni 2026

Letztes eingereichtes Update, das die QC-Kriterien erfüllt

11. Juni 2026

Zuletzt verifiziert

1. Juni 2026

Mehr Informationen

Begriffe im Zusammenhang mit dieser Studie

Schlüsselwörter

Zusätzliche relevante MeSH-Bedingungen

Andere Studien-ID-Nummern

  • EA1/279/24

Plan für individuelle Teilnehmerdaten (IPD)

Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?

NEIN

Beschreibung des IPD-Plans

Aggregated and de-identified data will be made available through peer-reviewed publications. Individual participant data will not be shared due to data-protection requirements under the Berliner Datenschutzgesetz (BlnDSG) and the EU GDPR.

Arzneimittel- und Geräteinformationen, Studienunterlagen

Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt

Nein

Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt

Nein

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