Hip OsteoarthritisPreFAST-HipNCT07651462
Preoperative Fasting and the Gut Microbiome Before Hip Replacement
A study testing Buchinger Fastenbox + intermittent fasting (20-day preoperative schedule) in people with Hip Osteoarthritis and Arthroplasty, Replacement, Hip, run by Charite University, Berlin, Germany at 1 site in Germany.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hip Osteoarthritis, Arthroplasty, Replacement, Hip, Postoperative Complications
- What is being tested?
- Buchinger Fastenbox + intermittent fasting (20-day preoperative schedule)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 130 participants
- Where
- 1 siteGermany
- Study dates
- 1 Jul 2025to 31 Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Germany1 site, 1 recruiting
- Recruiting
Centrum für Muskuloskeletale Chirurgie (CMSC), Charité - Universitätsmedizin Berlin
Berlin, State of Berlin, 10117
Nele Wagener, Dr. med., +49 30 450 615076, nele.wagener@charite.de
About this study
Official title: 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.
Read the detailed description
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.
- Conditions
- Hip Osteoarthritis, Arthroplasty, Replacement, Hip, Postoperative Complications, Surgical Wound Infection, Gastrointestinal Microbiome
- Being tested
- Buchinger Fastenbox + intermittent fasting (20-day preoperative schedule)
- Keywords
- Therapeutic fasting, Buchinger fasting, Intermittent fasting, Gut microbiome, Immunophenotyping, Continuous glucose monitoring, Total hip arthroplasty, Metabolic syndrome, Preoperative optimization
- Medical subject headings
- Osteoarthritis, Hip, Postoperative Complications, Surgical Wound Infection, Intermittent Fasting, Metabolic Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Buchinger Fastenbox + intermittent fasting (20-day preoperative schedule)Other
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.
| Study group | Role | What they receive |
|---|---|---|
| Preoperative Fasting (20 days; Buchinger Fastenbox + intermittent fasting) | Experimental | 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. Receives: Other: Buchinger Fastenbox + intermittent fasting (20-day preoperative schedule) |
| Standard Preoperative Care | No intervention | 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in plasma interleukin-8 (IL-8) concentration from baseline to Day +7 post-operatively
IL-8 plasma concentration (pg/mL), measured by validated immunoassay
Measured: 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
Shannon diversity index from shotgun-metagenomic stool sequencing
Measured: Baseline (Day -21, before start of intervention) and Day +7 post-operatively
Secondary outcomes (25)
Perioperative kinetics of plasma cytokines (TNFα, IL-10, IL-6, IL-8)
Serial plasma concentrations of TNFα, IL-10, IL-6, and IL-8 measured by validated immunoassays.
Measured: Baseline (Day -21), Day -1 pre-op, and 6 h, 24 h, 72 h, and Day +7 post-operatively
Serum C-reactive protein (CRP)
Serum CRP concentration (mg/L).
Measured: Baseline (Day -21) and Day +7 post-operatively
T-cell subsets (CD3+, CD4+, CD8+) by flow cytometry
Absolute and relative frequencies of CD3+, CD4+, and CD8+ T cells in whole blood.
Measured: Baseline (Day -21) and Day +7 post-operatively
B-cell frequency (CD19+)
Frequency of CD19+ B cells.
Measured: Baseline (Day -21) and Day +7 post-operatively
NK-cell frequency (CD16+/CD56+)
Frequency of CD16+/CD56+ natural killer cells.
Measured: Baseline (Day -21) and Day +7 post-operatively
T-cell activation / exhaustion markers (CD28, CD57, HLA-DR, PD-1)
Frequencies of CD28-, CD57+, HLA-DR+, and PD-1+ T-cell subpopulations.
Measured: Baseline (Day -21) and Day +7 post-operatively
Monocyte HLA-DR expression (mHLA-DR)
Median fluorescence intensity of HLA-DR on circulating monocytes.
Measured: Baseline (Day -21) and Day +7 post-operatively
Neutrophil-to-lymphocyte ratio (NLR)
NLR derived from differential blood count.
Measured: Baseline (Day -21) and Day +7 post-operatively
Gut microbial beta-diversity
Bray-Curtis and weighted UniFrac dissimilarity between time points, analyzed with PERMANOVA.
Measured: Baseline (Day -21) and Day +7 post-operatively
Differential microbial abundance
Differential abundance of bacterial taxa at genus and species level between arms (ANCOM/DESeq2 with covariate adjustment).
Measured: Baseline (Day -21) and Day +7 post-operatively
Microbial functional gene profile
Functional gene profiling (HUMAnN) including CAZyme abundance and SCFA-related pathways.
Measured: Baseline (Day -21) and Day +7 post-operatively
Continuous glucose monitoring (CGM) metrics
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.
Measured: Day -21 to day of surgery (continuous)
Daily self-monitored ketones (fasting arm)
Daily urinary or capillary ketone measurements during the 20-day fasting window.
Measured: Day -20 to day of surgery
Daily body weight
Daily self-measured body weight (kg) during the preoperative window, and at follow-up (Week 6, Month 3, Month 6).
Measured: Day -20 to day of surgery, then Week 6, Month 3, Month 6 post-operatively
Daily waist circumference
Daily self-measured waist circumference (cm) during the preoperative window.
Measured: Day -20 to day of surgery
Daily blood pressure
Daily self-measured systolic and diastolic blood pressure (mmHg) during the preoperative window.
Measured: Day -20 to day of surgery
Hip disability and Osteoarthritis Outcome Score (HOOS)
Validated patient-reported hip-specific outcome score; change from baseline to each follow-up time point. HOOS subscale scores range from 0 to 100, with 0 indicating extreme hip symptoms/worst outcome and 100 indicating no hip symptoms/best outcome. Higher scores indicate a better outcome.
Measured: Baseline (Day -21), Week 6, Month 3, Month 6 post-operatively
Patient-Reported Outcomes Measurement Information System 33-item Profile (PROMIS-33)
Validated multi-domain patient-reported outcomes (PROMIS-33); change from baseline to each follow-up time point. ROMIS-33 is reported as domain-specific T-scores plus a pain intensity item. Domain T-score ranges are: Physical Function 22.5-57.0; Anxiety 40.3-81.6; Depression 41.0-79.4; Fatigue 33.7-75.8; Sleep Disturbance 32.0-73.3; Ability to Participate in Social Roles and Activities 27.5-64.2; Pain Interference 41.6-75.6; Cognitive Function 25.0-61.1. Pain Intensity ranges from 0 to 10. Higher scores indicate a better outcome for Physical Function, Ability to Participate in Social Roles and Activities, and Cognitive Function, and a worse outcome for Anxiety, Depression, Fatigue, Sleep Disturbance, Pain Interference, and Pain Intensity.
Measured: Baseline (Day -21), Week 6, Month 3, Month 6 post-operatively
Dietary intake (DEGS1 food frequency questionnaire)
Habitual dietary intake captured at baseline using the DEGS1 food-frequency questionnaire.
Measured: Baseline (Day -21)
Patient-reported postoperative infection symptoms (study-specific questionnaire)
Study-specific questionnaire on infection-relevant signs and symptoms, completed weekly by the patient during the first 6 weeks post-operatively.
Measured: Weekly from Day +1 to Week 6 post-operatively
Postoperative infectious complications (EBJIS)
Incidence of periprosthetic joint infection per EBJIS criteria within 90 days post-operatively.
Measured: Day 0 to Day 90 after surgery
Wound healing disorders
Incidence of any wound healing disorder requiring intervention within 90 days post-operatively.
Measured: Day 0 to Day 90 after surgery
Reoperation rate
Incidence of reoperation related to the index joint within 90 days post-operatively.
Measured: Day 0 to Day 90 after surgery
Length of hospital stay (LOS)
Length of inpatient stay for the index admission, in days.
Measured: From day of surgery to day of discharge (assessed up to 30 days)
Metabolic complications
Incidence of postoperative metabolic complications (hyper-/hypoglycemia, electrolyte imbalance, sarcopenia risk markers).
Measured: Day 0 to Day 30 after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2026
- Study start1 Jul 2025
- Primary completion1 Sep 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Hip OsteoarthritisStudies of the same condition, open and under way.
- More trials run by Charite University, Berlin, GermanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Two-arm parallel-group design with 1:1 randomization stratified by metabolic status (metabolically healthy vs. metabolically unhealthy according to harmonized metabolic-syndrome criteria). Within each stratum, patients are randomized 1:1 to the structured 20-day preoperative fasting intervention versus standard preoperative care.
- Masking
- None (open label)
- Enrolment
- 130 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Charite University, Berlin, Germany
- Sponsor type
- University, hospital or other
- Collaborators
- Schulthess Klinik, Buchinger Wilhelmi Development & Holding GmbH
- Responsible party
- Principal investigator, Dr. med. Nele Wagener, Charite University, Berlin, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07651462
- Sponsor's protocol ID
- EA1/279/24
- Acronym
- PreFAST-Hip
- Status last verified
- Jun 2026
- First submitted
- 11 Jun 2026
- Last updated
- 22 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: 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.
Publications
Cella D, Riley W, Stone A, Rothrock N, Reeve B, Yount S, Amtmann D, Bode R, Buysse D, Choi S, Cook K, Devellis R, DeWalt D, Fries JF, Gershon R, Hahn EA, Lai JS, Pilkonis P, Revicki D, Rose M, Weinfurt K, Hays R; PROMIS Cooperative Group. The Patient-Reported Outcomes Measurement Information System (PROMIS) developed and tested its first wave of adult self-reported health outcome item banks: 2005-2008. J Clin Epidemiol. 2010 Nov;63(11):1179-94. doi: 10.1016/j.jclinepi.2010.04.011. Epub 2010 Aug 4.
PubMed 20685078Nilsdotter AK, Lohmander LS, Klassbo M, Roos EM. Hip disability and osteoarthritis outcome score (HOOS)--validity and responsiveness in total hip replacement. BMC Musculoskelet Disord. 2003 May 30;4:10. doi: 10.1186/1471-2474-4-10. Epub 2003 May 30.
PubMed 12777182Delconte RB, Owyong M, Santosa EK, Srpan K, Sheppard S, McGuire TJ, Abbasi A, Diaz-Salazar C, Chun J, Rogatsky I, Hsu KC, Jordan S, Merad M, Sun JC. Fasting reshapes tissue-specific niches to improve NK cell-mediated anti-tumor immunity. Immunity. 2024 Aug 13;57(8):1923-1938.e7. doi: 10.1016/j.immuni.2024.05.021. Epub 2024 Jun 14.
PubMed 38878769Kong L, Cao J, Zhang Y, Ding W, Shen Y. Risk factors for periprosthetic joint infection following primary total hip or knee arthroplasty: a meta-analysis. Int Wound J. 2017 Jun;14(3):529-536. doi: 10.1111/iwj.12640. Epub 2016 Jul 10.
PubMed 27397553Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WP, Loria CM, Smith SC Jr; International Diabetes Federation Task Force on Epidemiology and Prevention; Hational Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; International Association for the Study of Obesity. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009 Oct 20;120(16):1640-5. doi: 10.1161/CIRCULATIONAHA.109.192644. Epub 2009 Oct 5.
PubMed 19805654Casals-Pascual C, Gonzalez A, Vazquez-Baeza Y, Song SJ, Jiang L, Knight R. Microbial Diversity in Clinical Microbiome Studies: Sample Size and Statistical Power Considerations. Gastroenterology. 2020 May;158(6):1524-1528. doi: 10.1053/j.gastro.2019.11.305. Epub 2020 Jan 10. No abstract available.
PubMed 31930986Valtetsiotis K, Di Martino A, Brunello M, Tassinari L, D'Agostino C, Traina F, Faldini C. The Potential Role of Gut Bacteriome Dysbiosis as a Leading Cause of Periprosthetic Infection: A Comprehensive Literature Review. Microorganisms. 2023 Jul 9;11(7):1778. doi: 10.3390/microorganisms11071778.
PubMed 37512950Salimi M, Karam JA, Willman M, Willman J, Lucke-Wold B, Khanzadeh S, Mirghaderi P, Parvizi J. Neutrophil to Lymphocyte Ratio and Periprosthetic Joint Infection: A Systematic Review and Meta-Analysis. J Arthroplasty. 2024 Mar;39(3):831-838. doi: 10.1016/j.arth.2023.08.067. Epub 2023 Aug 24.
PubMed 37633509Wilhelmi de Toledo F, Grundler F, Bergouignan A, Drinda S, Michalsen A. Safety, health improvement and well-being during a 4 to 21-day fasting period in an observational study including 1422 subjects. PLoS One. 2019 Jan 2;14(1):e0209353. doi: 10.1371/journal.pone.0209353. eCollection 2019.
PubMed 30601864Mesnage R, Grundler F, Schwiertz A, Le Maho Y, Wilhelmi de Toledo F. Changes in human gut microbiota composition are linked to the energy metabolic switch during 10 d of Buchinger fasting. J Nutr Sci. 2019 Nov 12;8:e36. doi: 10.1017/jns.2019.33. eCollection 2019.
PubMed 31798864McNally M, Sousa R, Wouthuyzen-Bakker M, Chen AF, Soriano A, Vogely HC, Clauss M, Higuera CA, Trebse R. The EBJIS definition of periprosthetic joint infection. Bone Joint J. 2021 Jan;103-B(1):18-25. doi: 10.1302/0301-620X.103B1.BJJ-2020-1381.R1.
PubMed 33380199
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07651462
- Acronym / sponsor ID
- PreFAST-Hip / EA1/279/24
- Conditions
- Hip Osteoarthritis, Arthroplasty, Replacement, Hip, Postoperative Complications, Surgical Wound Infection, Gastrointestinal Microbiome
- Keywords
- Therapeutic fasting, Buchinger fasting, Intermittent fasting, Gut microbiome, Immunophenotyping, Continuous glucose monitoring, Total hip arthroplasty, Metabolic syndrome
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 130 participants (estimated)
- Lead sponsor
- Charite University, Berlin, GermanyUniversity, hospital or other
- Collaborators
- Schulthess Klinik, Buchinger Wilhelmi Development & Holding GmbH
- Study start
- 1 Jul 2025 (actual)
- Primary completion
- 1 Sep 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 16 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Two-arm parallel-group design with 1:1 randomization stratified by metabolic status (metabolically healthy vs. metabolically unhealthy according to harmonized metabolic-syndrome criteria). Within each stratum, patients are randomized 1:1 to the structured 20-day preoperative fasting intervention versus standard preoperative care.
| Arm | Type | Receives |
|---|---|---|
| Preoperative Fasting (20 days; Buchinger Fastenbox + intermittent fasting) | Experimental | Other: Buchinger Fastenbox + intermittent fasting (20-day preoperative schedule)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. |
| Standard Preoperative Care | No intervention | –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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (8 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Other | Preoperative Fasting (20 days; Buchinger Fastenbox + intermittent fasting) |
Primary outcome
Change in plasma interleukin-8 (IL-8) concentration from baseline to Day +7 post-operatively
Time frame: 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
Time frame: Baseline (Day -21, before start of intervention) and Day +7 post-operatively
Shannon diversity index from shotgun-metagenomic stool sequencing
25 secondary outcomes
Perioperative kinetics of plasma cytokines (TNFα, IL-10, IL-6, IL-8)
Time frame: Baseline (Day -21), Day -1 pre-op, and 6 h, 24 h, 72 h, and Day +7 post-operatively
Serum C-reactive protein (CRP)
Time frame: Baseline (Day -21) and Day +7 post-operatively
T-cell subsets (CD3+, CD4+, CD8+) by flow cytometry
Time frame: Baseline (Day -21) and Day +7 post-operatively
B-cell frequency (CD19+)
Time frame: Baseline (Day -21) and Day +7 post-operatively
NK-cell frequency (CD16+/CD56+)
Time frame: Baseline (Day -21) and Day +7 post-operatively
T-cell activation / exhaustion markers (CD28, CD57, HLA-DR, PD-1)
Time frame: Baseline (Day -21) and Day +7 post-operatively
Monocyte HLA-DR expression (mHLA-DR)
Time frame: Baseline (Day -21) and Day +7 post-operatively
Neutrophil-to-lymphocyte ratio (NLR)
Time frame: Baseline (Day -21) and Day +7 post-operatively
Gut microbial beta-diversity
Time frame: Baseline (Day -21) and Day +7 post-operatively
Differential microbial abundance
Time frame: Baseline (Day -21) and Day +7 post-operatively
Microbial functional gene profile
Time frame: Baseline (Day -21) and Day +7 post-operatively
Continuous glucose monitoring (CGM) metrics
Time frame: Day -21 to day of surgery (continuous)
Daily self-monitored ketones (fasting arm)
Time frame: Day -20 to day of surgery
Daily body weight
Time frame: Day -20 to day of surgery, then Week 6, Month 3, Month 6 post-operatively
Daily waist circumference
Time frame: Day -20 to day of surgery
Daily blood pressure
Time frame: Day -20 to day of surgery
Hip disability and Osteoarthritis Outcome Score (HOOS)
Time frame: Baseline (Day -21), Week 6, Month 3, Month 6 post-operatively
Patient-Reported Outcomes Measurement Information System 33-item Profile (PROMIS-33)
Time frame: Baseline (Day -21), Week 6, Month 3, Month 6 post-operatively
Dietary intake (DEGS1 food frequency questionnaire)
Time frame: Baseline (Day -21)
Patient-reported postoperative infection symptoms (study-specific questionnaire)
Time frame: Weekly from Day +1 to Week 6 post-operatively
Postoperative infectious complications (EBJIS)
Time frame: Day 0 to Day 90 after surgery
Wound healing disorders
Time frame: Day 0 to Day 90 after surgery
Reoperation rate
Time frame: Day 0 to Day 90 after surgery
Length of hospital stay (LOS)
Time frame: From day of surgery to day of discharge (assessed up to 30 days)
Metabolic complications
Time frame: Day 0 to Day 30 after surgery
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2026.
- Background: PubMed 20685078Cella D, Riley W, Stone A, Rothrock N, Reeve B, Yount S, Amtmann D, Bode R, Buysse D, Choi S, Cook K, Devellis R, DeWalt D, Fries JF, Gershon R, Hahn EA, Lai JS, Pilkonis P, Revicki D, Rose M, Weinfurt K, Hays R; PROMIS Cooperative Group. The Patient-Reported Outcomes Measurement Information System (PROMIS) developed and tested its first wave of adult self-reported health outcome item banks: 2005-2008. J Clin Epidemiol. 2010 Nov;63(11):1179-94. doi: 10.1016/j.jclinepi.2010.04.011. Epub 2010 Aug 4.
- Background: PubMed 12777182Nilsdotter AK, Lohmander LS, Klassbo M, Roos EM. Hip disability and osteoarthritis outcome score (HOOS)--validity and responsiveness in total hip replacement. BMC Musculoskelet Disord. 2003 May 30;4:10. doi: 10.1186/1471-2474-4-10. Epub 2003 May 30.
- Background: PubMed 38878769Delconte RB, Owyong M, Santosa EK, Srpan K, Sheppard S, McGuire TJ, Abbasi A, Diaz-Salazar C, Chun J, Rogatsky I, Hsu KC, Jordan S, Merad M, Sun JC. Fasting reshapes tissue-specific niches to improve NK cell-mediated anti-tumor immunity. Immunity. 2024 Aug 13;57(8):1923-1938.e7. doi: 10.1016/j.immuni.2024.05.021. Epub 2024 Jun 14.
- Background: PubMed 27397553Kong L, Cao J, Zhang Y, Ding W, Shen Y. Risk factors for periprosthetic joint infection following primary total hip or knee arthroplasty: a meta-analysis. Int Wound J. 2017 Jun;14(3):529-536. doi: 10.1111/iwj.12640. Epub 2016 Jul 10.
- Background: PubMed 19805654Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WP, Loria CM, Smith SC Jr; International Diabetes Federation Task Force on Epidemiology and Prevention; Hational Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; International Association for the Study of Obesity. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009 Oct 20;120(16):1640-5. doi: 10.1161/CIRCULATIONAHA.109.192644. Epub 2009 Oct 5.
- Background: PubMed 31930986Casals-Pascual C, Gonzalez A, Vazquez-Baeza Y, Song SJ, Jiang L, Knight R. Microbial Diversity in Clinical Microbiome Studies: Sample Size and Statistical Power Considerations. Gastroenterology. 2020 May;158(6):1524-1528. doi: 10.1053/j.gastro.2019.11.305. Epub 2020 Jan 10. No abstract available.
- Background: PubMed 37512950Valtetsiotis K, Di Martino A, Brunello M, Tassinari L, D'Agostino C, Traina F, Faldini C. The Potential Role of Gut Bacteriome Dysbiosis as a Leading Cause of Periprosthetic Infection: A Comprehensive Literature Review. Microorganisms. 2023 Jul 9;11(7):1778. doi: 10.3390/microorganisms11071778.
- Background: PubMed 37633509Salimi M, Karam JA, Willman M, Willman J, Lucke-Wold B, Khanzadeh S, Mirghaderi P, Parvizi J. Neutrophil to Lymphocyte Ratio and Periprosthetic Joint Infection: A Systematic Review and Meta-Analysis. J Arthroplasty. 2024 Mar;39(3):831-838. doi: 10.1016/j.arth.2023.08.067. Epub 2023 Aug 24.
- Background: PubMed 30601864Wilhelmi de Toledo F, Grundler F, Bergouignan A, Drinda S, Michalsen A. Safety, health improvement and well-being during a 4 to 21-day fasting period in an observational study including 1422 subjects. PLoS One. 2019 Jan 2;14(1):e0209353. doi: 10.1371/journal.pone.0209353. eCollection 2019.
- Background: PubMed 31798864Mesnage R, Grundler F, Schwiertz A, Le Maho Y, Wilhelmi de Toledo F. Changes in human gut microbiota composition are linked to the energy metabolic switch during 10 d of Buchinger fasting. J Nutr Sci. 2019 Nov 12;8:e36. doi: 10.1017/jns.2019.33. eCollection 2019.
- Background: PubMed 33380199McNally M, Sousa R, Wouthuyzen-Bakker M, Chen AF, Soriano A, Vogely HC, Clauss M, Higuera CA, Trebse R. The EBJIS definition of periprosthetic joint infection. Bone Joint J. 2021 Jan;103-B(1):18-25. doi: 10.1302/0301-620X.103B1.BJJ-2020-1381.R1.
- Individual participant dataSharing planned: No. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Buchinger Fastenbox + intermittent fasting (20-day preoperative schedule) in people with Hip Osteoarthritis and Arthroplasty, Replacement, Hip, run by Charite University, Berlin, Germany at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Nele Wagener, Dr. med. (+49 30 450 615076, nele.wagener@charite.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in plasma interleukin-8 (IL-8) concentration from baseline to Day +7 post-operatively (time frame: Baseline (Day -21, before start of intervention) and Day +7 post-operatively). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07651462, which also lists 11 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2026.