Preoperative Fasting and the Gut Microbiome Before Hip Replacement

NCT07651462 | Recruiting

• 1 other identifier: EA1/279/24
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 1

Brief 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. 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.

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; Preoperative optimization

Outcome Measures

Primary Outcomes (2)

• 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

  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

  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)

  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

Study Arms (2)

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.

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.

Interventions

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.

Preoperative Fasting (20 days; Buchinger Fastenbox + intermittent fasting)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead
• Buchinger Wilhelmi Clinic: collaborator
• Schulthess Klinik: collaborator

Study Sites (1)

Centrum für Muskuloskeletale Chirurgie (CMSC), Charité - Universitätsmedizin Berlin

Berlin, State of Berlin, 10117, Germany

RECRUITING

Related Publications (11)

• 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.

  PMID: 20685078 BACKGROUND

• Nilsdotter 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.

  PMID: 12777182 BACKGROUND

• Delconte 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.

  PMID: 38878769 BACKGROUND

• Kong 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.

  PMID: 27397553 BACKGROUND

• Alberti 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.

  PMID: 19805654 BACKGROUND

• Casals-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.

  PMID: 31930986 BACKGROUND

• Valtetsiotis 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.

  PMID: 37512950 BACKGROUND

• Salimi 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.

  PMID: 37633509 BACKGROUND

• Wilhelmi 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.

  PMID: 30601864 BACKGROUND

• Mesnage 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.

  PMID: 31798864 BACKGROUND

• McNally 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.

  PMID: 33380199 BACKGROUND

MeSH Terms

Conditions

Osteoarthritis, Hip; Postoperative Complications; Surgical Wound Infection; Intermittent Fasting; Metabolic Syndrome

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Wound Infection; Infections; Fasting; Feeding Behavior; Behavior; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Central Study Contacts

Nele Wagener, Dr. med.

CONTACT

+49 30 450 615076; nele.wagener@charite.de

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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.

Study Record Dates

• First Submitted: June 11, 2026
• First Posted: June 16, 2026
• Study Start: July 1, 2025
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: June 22, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)