Intermittent Fasting Versus Carbohydrate Drinks Before Surgery (PRINCESS)

Preoperative Intermittent Fasting Versus Carbohydrate Loading to Reduce Insulin Resistance: a Randomised Controlled Trial

The purpose of this study is to investigate whether time-restricted feeding, a form of intermittent fasting, before surgery improves insulin resistance around the time of surgery, compared to carbohydrate drinks and standard fasting before surgery.

Study Overview

• Status: Recruiting
• Conditions: Insulin Resistance; Perioperative Care; Orthopedic Surgery; Intermittent Fasting; Carbohydrate Loading; Preoperative Fasting
• Intervention / Treatment: Behavioral: Time-restricted feeding; Dietary supplement: Carbohydrate loading

Detailed Description

Patients in the Time-Restricted Feeding (TRF) group will follow a daily TRF regimen consisting of an 8h ad libitum eating period and a 16h water fasting period during the last two weeks before surgery, followed by routine preoperative fasting before surgery.

Patients in the CarboHydrate Loading (CHL) group will follow their usual diet in the pre-surgical weeks and will receive a maltodextrin beverage on the evening before surgery, as well as two hours before induction of anaesthesia.

• Study Type: Interventional
• Enrollment (Estimated): 75
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Benedikt Preckel, MSc; Phone Number: +31205669111; Email: b.preckel@amsterdamumc.nl
• Study Contact Backup: Name: A. Stobbe, MSc; Phone Number: +31205669111; Email: a.y.stobbe@amsterdamumc.nl

Study Locations

• Netherlands
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1105AZ
      • Recruiting
      • Amsterdam UMC location AMC
      • Contact: R. van Wilpe, MSc; Phone Number: +31205669111; Email: r.vanwilpe@amsterdamumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Undergoing elective orthopaedic surgery;
• Intermediate, major or complex surgery according to the Surgical Outcome Risk Tool (SORT; http://www.sortsurgery.com/) severity of surgery classification;
• Scheduled for surgery at least 17 days from the date of screening;
• Motivated to follow a time restricted feeding regimen.
• Willing and able to provide written informed consent.

Exclusion Criteria:

• History of diabetes mellitus;
• History of feeding or eating disorders;
• History of delayed gastric emptying or gastro-oesophageal reflux
• Active malignancy
• Patients classified as ASA IV by the attending anaesthetist;
• BMI < 18.5 or ≥ 35;
• Outpatient or day case surgery;
• Palliative surgery;
• Participation in another clinical trial that is interfering with the procedures or outcomes of the PRINCESS trial;
• Patients unable to fully comply to study needs (e.g. legally incapable patients or patients unable to communicate in Dutch).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Time-restricted feeding; Subjects will follow a daily time-restricted feeding regimen consisting of an 8h ad libitum eating period and a 16h water fasting period during the last two weeks before surgery, followed by routine preoperative fasting before surgery.	Behavioral: Time-restricted feeding; Subjects in the will be instructed to follow a TRF regimen consisting of a daily 8h ad libitum eating period and 16h water fasting period during the last 2 weeks before surgery. Participants will be encouraged to begin their eating period at 08:00h and end it at 16:00h, since the metabolic benefits of TRF appear to be considerably more pronounced when the eating period starts early in the day.
Active Comparator: Carbohydrate loading; Subjects will follow their usual diet in the pre-surgical weeks and will receive a maltodextrin beverage on the evening before surgery, as well as two hours before induction of anaesthesia	Dietary supplement: Carbohydrate loading; Subjects will continue their usual diet and will receive two quantities of a clear beverage containing 12.5 g/100 mL maltodextrin (50 kCal/100 mL, pH 5.0); 800 mL at 22.00h on the evening before surgery and 400 mL two hours before anaesthesia induction.
No Intervention: Control group; Subjects will continue their usual diet and proceed with standard preoperative fasting (i.e., eat up until 6 hours and take clear liquids up until 2 hours before induction of anaesthesia).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin resistance on postoperative day 1	Insulin resistance according to the updated homeostasis model assessment of insulin resistance (HOMA2-IR)	Postoperative day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in HOMA2-IR	This is a calculated value between two timepoints, in contrary to the primary outcome that solely measures postoperative insulin resistance. The preoperative HOMA2-IR and the postoperative HOMA2-IR are used to determine whether there has been a change (increase or decrease) of the insulin resistance.	From baseline to day of surgery, from baseline to postoperative day 1 and from day of surgery to postoperative day 1.
Beta-cell function	The beta-cell function is based on the updated HOMA2 model. In addition to glucose and insulin, C-peptide measurements will be done to calculate HOMA2-B.	The day of surgery and the first postoperative day
Patient wellbeing	Patient wellbeing during and after the intervention and on the first postoperative day is measured by combining the five-level EuroQol five-dimensional questionnaire (EQ-5D-5L) utility score (change in scores 1-5 over 5 domains, 1 is best and 5 is worst), and the Quality of Recovery-15 (QoR-15) score (0-150, 0 is the worst and 150 is the best recovery).	During the two weeks preoperatively, until one day postoperatively

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Collaborators: European Society of Anaesthesiology and Intensive Care
• Investigators: Principal Investigator: Jeroen Hermanides, MSc, Amsterdam UMC, location AMC

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2023
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: February 27, 2023
• First Submitted That Met QC Criteria: February 27, 2023
• First Posted (Actual): March 8, 2023

Study Record Updates

• Last Update Posted (Actual): October 22, 2024
• Last Update Submitted That Met QC Criteria: October 18, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Perioperative Care; Insulin Resistance; Orthopedic Surgery; HOMA-IR; Carbohydrate Loading; Time Restricted Feeding
• Additional Relevant MeSH Terms: Metabolic Diseases; Glucose Metabolism Disorders; Hyperinsulinism; Insulin Resistance
• Other Study ID Numbers: PRINCESS trial

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be made available upon reasonable request following the completion of the trial and publication of the final manuscript. The shared data may include de-identified data that contains individual-level data collected during the trial. Researchers seeking data access must submit a research proposal and analysis plan outlining objectives, methodology, and relevance. If applicable, approval by a medical ethics research committee is required. Proposals will be reviewed to ensure that the request aligns with scientific and ethical standards, and data access will be granted under a data use/sharing agreement that stipulates the terms and conditions for data usage.
• IPD Sharing Time Frame: After completion of the trial and publication of the final manuscript.
• IPD Sharing Access Criteria: Researchers seeking data access must submit a research proposal and analysis plan outlining objectives, methodology, and relevance. If applicable, approval by a medical ethics research committee is required. Proposals will be reviewed to ensure that the request aligns with scientific and ethical standards, and data access will be granted under a data use/sharing agreement that stipulates the terms and conditions for data usage.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No