Oral Supplementation With a Formulation Based on Cetylated Fatty Acids for Post-fracture Long Bone Healing (CETIULTRA-BONE)

Randomized, Double-blind, Placebo-controlled Study With 12 Weeks Oral Supplementation With a Formulation Based on Cetylated Fatty Acids to Support the Early Stage of Long Lower Limb Bone Healing After Fracture Stabilization

This clinical study aims to evaluate the potential benefits of a formulation based on Cetylated Fatty Acids in improving fracture healing of long bones in the lower limbs. The investigational product is administered orally over a 12-week period. Study procedures are limited to standard imaging techniques (radiography and echography), blood sampling, and completion of validated quality of life questionnaires.

Study Overview

• Status: Recruiting
• Conditions: Fracture Tibia; Fracture Femur
• Intervention / Treatment: Dietary supplement: CFA-based food supplement; Other: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Maria Sole Rossato; Phone Number: +390507846500; Email: ms.rossato@pharmanutra.it

Study Locations

• Belgium
  • Antwerp
    • Deurne, Antwerp, Belgium, 2100
      • Recruiting
      • AZ Monica
      • Contact: Wouter Peeters
      • Principal Investigator: Wouter Peeters
    • Herentals, Antwerp, Belgium, 2200
      • Recruiting
      • Algemeen Ziekenhuis Herentals
      • Contact: Willem-Jan Vleugels
      • Principal Investigator: Willem-Jan Vleugels
  • Brussels Capital
    • Brussels, Brussels Capital, Belgium, 1070
      • Recruiting
      • Hôpital Erasme - Cliniques universitaires de Bruxelles
      • Contact: Marc Jayankura
      • Principal Investigator: Marc Jayankura
    • Brussels, Brussels Capital, Belgium, 1090
      • Recruiting
      • Universitair Ziekenhuis Brussel
      • Contact: Maike Reul
      • Principal Investigator: Maike Reul
  • Flanders
    • Ghent, Flanders, Belgium, 9000
      • Recruiting
      • Universitair Ziekenhuis Gent
      • Contact: Jan Van Meirhaeghe
      • Principal Investigator: Jan Van Meirhaeghe
  • Limburg
    • Genk, Limburg, Belgium, 3600
      • Recruiting
      • Ziekenhuis Oost-Limburg
      • Contact: Ben Molenaers
      • Principal Investigator: Ben Molenaers

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Between 18 and 85 years old
• Presence of simple closed unifocal fracture (transverse, oblique, spiral, butterfly-shaped) in a long bone which need a standard of care surgical stabilization
• Presence of diaphyseal fracture of lower limb (femur or tibia, Subtrochanteric fracture are also allowed)
• Presence intramedullary nail
• Weight bearing as tolerated after surgery
• Having signed an informed consent, understand study procedures and ability to follow them
• Agreed to stop vitamin D intake for participants who take prophylactic Vitamin D

Exclusion Criteria:

• Treatment with vitamin D for medical purpose (Non-union, osteoporosis…)
• BMI > 30
• Open fracture
• Intra articular fracture
• Metaphyseal fracture
• Polytrauma patient (injury severity score: ISS >= 16)
• More than one lower limb long bone fracture
• Bridging plate
• Fracture treated conservatively with plaster
• Presence of active infection (body temperature ≥ 38°C or other symptoms)
• Any sign of severe vascular compromise across the fracture site (such as compartment syndrome, presence of serious vascular damage, etc.)
• Pathological fracture or diseases with a risk of recurrent falling (e.g. Parkinson's disease/syndrome, Hemiplegia after stroke, symptomatic stenosis of the spinal canal, polyneuropathy, epilepsy, recurring vertigo, recurring syncope)
• Participants with known bone disease which would negatively impact on the bone healing process
• Participants currently being treated with radiation, chemotherapy, immunosuppression, or steroid therapy
• Diabetic participants
• Daily smoker participants (cigarette or vaping containing nicotine)
• Participants under cortisone intake
• Participants under rheumatic medications intake
• Allergy or adverse effect of food supplement composition
• Unwilling or unable to take study medication
• Chronic drug or alcohol abuse
• Pregnant or breastfeeding at the time of enrolment
• Any other investigational treatment or food supplement within 3 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CFA-based supplement group; Participants will orally consume the assigned product for at least 12 weeks. Intake will be initiated from the day of Baseline (Visit 0) after all study procedures being performed until the morning of the last visit (Visit 3). Participants will take 2 sachets a day directly in their mouth.	Dietary supplement: CFA-based food supplement; oral gel containing cetilated fatty acids
Placebo Comparator: Placebo group; Participants will orally consume the assigned product for at least 12 weeks. Intake will be initiated from the day of Baseline (Visit 0) after all study procedures being performed until the morning of the last visit (Visit 3). Participants will take 2 sachets a day directly in their mouth.	Other: Placebo; oral gel coloured and flavoured as the IP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiographic Assessment of Callus Formation using the modified Radiographic Union Score for Tibia (mRUST).	Comparison between groups of radiographic assessment of the callus formation using mRUST 6 weeks after fracture stabilisation. The mRUST scale ranges from 4 to 16 points, where higher scores indicate better fracture healing (greater callus formation and union).	6 weeks after fracture stabilization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Assessment at Fracture Site using the Visual Analog Scale (VAS)	Change from baseline in pain perception in clinical assessment using the VAS 4 weeks after fracture stabilization. The VAS ranges from 0 to 10, where 0 indicates no pain and 10 indicates the worst imaginable pain. Higher scores represent worse outcomes (greater pain intensity).	4 weeks after fracture stabilization
Ultrasonographic Assessment of Callus Formation	Change from placebo group in ultrasonographic evaluation of hypervascularisation and callus formation. Measurement of callus size (length and thickness) in millimeters using B-mode ultrasound imaging at the fracture site. The assessment is performed 4 weeks after fracture stabilization. Larger callus size indicates better bone healing.	4 weeks after fracture stabilization
Radiographic Assessment of Callus Formation (modified Radiographic Union Score for Tibia - mRUST)	Radiographic union will be evaluated using the modified Radiographic Union Score for Tibia (mRUST), which rates healing on a 4-16 scale, with higher scores indicating better callus formation and more advanced fracture healing. Comparison between groups at Week 12.	12 weeks after fracture stabilization
Pain Assessment at Fracture Site (Visual Analog Scale - VAS)	Pain at the fracture site will be assessed using the Visual Analog Scale (VAS), a 0-100 mm scale, where higher scores indicate worse pain. The endpoint evaluates the change from baseline to Week 12.	12 weeks after fracture stabilization
Incidence of Complications	Comparison between groups of the number of complications observed at 4 and 12 weeks after fracture stabilization. Complications include superficial infection, deep infection, wound breakage, failure of fixation, bleeding, severe blood loss, nerve damage, swelling, deep vein thrombosis, and delayed healing.	4 weeks and 12 weeks after fracture stabilization
Minimal Clinically Important Improvement (MCII)	The MCII is calculated using the Visual Analog Scale (VAS) for pain, a 0-100 mm scale where higher scores indicate worse pain. MCII is defined as an absolute improvement of ≥15 mm or a relative improvement of ≥20% from baseline. The measure represents the proportion of participants achieving clinically meaningful pain improvement at each time point.	4 weeks and 12 weeks after fracture stabilization
Participant Acceptable Symptom State (PASS)	PASS is determined using the Visual Analog Scale (VAS) for pain, a 0-100 mm scale where higher scores indicate worse pain. PASS is defined as achieving a pain score <30 mm, corresponding to a symptom state considered acceptable by the participant. The measure represents the proportion of participants reaching this threshold.	4 weeks and 12 weeks after fracture stabilization
Participant Global Assessment (PGA)	PGA is assessed using a Visual Analog Scale (VAS), a 0-100 mm scale where higher scores indicate worse overall perception of recovery. Participants rate their overall status, taking into account pain, function, and wellbeing. Between-group comparison will be performed at each time point.	4 weeks and 12 weeks after fracture stabilization
Lower Extremity Functional Scale (LEFS)	Lower-limb functional recovery will be assessed using the Lower Extremity Functional Scale (LEFS), a validated 20-item questionnaire where each item is scored on a 0-4 scale. Total scores range from 0 to 80, with higher scores indicating better lower-extremity function. Between-group comparison will be performed at each visit.	4 weeks and 12 weeks after fracture stabilization
Quality of Life using the Short Form-36 (SF-36) questionnaire.	Health-related quality of life will be assessed using the Short Form-36 (SF-36) questionnaire. The SF-36 includes 8 domains, each scored from 0 to 100, where higher scores indicate better health status. Summary and domain-level results will be compared between groups at each time point.	4 weeks and 12 weeks after fracture stabilization
Painkiller and NSAID Consumption	Comparison between groups of the number of painkillers and NSAIDs consumed.	4 weeks and 12 weeks after fracture stabilization
Incidence of Adverse Events (AE) and Serious Adverse Events (SAE)	Comparison of the number of adverse events and serious adverse events reported.	4 weeks and 12 weeks after fracture stabilization
Participant Compliance Rate	Comparison between groups of participant compliance with study product intake	4 weeks and 12 weeks after fracture stabilization
Participant Satisfaction	Participant satisfaction with the study product will be assessed using a Likert scale, ranging from 1 to 5, where higher scores indicate greater satisfaction. The measure evaluates the participant's subjective perception of the product's acceptability and overall experience with the supplementation regimen. Comparison between groups will be performed at each study visit where data are collected.	4 weeks and 12 weeks after fracture stabilization

Collaborators and Investigators

• Sponsor: Pharmanutra S.p.a.
• Collaborators: Artialis
• Investigators: Principal Investigator: Jan Van Meirhaeghe, Department of Orthopaedics and Traumatology Ghent University Hospital (UZ Gent), Belgium

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2025
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: November 17, 2025
• First Submitted That Met QC Criteria: December 17, 2025
• First Posted (Actual): December 23, 2025

Study Record Updates

• Last Update Posted (Actual): December 23, 2025
• Last Update Submitted That Met QC Criteria: December 17, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries; Leg Injuries; Fractures, Bone; Femoral Fractures; Tibial Fractures
• Other Study ID Numbers: CETI ULTRA-BONE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No