Arginine and Nitric Oxide (NO) Early Prognostic Markers for Non-union Development

Arginine and Nitric Oxide (NO) Metabolism During Bone Healing and Non-union Development- Early Prognostic Markers

Objective: Primary objective is to study the arginine-NO metabolism during fracture healing and dysfunctional fracture healing. Secondary objective: to investigate if differences or decreased arginine and NO concentrations in bone healing form a prognostic marker for non-union development Hypothesis: Early detection of disturbances in the Arginine and nitric oxide metabolism during fracture healing are a good prognostic marker for non-union development.

Study design: Prospective observational study. Study population: All acute fracture patients (age >18 years), with a fracture of the tibia or femur attending the Department of General Surgery, to investigate the Arginine -NO metabolism during normal fracture healing and possible dysfunctional healing. In total 100 patients will be included during this study.

Main study parameters/endpoints:

Primary endpoints are arginine and Nitric Oxide levels in the plasma during normal and dysfunctional fracture healing the bone in patients with and without non-union Secondary endpoints are levels of Nitric Oxide citrulline, ornithine and other amino acids in bone and in plasma Other parameters: baseline demography details will be obtained, including possible confounders, such as bodyweight, smoking, alcohol abuse, which may interfere with the outcome of this study.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The extent of the burden and risk associated with participation is expected to be low during this study. In total, 7 blood samples will be taken during this study (45ml, in total). During the primary (and possible secondary) surgical procedure, bone debris will be taken. Bone debris is usually discarded but will be used for analysis in this study. There is no extra surgical procedure necessary to obtain the bone debris.

Study Overview

• Status: Unknown
• Conditions: Fracture Healing; Atrophic Non Union Development; Hypertrophic Non Union Development
• Intervention / Treatment: Other: no intervention

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Martijn Poeze, MD, PhD; Phone Number: 6262 +31433876543; Email: m.poeze@ah.unimaas.nl
• Study Contact Backup: Name: Nina Wijnands, MD, PhD-student; Phone Number: 9115 +31 43 3881497; Email: n.wijnands@ah.unimaas.nl

Study Locations

• Netherlands
  • Maastricht, Netherlands, 6229ER
    • Recruiting
    • Maastricht University Medical Center
    • Contact: Martijn Poeze, MD, PhD; Phone Number: 6262 +31433871956; Email: m.poeze@ah.unimaas.nl
    • Contact: Nina Wijnands, MD, PhD-student; Phone Number: 9115 +3143 3881497; Email: n.wijnands@ah.unimaas.nl
    • Principal Investigator: Martijn Poeze, MD,PhD
    • Sub-Investigator: nina Wijnands, MD, PhD-student

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with an acute fracture of the femur or tibia

Description

Inclusion Criteria:

• Written informed consent
• Age > 18 years
• Patient with a fracture of the femur or tibia for which a surgical procedure providing bone debris is performed as therapy

Exclusion Criteria:

• Patients with another bone fracture in their recent medical history
• Infectious complications, such as infected pseudo-arthrosis
• Use of chronic corticosteroids or nitrovasodilating medication
• Patients with severe metabolic disturbances (liver, and renal insufficiency, diabetes).
• Patients with metastases, haematological malignancies or chemotherapy

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
normal fracture healing; group in which normal fracture healing has occured	Other: no intervention; no intervention
atrophic; patients in which an atrophic non-union occured	Other: no intervention; no intervention
hypertrophic; patients in which a hypertrophic non-union occured	Other: no intervention; no intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The arginine, NO, citrulline and ornithine levels in plasma and bone debris during normal and dysfunctional fracture healing in patients with and without a non-union	1 year

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Investigators: Principal Investigator: Martijn Poeze, MD, PhD, Maastricht University Medical Center

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Anticipated): March 1, 2012

Study Registration Dates

• First Submitted: February 17, 2010
• First Submitted That Met QC Criteria: February 17, 2010
• First Posted (Estimate): February 18, 2010

Study Record Updates

• Last Update Posted (Estimate): April 7, 2010
• Last Update Submitted That Met QC Criteria: April 6, 2010
• Last Verified: April 1, 2010

More Information

Terms related to this study

• Keywords: fracture; arginine; NO; healing; non union
• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Hypertrophy
• Other Study ID Numbers: MEC-09-2-123