Effect of Tobacco Heating System (THS) on Closed Tibia Fracture Healing

Study Overview
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Brief Summary
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The goal of this clinical trial is to investigate the role of switching from cigarette smoking (CS) to tobacco heat system (THS) on the clinical outcome of closed tibia fractures from smokers' orthopedic patients. Validated and standardized assays, medical state and self-reported outcomes will be evaluated in orthopedic patients' smokers or switch from CS to using THS throughout six months compare to ex-smokers (control).

Official Title
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Evaluation of Tobacco Heating System (THS) Compared to Conventional Cigarette Smoking During the Closed Tibia Fracture Healing in Orthopedic Smokers' Patients

Conditions
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Smoking, Tibia Fracture

Intervention / Treatment
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* Device: Tobacco Heating System (THS)
* Other: Smoking abstinence


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Closed tibial fracture (according to AO/OTA classification: 41A2-41C3, 42A-C, 43A-C) which is surgically treated within 14 days after the trauma at the BG trauma clinic Tübingen. Additional inclusion criteria for the smoking and THS groups: Smokers with 10-20 packyears smoking history. Smoking history >10 years. Decision not to participate in the free smoking cessation seminars. Exclusion Criteria: Legal guardian or loss of capacity to consent. Refusal to participate in the study. Open tibial fractures or concomitant injuries or complications requiring surgery existing at the time of surgical indication. Initial surgical treatment of the tibial fracture has occurred ex domo. No initial surgical treatment within 14 days of sustained trauma. Using nicotine delivery electronic devices. Pre-existing autoimmune, immunological, bone or malignant diseases. Pregnant, breastfeeding and women of childbearing age with existing desire to have children. History of alcohol abuse or drug abuse. Taking antioxidants approval by the German Federal Institute for Drugs and Medical Devices (BfArM). Taking drugs with known effect on bone metabolism (according to Institute for medical and pharmaceutical examination issues (IMPP): allosteric CaSR modulators, bisphosphonates, calcium release inhibitors, alkaline earth ions, RANKL inhibitors, calcitriol, colecalciferol).

Ages Eligible for Study
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Minimum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Smokers<br>Participants subject to an orthopedic surgery (does not want to quit smoking conventional cigarettes) will continue smoking conventional cigarettes ad libitum for a period of 6 month post surgery | |
| Experimental: Smokers willing to switch to THS<br>Participants subject to an orthopedic surgery (currently smoking conventional cigarettes) will start to used THS ad libitum for a period of 6 month post surgery | Device: Tobacco Heating System (THS)<br>* Participant who are not willing to quit cigarette smoking during the study duration will switch from cigarettes to using THS<br>* Other names: IQOS 3 DUO;|
| Active Comparator: Ex Smokers<br>Participants subject to an orthopedic surgery will not smoke cigarettes or use electronic nicotine deliver systems for a period of 6 month post surgery | Other: Smoking abstinence<br>* Participant who are willing to quit cigarette smoking and will not use any electronic nicotine delivery system during the study duration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of Procollagen Type 1 N-Terminal Propeptide (CICP) | Marker collagen formation - bone formation | 6 months after tibia fracture surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of Alkaline Phosphatase (BAP) | Marker osteoblast activity | 6 months after tibia fracture surgery (time points: approx. one week pre-, six weeks post-, twelve weeks post- and six months post-surgery) | 
| Concentration of Osteoprogesterin | Decoy receptor RANKL - inhibit osteoclast differentiation | 6 months after tibia fracture surgery (time points: approx. one week pre-, six weeks post-, twelve weeks post- and six months post-surgery) | 
| Concentration of Osteopontin | Extracellular structural protein and an organic component of bone - favors osteoclast adherence | 6 months after tibia fracture surgery (time points: approx. one week pre-, six weeks post-, twelve weeks post- and six months post-surgery) | 
| Concentration of N-terminal telopeptide (NTx) | Marker collagen degradation - bone resorption | 6 months after tibia fracture surgery (time points: approx. one week pre-, six weeks post-, twelve weeks post- and six months post-surgery) | 
| Concentration of Interleukin 1 beta (IL-1β) |  | 6 months after tibia fracture surgery (time points: approx. one week pre-, six weeks post-, twelve weeks post- and six months post-surgery) | 
| Concentration of Interleukin 6 (IL-6) |  | 6 months after tibia fracture surgery (time points: approx. one week pre-, six weeks post-, twelve weeks post- and six months post-surgery) | 
| Concentration of Interferon gamma (IFN-γ) |  | 6 months after tibia fracture surgery (time points: approx. one week pre-, six weeks post-, twelve weeks post- and six months post-surgery) | 
| Concentration of Tumor Necrosis Factor Alpha (TNF-α) |  | 6 months after tibia fracture surgery (time points: approx. one week pre-, six weeks post-, twelve weeks post- and six months post-surgery) | 
| Number of bridged cortices in conventional X-ray |  | 6 months after tibia fracture surgery | 
| Number of bridged cortices in computed tomography scan |  | 6 months after tibia fracture surgery | 
| Bone Stiffness by a CT-based finite element method | Finite element method will be used to simulate the mechanical behavior (linear-elastic range) of the tibia and predict bending stiffness under a 3-point bending test | 6 months after tibia fracture surgery | 
| Functional index in trauma (FIX-IT) - Score | Assess weight-bearing and pain in patients with lower extremity fractures eight-bearing and pain in patients with lower extremity fractures. The score rank from 0 to 12 points in 2 domains: the ability to bear weight (maximum 6 points) and pain at the fracture site (maximum 6 points). The scores in both domains, which are weighted equally, are summed to obtain the final total score; (maximum 12 points indicates the highest level of function). | 6 months after tibia fracture surgery | 
| Loading of the injured extremity | The time period with no, sole contact, partial or full load on the injured extremity. | 6 months after tibia fracture surgery | 
| Lower Extremity Functional Scale (LEFS) - Score | The Lower Extremity Functional Scale (LEFS) is a questionnaire (20 questions) about a person's ability to perform everyday tasks. The LEFS will be used to evaluate the functional impairment of a patient with a disorder of lower extremity. The score rank from 0 to 80 points. The maximum score (80 point) indicates no functional limitations. | 6 months after tibia fracture surgery | 
| Number of complications associated with the healing process |  | 6 months after tibia fracture surgery | 
| Number of hospital stay and incapacity to work [days] |  | 6 months after tibia fracture surgery | 
| Physicians Global Assessment to measure quality of life (PROMIS GH10 v 1.2) - Score | The Global Health Patient-Reported Outcomes Measurement Information System (PROMIS- 10) scale is a ten-item patient reported measure of physical, mental and social health. Two summary scores are calculated from the results of the questions: a global physical health score and a global mental health score. These scores are then normalized to the general population using the T-score. The score ranges from 0 to 20 points. 0 points represent the most severe physical and/or mental impairment of the patient, while 20 points represent the best possible health status. | 6 months after tibia fracture surgery | 
| Visual Analog Score for pain (VAS) - Score | Visual Analog Scale for Pain (VAS) provide an estimate of patients' pain intensity. Scale from cero (no pain) to 10 (extreme pain). | 6 months after tibia fracture surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bone healing, Tobacco heating system, Smoking cessation