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

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

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).

Study Overview

• Status: Recruiting
• Conditions: Smoking; Tibia Fracture
• Intervention / Treatment: Device: Tobacco Heating System (THS); Other: Smoking abstinence

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Andreas K. Nüssler, Prof. Dr.; Phone Number: +49070716061065; Email: andreas.nuessler@med.uni-tuebingen.de
• Study Contact Backup: Name: Benedikt J. Braun, PD. Dr.; Phone Number: +49070716063017; Email: bbraun@bgu-tuebingen.de

Study Locations

• Germany
  • Baden-Württemberg
    • Tübingen, Baden-Württemberg, Germany, 72076
      • Recruiting
      • Siegfried Weller Institutes, BG-Trauma Clinic, Department of Traumatology, Eberhard Karls University Tübingen
      • Contact: Andreas K. Nüssler, Prof. Dr.; Phone Number: +49070716061065; Email: andreas.nuessler@med.uni-tuebingen.de
      • Contact: Benedik J. Braun, PD. Dr. med.; Phone Number: +49070716063017; Email: bbraun@bgu-tuebingen.de
      • Principal Investigator: Andreas K. Nüssler, Prof. Dr.
      • Sub-Investigator: Benedik J. Braun, PD. Dr. med.
      • Sub-Investigator: Romina H. Aspera-Werz, Dr. sc. hum.

Participation Criteria

Eligibility Criteria

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

Description

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).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Smokers; 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; 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); Participant who are not willing to quit cigarette smoking during the study duration will switch from cigarettes to using THS; Other Names: IQOS 3 DUO
Active Comparator: Ex Smokers; 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; Participant who are willing to quit cigarette smoking and will not use any electronic nicotine delivery system during the study duration

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of Soluble intercellular adhesion molecule-1 (sICAM-1)		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 High densitiy lipoprotein cholesterol levels (HDL)		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 Leucocytes		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 Erythrocytes		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 Hemoglobin		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 Thrombocytes		6 months after tibia fracture surgery (time points: approx. one week pre-, six weeks post-, twelve weeks post- and six months post-surgery)
Mean corpuscular volume		6 months after tibia fracture surgery (time points: approx. one week pre-, six weeks post-, twelve weeks post- and six months post-surgery)
Hematocrit levels		6 months after tibia fracture surgery (time points: approx. one week pre-, six weeks post-, twelve weeks post- and six months post-surgery)
Mean corpuscular hemoglobin levels		6 months after tibia fracture surgery (time points: approx. one week pre-, six weeks post-, twelve weeks post- and six months post-surgery)
Corpuscular hemoglobin concentration		6 months after tibia fracture surgery (time points: approx. one week pre-, six weeks post-, twelve weeks post- and six months post-surgery)
Protein c reactive levels		6 months after tibia fracture surgery (time points: approx. one week pre-, six weeks post-, twelve weeks post- and six months post-surgery)
Alcohol consume	Compensation cigarette abstinence with alcohol	6 months after tibia surgery
Questionnaire on Smoking Urges (QSU-G) - Score		6 months after tibia surgery
Smoking behaviour	Number of cigarettes or THS heets consume	6 months after tibia surgery
Nicotine withdrawal syndrome assessment - Checklist		6 months after tibia surgery

Collaborators and Investigators

• Sponsor: University Hospital Tuebingen
• Collaborators: Philip Morris Products S.A.

Publications and helpful links

General Publications

• Aspera-Werz RH, Ehnert S, Muller M, Zhu S, Chen T, Weng W, Jacoby J, Nussler AK. Assessment of tobacco heating system 2.4 on osteogenic differentiation of mesenchymal stem cells and primary human osteoblasts compared to conventional cigarettes. World J Stem Cells. 2020 Aug 26;12(8):841-856. doi: 10.4252/wjsc.v12.i8.841.
• Weng W, Bovard D, Zanetti F, Ehnert S, Braun B, Uynuk-Ool T, Histing T, Hoeng J, Nussler AK, Aspera-Werz RH. Tobacco heating system has less impact on bone metabolism than cigarette smoke. Food Chem Toxicol. 2023 Mar;173:113637. doi: 10.1016/j.fct.2023.113637. Epub 2023 Jan 25.

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2023
• Primary Completion (Estimated): October 15, 2025
• Study Completion (Estimated): April 17, 2026

Study Registration Dates

• First Submitted: March 30, 2023
• First Submitted That Met QC Criteria: May 4, 2023
• First Posted (Actual): May 16, 2023

Study Record Updates

• Last Update Posted (Actual): November 29, 2023
• Last Update Submitted That Met QC Criteria: November 28, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Smoking cessation; Tobacco heating system; Bone healing
• Additional Relevant MeSH Terms: Wounds and Injuries; Leg Injuries; Fractures, Bone; Tibial Fractures
• Other Study ID Numbers: IIS.SWI-THS.2022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All IPD (in an anonymous form) that underlie results in a publication
• IPD Sharing Time Frame: 6 months after results are published in peer-reviewed international journal
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

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