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

Official title

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

Overview

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 lower limb (tibia and femur) 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).

Interventions

• 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 Smoking abstinence
  Participant who are willing to quit cigarette smoking and will not use any electronic nicotine delivery system during the study duration

Primary outcome measures

• Concentration of Procollagen Type 1 N-Terminal Propeptide (CICP) [Time frame: 6 months after tibia fracture surgery]

Secondary outcome measures (12)

• Concentration of Alkaline Phosphatase (BAP) [Time frame: 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 [Time frame: 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 [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: 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 [Time frame: 6 months after tibia fracture surgery]
• Number of bridged cortices in computed tomography scan [Time frame: 6 months after tibia fracture surgery]
• Bone Stiffness by a CT-based finite element method [Time frame: 6 months after tibia fracture surgery]
• Functional index in trauma (FIX-IT) - Score [Time frame: 6 months after tibia fracture surgery]

Eligibility criteria

Inclusion criteria

• Closed tibia or femur fracture (according to AO/OTA: 41A2-41C3, 42A-C, 43A-C, 32A-C, 33A2-3, 33B-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 fractures or concomitant injuries or complications requiring surgery existing at the time of surgical indication.
• Initial surgical treatment of the 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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Prevention

Study locations

Germany · 1 center

• Siegfried Weller Institutes, BG-Trauma Clinic, Department of Traumatology, Eberhard Karls — Tübingen

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. PMID 32952862
• 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. PMID 36708864
• Moritz Herbst, Romina Aspera-Werz, Benedikt Braun, Kevin Schulz, et al. (2024). Evaluation of the Tobacco Heating System (THS) During Closed Lower Limb Fracture Healing in Trauma Smokers' Patients. Qeios. doi:10.32388/DE0EAE.2.

Identifiers

NCT: NCT05859451 · IIS.SWI-THS.2022

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗