Exploratory clinical trial to evaluate the efficacy and safety of carbon dioxide paste in healthy people

Abstract

Introduction: Scarring and pain are postoperative complications in patients after head and neck cancer treatment; however, there is no effective treatment. These complications are affected by local blood flow disorders, and it is well known that the transcutaneous application of carbon dioxide (CO2) improves local blood flow. Previously, we have shown that the transcutaneous application of carbon dioxide causes absorption of CO2 and increase the oxygen (O2) pressure in the treated tissue; it is expected that the application of CO2 may reduce scarring and pain caused by cancer treatment. We newly introduced the CO2 paste as a new CO2 application method, which does not need to use CO2 gas directly. In this study, we aimed to apply of CO2 paste to healthy people and to investigate its usefulness, safety and feasibility by analysing the increase in blood flow and frequency of adverse events. Methods: We applied carbon dioxide paste to skin over the sternocleidomastoid and gastrocnemius muscles of eight healthy volunteers. The changes in blood flow before and after the CO2 paste application using dynamic MRI, and changes in the vital signs were evaluated. Results: In the neck area and middle layer of the lower leg, the signal intensity (SI) significantly increased 60 seconds after application. In the surface layer of the lower leg, the SI was significantly increased 60 and 300 seconds after paste application. Although mild heat was noted after the paste application, no obvious adverse events occurred. Conclusion: We demonstrated the increase in SI by dynamic MRI at the site of the carbon dioxide paste application, which indicates the paste application is effective in improving the blood flow.

Transcutaneous carbon dioxide application suppresses the expression of cancer-associated fibroblasts markers in oral squamous cell carcinoma xenograft mouse model

“…In addition, patients with a vomiting reflex or limited mouth opening have difficulty receiving CO 2 . To overcome these problems, we have developed a CO 2 paste that does not produce gaseous CO 2 and is efficiently absorbed by the skin [46]. In the future, we hope to clarify the efficacy of this paste in inhibiting HNCs progression.…”

Transcutaneous carbon dioxide suppresses skeletal muscle atrophy in a mouse model of oral squamous cell carcinoma

“…Oe et al demonstrated similar changes to those that occur within muscles when aerobic exercise is performed [ 23 ]. And we have shown that the transcutaneous application of CO 2 to the human neck and lower extremities can improve blood flow [ 17 ]. However, the effect of transcutaneous application of CO 2 on cancer-related skeletal muscle atrophy is still unknown.…”

“…Carbon dioxide (CO 2 ) therapy is widely known as an effective treatment to improve blood flow and has been indicated for various diseases such as heart disease and skin conditions [ 16 ]. We demonstrated that transcutaneous application of CO 2 could improve local blood flow and promote the suppression of muscle atrophy and contraction, as well as the recovery of muscle damage [ 17 – 23 ]. However, while we have demonstrated the effect of transcutaneous application of CO 2 in suppressing tumor growth [ 24 ], we have not demonstrated the effect of cancer cachexia.…”

The Efficacy of Carbon Dioxide Paste in Alleviating Pain in Patients After Neck Dissection: Protocol for a Double-Blinded, Randomized Controlled Trial

“…In a phase 1 clinical study, we reported that CO 2 paste application increases blood flow to the skin and muscles without any side effects [ 26 ]. Since transcutaneous CO 2 application induces angiogenesis by inducing an artificial Bohr effect, we hypothesize that this simple and adaptable treatment can alleviate side effects and improve the QOL of patients undergoing neck dissection.…”

“…However, this method uses CO 2 gas, which is difficult to apply to the head and neck. In a recent study, we investigated the usefulness, safety, and feasibility of a CO 2 paste by analyzing the changes in blood flow in a phase 1 clinical study in healthy individuals [ 26 ]. The CO 2 paste reacted with water on the skin surface, could infiltrate CO 2 transcutaneously without the use of external CO 2 gas, and could be applied to the head and neck region.…”