Transcutaneous Application of Gaseous CO2

Not Applicable

• Conditions: Peripheral Diabetic Neuropathy
• Interventions: Other: Transcutaneous CO2 application; Other: Placebo treatment

• Registration Number: NCT04561609
• Lead Sponsor: University Medical Centre Ljubljana

Brief Summary

The research is designed to evaluate influence of transcutaneous application of CO2 (carbon dioxide) on peripheral diabetic neuropathy. Transcutaneous application of CO2 is known to have immediate effect on vasodilatation and elevates oxygen release from Hb via the Bohr effect. After repetition of the therapies neoangiogenesis is induced. Impairment of microcirculation is one of the causes of diabetic peripheral neuropathy and improvement in circulation could have positive effect also on peripheral neuropathy. In order to evaluate the effect of transcutaneous application of CO2 on peripheral neuropathy in diabetic patients the investigators designed a randomised double blind clinical trial.

Detailed Description

Transcutaneous application of gaseous CO2 showed to be a successful adjuvant therapy in treatment of chronic wounds in diabetic patients (PMID: 32633896). During that research patients reported improvement in peripheral sensation after treatment. Therefore, in order to investigate the influence of transcutaneous application of gaseous CO2 in peripheral diabetic neuropathy the investigators designed a randomised double blind research. 60 diabetic patients with peripheral diabetic neuropathy will be randomised in study and control group. Study group will receive 20 treatments with CO2 (each workday for 4 weeks). Lower part of the body is inserted into therapeutic wrap that is filled with 99.9% CO2 gas for 45 minutes. The same approach will be used in control group but in their case the therapeutic wrap will be filled with air. In both groups investigator will evaluate vibration sensation, monofilament test and temperature of the big toe before first and after 4 weeks of treatment. Patients as well as investigator (doctor) will be blind for the group belonging of the patients. The medical nurse performing all the therapies will randomise the patients using random number generator into study and control group. The nurse will be the only one knowing group belonging of the patients until the obtained results from both groups will be compared.

Study Timeline

• Study Start: 2020-05-02
• Study First Submitted: 2020-09-06
• Study First Submitted QC: 2020-09-17
• Study First Posted: 2020-09-23
• Status Verified: 2020-11
• Last Update Submitted: 2020-11-02
• Last Update Posted: 2020-11-03
• Primary Completion: 2021-09-30
• Study Completion: 2021-12-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

• patients with diabetes and peripheral symmetrical diabetic neuropathy
• with unilateral chronic wound, without previous amputations
• with scores above 3 on the Michigan Neuropathy Scoring Instrument

Exclusion Criteria

• diabetic patients with asymmetrical peripheral neuropathy
• patients with severe comorbidities: deep vein thrombosis, chronic kidney diseases grade III and IV, chronic heart diseases NYHA (New York Heart Association) III and IV, patients with known malignant diseases, patients with progressive infection, signs of systemic infection with elevated inflammatory markers or osteomyelitis

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CO2 treated	Transcutaneous CO2 application	Patients receiving treatment with transcutaneous application of gaseous CO2 on lower limbs
control	Placebo treatment	Patients receiving placebo treatment with air on lower limbs

Primary Outcome Measures

Name	Time	Method
Change in Monofilament test	before first therapy with CO2 or placebo and after 4 weeks of therapy with CO2 or placebo	Monofilament testing is performed using Semmes Weinstein Monofilament (SWM) 10 g on 8 standard points on each foot (on the plantar surface of the great toe, third and fifth toe, on the plantar surface of the first, third and fifth metatarsal head, on the plantar arch and on the plantar surface of the calcaneus). Results are presented as number of points (out of 16) with no sensation.
Change in Vibration sensation	before first therapy with CO2 or placebo and after 4 weeks of therapy with CO2 or placebo	Vibration sensation is performed using a 128 Hz tuning fork on 5 standard points on each foot (on the skin above a bony prominence the first metatarsophalangeal joint (MPT), the apex of the hallux, malleolus, diaphysis of tibia and tibia tuberosity). Results are presented as number of points (out of 10) with no vibration sensation.

Secondary Outcome Measures

Name	Time	Method
Change in skin temperature	before first therapy with CO2 or placebo and after 4 weeks of therapy with CO2 or placebo	the temperature measured with infrared thermometer on the plantar of the big toes using infrared thermometer. Temperature measurement was standardized - before treatment (in order to exclude increased temperature during the CO2 therapy due to vasodilatation). Patients are left to lie on the examination table, barefoot for 20 minutes to adjust to the room temperature.

Trial Locations

Locations (1)

UMCLjubljana; 🇸🇮 Ljubljana, Slovenia