Clinical trial NCT04561609: Transcutaneous Application of Gaseous CO2
Official title: The Effect of Transcutaneous Application of Gaseous CO2 on Diabetic Symmetrical Peripheral Neuropathy - A Double Blind Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Peripheral Diabetic Neuropathy
Keywords: peripheral diabetic neuropathy
transcutaneous CO2 application
Lead sponsor: University Medical Centre Ljubljana
Sponsor class: OTHER
First posted: 2020-09-23
Enrollment: 60
Sex: ALL
Minimum age (years): 30
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The use of transcutaneous application of gaseous CO2 for treatment of diabetic peripheral neuropathy. A double blind clinical trial. Control group receives placebo treatment.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Vibration sensation
timeFrame: before first therapy with CO2 or placebo and after 4 weeks of therapy with CO2 or placebo
measure: Change in Monofilament test
timeFrame: before first therapy with CO2 or placebo and after 4 weeks of therapy with CO2 or placebo
Secondary outcomes:
measure: Change in skin temperature
timeFrame: before first therapy with CO2 or placebo and after 4 weeks of therapy with CO2 or placebo
Other outcomes:
Locations:
city: Ljubljana
country: Slovenia
facility: UMCLjubljana
Study officials:
affiliation: UCMLjubljana
name: Igor Frangez, PhD, MD, DDS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Smith AG, Ramachandran P, Tripp S, Singleton JR. Epidermal nerve innervation in impaired glucose tolerance and diabetes-associated neuropathy. Neurology. 2001 Nov 13;57(9):1701-4. doi: 10.1212/wnl.57.9.1701.
citation: Sakai Y, Miwa M, Oe K, Ueha T, Koh A, Niikura T, Iwakura T, Lee SY, Tanaka M, Kurosaka M. A novel system for transcutaneous application of carbon dioxide causing an "artificial Bohr effect" in the human body. PLoS One. 2011;6(9):e24137. doi: 10.1371/journal.pone.0024137. Epub 2011 Sep 8.
citation: Macura M, Ban Frangez H, Cankar K, Finzgar M, Frangez I. The effect of transcutaneous application of gaseous CO2 on diabetic chronic wound healing-A double-blind randomized clinical trial. Int Wound J. 2020 Dec;17(6):1607-1614. doi: 10.1111/iwj.13436. Epub 2020 Jul 7.
citation: Tesfaye S, Boulton AJ, Dyck PJ, Freeman R, Horowitz M, Kempler P, Lauria G, Malik RA, Spallone V, Vinik A, Bernardi L, Valensi P; Toronto Diabetic Neuropathy Expert Group. Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes Care. 2010 Oct;33(10):2285-93. doi: 10.2337/dc10-1303.