Clinical trial NCT02239419: Evaluation of Carbothera in the Treatment of Foot Ulcers
Official title: Evaluation of the Clinical Utility, Efficacy and Safety of a Novel Medical Device (Carbothera) in the Treatment of Foot Ulcers
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Critical Lower Limb Ischemia
Critical Limb Ischemia
Foot Ulcer
Skin Ulceration
Keywords: Critical Limb Ischemia
Limb Ischemia
Wound Care
Hemodialysis
Dialysis
Skin Ulceration
Lead sponsor: University of Manitoba
Sponsor class: OTHER
Collaborators: name: Mitsubishi-Rayon-Cleansui
First posted: 2014-09-12
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: Foot ulceration usually precedes more serious foot complications such as infection, gangrene or amputation. The risk of developing foot ulcers has been estimated to be higher in individuals with kidney disease. Patients with kidney disease receiving dialysis have an increased prevalence of critical limb ischemia. Carbon dioxide (CO2) foot bathing has been reported to improve subcutaneous microcirculation. The proposed clinical study will evaluate the therapeutic potential of CO2 enriched water (produced by the Carbothera device) on treating foot ulcers in patients with critical limb ischemia and undergoing hemodialysis. Forty individuals how have a distal extremity ulcer who are currently undergoing hemodialysis will participate in this study.

Detailed description: This is a multi-centered, placebo controlled and randomized clinical study designed to evaluate the therapeutic potential of CO2 enriched water on the treatment of distal extremity (foot) ulcers in patients with critical limb ischemia undergoing hemodialysis. Study participants will be patients receiving dialysis at two local hospitals in Winnipeg and will have been diagnosed with CLI and foot ulceration. Patients will be randomized to receive either treatment with CO2-enriched tap water, 1,000-1200 ppm CO2 (TREATMENT GROUP), or non-enriched tap water (CONTROL GROUP), bath therapy at 37ºC on the same day as dialysis (typically 3 times/wk), for 15 min for 4 months,. Blood (approximately 20 ml) will also be collected at baseline and at the end of every month of the treatment period (for a total of 5 collections) for the measurement of the different biomarkers.

Eligibility criteria: Inclusion Criteria:

1. Male and female participants ≥ 18 years of age with at least one distal extremity ulcer (arterial ischemic ulcer).
2. No acute medical illness and on conventional medical management prior to Carbothera.
3. Willingness and ability to provide written informed consent

Exclusion Criteria:

1. DVT or PE within 12 months.
2. Subjects with known active cancer, HIV, hepatitis B virus, hepatitis C virus, human transmissible spongiform encephalopathy, Treponema pallidum.
3. Subjects who are deemed to have an infection of the distal extremity ulcer.
4. Women who are pregnant
5. Unstable angina.
6. Acute MI within 1 month.
7. Stroke within 1 month.
8. Patient scheduled for revascularization during the 4-month intervention period.

Primary outcomes:
measure: Changes in Ulceration Area, Volume, Depth and Rate
timeFrame: 4 months
measure: Changes in Ankle Brachial Index (ABI)/Blood Flow
timeFrame: 4 Months
Secondary outcomes:
measure: Changes in Degree of Rest Pain
timeFrame: 4 Months
measure: Changes Limb Oxygenation
timeFrame: 4 Months
measure: Changes in Angiogenesis Marker: vascular endothelial growth factor (VEGF)
timeFrame: 4 Months
measure: Changes in Inflammatory Markers: TNFα, IL-6 and C - reactive protein
timeFrame: 4 Months
measure: Changes in Markers of Glucose Handling: HbA1c and Fasting Blood Glucose
timeFrame: 4 Months
measure: Changes in Lipid Profile
timeFrame: 4 Months
measure: Changes in Use of Bespoke Footwear and/or ability to Walk Barefoot
timeFrame: 4 Months
measure: Incidence of Amputation
timeFrame: 4 Months
measure: Use of Antibiotics Indicated for the Ulcer Treatment
timeFrame: 4 Months
Other outcomes:
Locations:
city: Winnipeg
country: Canada
facility: St. Boniface General Hospital
state: Manitoba
city: Winnipeg
country: Canada
facility: Health Sciences Centre- Rehabilitation Hospital
state: Manitoba
Study officials:
affiliation: St. Boniface Hospital
name: Amarjit S Arneja, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Alnaeb ME, Crabtree VP, Boutin A, Mikhailidis DP, Seifalian AM, Hamilton G. Prospective assessment of lower-extremity peripheral arterial disease in diabetic patients using a novel automated optical device. Angiology. 2007 Oct-Nov;58(5):579-85. doi: 10.1177/0003319707305685.
citation: Beckert S, Sundermann K, Wolf S, Konigsrainer A, Coerper S. Haemodialysis is associated with changes in cutaneous microcirculation in diabetes mellitus. Diabet Med. 2009 Jan;26(1):89-92. doi: 10.1111/j.1464-5491.2008.02610.x.
citation: Boulton AJ, Vileikyte L, Ragnarson-Tennvall G, Apelqvist J. The global burden of diabetic foot disease. Lancet. 2005 Nov 12;366(9498):1719-24. doi: 10.1016/S0140-6736(05)67698-2.
citation: Fellahi JL, Butin G, Zamparini G, Fischer MO, Gerard JL, Hanouz JL. Lower limb peripheral NIRS parameters during a vascular occlusion test: an experimental study in healthy volunteers. Ann Fr Anesth Reanim. 2014 Jan;33(1):e9-14. doi: 10.1016/j.annfar.2013.11.014. Epub 2013 Dec 27.
citation: Game FL, Chipchase SY, Hubbard R, Burden RP, Jeffcoate WJ. Temporal association between the incidence of foot ulceration and the start of dialysis in diabetes mellitus. Nephrol Dial Transplant. 2006 Nov;21(11):3207-10. doi: 10.1093/ndt/gfl427. Epub 2006 Jul 28.
citation: Hartmann BR, Bassenge E, Hartmann M. Effects of serial percutaneous application of carbon dioxide in intermittent claudication: results of a controlled trial. Angiology. 1997 Nov;48(11):957-63. doi: 10.1177/000331979704801104.
citation: Hayashi H, Yamada S, Kumada Y, Matsuo H, Toriyama T, Kawahara H. Immersing Feet in Carbon Dioxide-enriched Water Prevents Expansion and Formation of Ischemic Ulcers after Surgical Revascularization in Diabetic Patients with Critical Limb Ischemia. Ann Vasc Dis. 2008;1(2):111-7. doi: 10.3400/avd.AVDoa08001. Epub 2008 Oct 24.
citation: McGrath NM, Curran BA. Recent commencement of dialysis is a risk factor for lower-extremity amputation in a high-risk diabetic population. Diabetes Care. 2000 Mar;23(3):432-3. doi: 10.2337/diacare.23.3.432. No abstract available.
citation: Ndip A, Rutter MK, Vileikyte L, Vardhan A, Asari A, Jameel M, Tahir HA, Lavery LA, Boulton AJ. Dialysis treatment is an independent risk factor for foot ulceration in patients with diabetes and stage 4 or 5 chronic kidney disease. Diabetes Care. 2010 Aug;33(8):1811-6. doi: 10.2337/dc10-0255. Epub 2010 May 18.
citation: Nishimura N, Sugenoya J, Matsumoto T, Kato M, Sakakibara H, Nishiyama T, Inukai Y, Okagawa T, Ogata A. Effects of repeated carbon dioxide-rich water bathing on core temperature, cutaneous blood flow and thermal sensation. Eur J Appl Physiol. 2002 Aug;87(4-5):337-42. doi: 10.1007/s00421-002-0626-0. Epub 2002 Jun 7.
citation: Rogers LC, Bevilacqua NJ, Armstrong DG, Andros G. Digital planimetry results in more accurate wound measurements: a comparison to standard ruler measurements. J Diabetes Sci Technol. 2010 Jul 1;4(4):799-802. doi: 10.1177/193229681000400405.
citation: Shuler MS, Reisman WM, Whitesides TE Jr, Kinsey TL, Hammerberg EM, Davila MG, Moore TJ. Near-infrared spectroscopy in lower extremity trauma. J Bone Joint Surg Am. 2009 Jun;91(6):1360-8. doi: 10.2106/JBJS.H.00347.
citation: Toriyama T, Kumada Y, Matsubara T, Murata A, Ogino A, Hayashi H, Nakashima H, Takahashi H, Matsuo H, Kawahara H. Effect of artificial carbon dioxide foot bathing on critical limb ischemia (Fontaine IV) in peripheral arterial disease patients. Int Angiol. 2002 Dec;21(4):367-73.
citation: Wakimoto MM, Kadosaki M, Nagata H, Suzuki KS. The usefulness of near-infrared spectroscopy in the anesthetic management of endovascular aortic aneurysm repair. J Anesth. 2012 Dec;26(6):932-5. doi: 10.1007/s00540-012-1435-1. Epub 2012 Jun 26.
citation: Dachun Xu, Jue Li, Liling Zou, Yawei Xu, Dayi Hu, Pagoto SL, Yunsheng Ma. Sensitivity and specificity of the ankle--brachial index to diagnose peripheral artery disease: a structured review. Vasc Med. 2010 Oct;15(5):361-9. doi: 10.1177/1358863X10378376.
citation: Zhang Q, Lindberg LG, Kadefors R, Styf J. A non-invasive measure of changes in blood flow in the human anterior tibial muscle. Eur J Appl Physiol. 2001 May;84(5):448-52. doi: 10.1007/s004210100413.