Evaluation of Carbothera in the Treatment of Foot Ulcers

NCT02239419 | Unknown

• 1 other identifier: B2014:037
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

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.

Conditions

Critical Lower Limb Ischemia; Critical Limb Ischemia; Foot Ulcer; Skin Ulceration

Keywords

Critical Limb Ischemia; Limb Ischemia; Wound Care; Hemodialysis; Dialysis; Skin Ulceration

Outcome Measures

Primary Outcomes (2)

• Changes in Ulceration Area, Volume, Depth and Rate

  Measurement of ulceration area, volume, depth and rate will be completed at Baseline (Day 1), Week 4, Week 8, Week 12 and Week 16 using an approved (Health Canada) portable hand-held 3D digital wound imaging camera (SilhouetteStar from Aranz Medical, New Zealand).

  4 months

• Changes in Ankle Brachial Index (ABI)/Blood Flow

  A continuous wave, hand held Doppler machine will be used with a blood pressure cuff and a conventional sphygmomanometer to measure the systolic pressure in both the posterior tibial (PT) and dorsalis pedis (DP) arteries. If no PT or DP arterial signals are found, the anterior tibial and/or peroneal artery pressure will be recorded. The ankle systolic pressure and brachial systolic blood pressure will be calculated as ankle systolic pressure/bronchial systolic pressure (ABI). The subject will be asked to rest supine for 10 minutes before ABI measurements. Brachial systolic and diastolic pressures as well as heart rate will be measured. Measurement of ABI will be conducted at Baseline (Day 1), and at weeks 4, 8, 12 and 16.

  4 Months

Secondary Outcomes (9)

• Changes in Degree of Rest Pain

  4 Months

• Changes Limb Oxygenation

  4 Months

• Changes in Angiogenesis Marker: vascular endothelial growth factor (VEGF)

  4 Months

• Changes in Inflammatory Markers: TNFα, IL-6 and C - reactive protein

  4 Months

• Changes in Markers of Glucose Handling: HbA1c and Fasting Blood Glucose

  4 Months

Study Arms (2)

CO2-Enriched Tap Water (Carbothera)

EXPERIMENTAL

CO2-enriched tap water (CO2 concentration, 1000-1200 ppm) maintained at a temperature of 37˚C. Tap water will be enriched with CO2 by the investigational Carbothera device.

Procedure: CO2-Enriched Tap Water (Carbothera)

Non-CO2-Enriched Tap Water

PLACEBO COMPARATOR

Non-CO2-enriched tap water (i.e. normal tap water) maintained at a temperature of 37˚C.

Procedure: Non-CO2-Enriched Tap Water

Interventions

CO2-Enriched Tap Water (Carbothera) PROCEDURE

Participants will undergo foot bathing with CO2-enriched tap water (CO2 concentration, 1000-1200 ppm) maintained at a temperature of 37˚C with an immersion time of 15 mins, 3 times per week for 4 consecutive months. Participants will be rested on a chair for 15 min before foot bathing. If participant is undergoing hemodialysis, foot bathing will occur prior to their routine hemodialysis procedure.

CO2-Enriched Tap Water (Carbothera)

Non-CO2-Enriched Tap Water PROCEDURE

Participants will undergo foot bathing with non-CO2-enriched tap water maintained at a temperature of 37˚C with an immersion time of 15 mins, 3 times per week for 4 consecutive months. Participants will be rested on a chair for 15 min before foot bathing. If participant is undergoing hemodialysis, foot bathing will occur prior to their routine hemodialysis procedure.

Non-CO2-Enriched Tap Water

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• University of Manitoba: lead
• Mitsubishi-Rayon-Cleansui: collaborator

Study Sites (2)

St. Boniface General Hospital

Winnipeg, Manitoba, R2H 2A6, Canada

RECRUITING

Health Sciences Centre- Rehabilitation Hospital

Winnipeg, Manitoba, R3A 1A4, Canada

RECRUITING

Related Publications (16)

• 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.

  PMID: 18024941 BACKGROUND

• 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.

  PMID: 19125767 BACKGROUND

• 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.

  PMID: 16291066 BACKGROUND

• 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.

  PMID: 24373673 BACKGROUND

• 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.

  PMID: 16877485 BACKGROUND

• 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.

  PMID: 9373047 BACKGROUND

• 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.

  PMID: 23555347 BACKGROUND

• 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.

  PMID: 10868890 BACKGROUND

• 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.

  PMID: 20484126 BACKGROUND

• 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.

  PMID: 12172871 BACKGROUND

• 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.

  PMID: 20663440 BACKGROUND

• 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.

  PMID: 19487513 BACKGROUND

• 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.

  PMID: 12518118 BACKGROUND

• 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.

  PMID: 22733429 BACKGROUND

• 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.

  PMID: 20926495 BACKGROUND

• 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.

  PMID: 11417434 BACKGROUND

Related Links

• St. Boniface Hospital Research Centre
• St. Boniface Hospital

MeSH Terms

Conditions

Chronic Limb-Threatening Ischemia; Foot Ulcer; Skin Ulcer

Condition Hierarchy (Ancestors)

Peripheral Arterial Disease; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Ischemia; Foot Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Leg Ulcer

Study Officials

• Amarjit S Arneja, MD

  St. Boniface Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Paramjit Tappia, PhD

CONTACT

204-258-1230; ptappia@sbrc.ca

Amarjit S Arneja, MD

CONTACT

204-787-2270; aarneja@exchange.hsc.mb.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2014
• First Posted: September 12, 2014
• Study Start: September 1, 2014
• Primary Completion: April 1, 2016
• Study Completion: December 1, 2016
• Last Updated: October 30, 2015

Record last verified: 2014-09

Locations

CA (2)