Back to resultsEvaluation of Carbothera in the Treatment of Foot Ulcers
Primary Purpose
Critical Lower Limb Ischemia, Critical Limb Ischemia, Foot Ulcer
Status
Unknown status
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
CO2-Enriched Tap Water (Carbothera)
Non-CO2-Enriched Tap Water
Sponsored by
About this trial
This is an interventional prevention trial for Critical Lower Limb Ischemia focused on measuring Critical Limb Ischemia, Limb Ischemia, Wound Care, Hemodialysis, Dialysis, Skin Ulceration
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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.
Sites / Locations
- St. Boniface General HospitalRecruiting
- Health Sciences Centre- Rehabilitation HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
CO2-Enriched Tap Water (Carbothera)
Non-CO2-Enriched Tap Water
Arm Description
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.
Non-CO2-enriched tap water (i.e. normal tap water) maintained at a temperature of 37˚C.
Outcomes
Primary Outcome Measures
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).
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.
Secondary Outcome Measures
Changes in Degree of Rest Pain
Changes in the degree of rest pain will be measured using the McGill Pain Questionnaire which will be administered at Baseline (Day 1), Weeks 8 and 16.
Changes Limb Oxygenation
Changes in limb blood volume and oxygenation will be recorded using noninvasive near infra-red spectroscopy (NIRS). NIRS measures the percentage of hemoglobin oxygen saturation in the microcirculation of tissue up to 3 cm below the skin.
Changes in Angiogenesis Marker: vascular endothelial growth factor (VEGF)
A fasting blood sample will be obtained from the participant at the Baseline Visit (Day 1), and Weeks 4, 8, 12 and 16 visits for the purpose of measurement of the angiogenesis marker: vascular endothelial growth factor (VEGF).
Changes in Inflammatory Markers: TNFα, IL-6 and C - reactive protein
A fasting blood sample will be obtained from the participant at the Baseline Visit (Day 1), and Weeks 4, 8, 12 and 16 visits for the purpose of measurement of inflammatory markers: TNFα, IL-6 and C - reactive protein.
Changes in Markers of Glucose Handling: HbA1c and Fasting Blood Glucose
A fasting blood sample will be obtained from the participant at the Baseline Visit (Day 1), and Weeks 4, 8, 12 and 16 visits for the purpose of measurement of blood glucose and glycated hemoglobin (hemoglobin A1c).
Changes in Lipid Profile
A fasting blood sample will be obtained from the participant at the Baseline Visit (Day 1), and Weeks 4, 8, 12 and 16 visits for the purpose of measurement of the participant's lipid profile, specifically, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides.
Changes in Use of Bespoke Footwear and/or ability to Walk Barefoot
A patient self-report on the use of bespoke footwear or insoles and the ability to walk barefoot at home will be obtained at the Baseline Visit (Day 1) and at Weeks 8 and 16.
Incidence of Amputation
Incidence of amputation of the distal extremity under study will be monitored during participation in the study.
Use of Antibiotics Indicated for the Ulcer Treatment
Use of antibiotics indicated for the ulcer treatment during the period of the trial will also be recorded in a questionnaire.
Full Information
NCT ID
NCT02239419
First Posted
September 10, 2014
Last Updated
October 29, 2015
Sponsor
University of Manitoba
Collaborators
Mitsubishi-Rayon-Cleansui
1. Study Identification
Unique Protocol Identification Number
NCT02239419
Brief Title
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
2. Study Status
Record Verification Date
September 2014
Overall Recruitment Status
Unknown status
Study Start Date
September 2014 (undefined)
Primary Completion Date
April 2016 (Anticipated)
Study Completion Date
December 2016 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Manitoba
Collaborators
Mitsubishi-Rayon-Cleansui
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Critical Lower Limb Ischemia, Critical Limb Ischemia, Foot Ulcer, Skin Ulceration
Keywords
Critical Limb Ischemia, Limb Ischemia, Wound Care, Hemodialysis, Dialysis, Skin Ulceration
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
CO2-Enriched Tap Water (Carbothera)
Arm Type
Experimental
Arm Description
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.
Arm Title
Non-CO2-Enriched Tap Water
Arm Type
Placebo Comparator
Arm Description
Non-CO2-enriched tap water (i.e. normal tap water) maintained at a temperature of 37˚C.
Intervention Type
Procedure
Intervention Name(s)
CO2-Enriched Tap Water (Carbothera)
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
Non-CO2-Enriched Tap Water
Intervention Description
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.
Primary Outcome Measure Information:
Title
Changes in Ulceration Area, Volume, Depth and Rate
Description
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).
Time Frame
4 months
Title
Changes in Ankle Brachial Index (ABI)/Blood Flow
Description
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.
Time Frame
4 Months
Secondary Outcome Measure Information:
Title
Changes in Degree of Rest Pain
Description
Changes in the degree of rest pain will be measured using the McGill Pain Questionnaire which will be administered at Baseline (Day 1), Weeks 8 and 16.
Time Frame
4 Months
Title
Changes Limb Oxygenation
Description
Changes in limb blood volume and oxygenation will be recorded using noninvasive near infra-red spectroscopy (NIRS). NIRS measures the percentage of hemoglobin oxygen saturation in the microcirculation of tissue up to 3 cm below the skin.
Time Frame
4 Months
Title
Changes in Angiogenesis Marker: vascular endothelial growth factor (VEGF)
Description
A fasting blood sample will be obtained from the participant at the Baseline Visit (Day 1), and Weeks 4, 8, 12 and 16 visits for the purpose of measurement of the angiogenesis marker: vascular endothelial growth factor (VEGF).
Time Frame
4 Months
Title
Changes in Inflammatory Markers: TNFα, IL-6 and C - reactive protein
Description
A fasting blood sample will be obtained from the participant at the Baseline Visit (Day 1), and Weeks 4, 8, 12 and 16 visits for the purpose of measurement of inflammatory markers: TNFα, IL-6 and C - reactive protein.
Time Frame
4 Months
Title
Changes in Markers of Glucose Handling: HbA1c and Fasting Blood Glucose
Description
A fasting blood sample will be obtained from the participant at the Baseline Visit (Day 1), and Weeks 4, 8, 12 and 16 visits for the purpose of measurement of blood glucose and glycated hemoglobin (hemoglobin A1c).
Time Frame
4 Months
Title
Changes in Lipid Profile
Description
A fasting blood sample will be obtained from the participant at the Baseline Visit (Day 1), and Weeks 4, 8, 12 and 16 visits for the purpose of measurement of the participant's lipid profile, specifically, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides.
Time Frame
4 Months
Title
Changes in Use of Bespoke Footwear and/or ability to Walk Barefoot
Description
A patient self-report on the use of bespoke footwear or insoles and the ability to walk barefoot at home will be obtained at the Baseline Visit (Day 1) and at Weeks 8 and 16.
Time Frame
4 Months
Title
Incidence of Amputation
Description
Incidence of amputation of the distal extremity under study will be monitored during participation in the study.
Time Frame
4 Months
Title
Use of Antibiotics Indicated for the Ulcer Treatment
Description
Use of antibiotics indicated for the ulcer treatment during the period of the trial will also be recorded in a questionnaire.
Time Frame
4 Months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Paramjit Tappia, PhD
Phone
204-258-1230
Email
ptappia@sbrc.ca
First Name & Middle Initial & Last Name or Official Title & Degree
Amarjit S Arneja, MD
Phone
204-787-2270
Email
aarneja@exchange.hsc.mb.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Amarjit S Arneja, MD
Organizational Affiliation
St. Boniface Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
St. Boniface General Hospital
City
Winnipeg
State/Province
Manitoba
ZIP/Postal Code
R2H 2A6
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Paramjit Tappia, PhD
Phone
204-258-1230
Email
ptappia@sbrc.ca
First Name & Middle Initial & Last Name & Degree
Bram Ramjiawan, PhD
Phone
204-235-3372
Email
bramjiawan@sbgh.mb.ca
First Name & Middle Initial & Last Name & Degree
Chris Sathianathan, MD
First Name & Middle Initial & Last Name & Degree
Mauro Verrelli, MD
Facility Name
Health Sciences Centre- Rehabilitation Hospital
City
Winnipeg
State/Province
Manitoba
ZIP/Postal Code
R3A 1A4
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amarjit S Arneja, MD
Phone
204-787-2270
First Name & Middle Initial & Last Name & Degree
Amarjit S Arneja, MD
12. IPD Sharing Statement
Citations:
PubMed Identifier
18024941
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.
Results Reference
background
PubMed Identifier
19125767
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.
Results Reference
background
PubMed Identifier
16291066
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.
Results Reference
background
PubMed Identifier
24373673
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.
Results Reference
background
PubMed Identifier
16877485
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.
Results Reference
background
PubMed Identifier
9373047
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.
Results Reference
background
PubMed Identifier
23555347
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.
Results Reference
background
PubMed Identifier
10868890
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.
Results Reference
background
PubMed Identifier
20484126
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.
Results Reference
background
PubMed Identifier
12172871
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.
Results Reference
background
PubMed Identifier
20663440
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.
Results Reference
background
PubMed Identifier
19487513
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.
Results Reference
background
PubMed Identifier
12518118
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.
Results Reference
background
PubMed Identifier
22733429
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.
Results Reference
background
PubMed Identifier
20926495
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.
Results Reference
background
PubMed Identifier
11417434
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.
Results Reference
background
Links:
URL
http://www.sbrc.ca
Description
St. Boniface Hospital Research Centre
URL
http://www.sbgh.mb.ca
Description
St. Boniface Hospital
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Evaluation of Carbothera in the Treatment of Foot Ulcers
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