Plain English Summary
Background and study aims
Diabetic foot ulcers (DFU) occur as a result of various factors which occur with higher frequency and intensity in the diabetic population. This causes a broken area in the foot that is unable to heal due to uncontrolled blood sugar levels. DFU lesions are responsible for more hospitalisations than any other complication of diabetes. Diabetes is the leading cause of non-traumatic lower extremity amputations in the United States, with approximately 5% of diabetics developing foot ulcers each year and 1% requiring amputation. The management of diabetic foot ulcers requires offloading the wound by using appropriate therapeutic footwear, daily saline (cleaning) or similar dressings to provide a moist wound environment, debridement (removal) when necessary, antibiotic therapy, and controlling blood sugar.
Approximately 70% of DFUs are shown to heal with good standard of care, however, at least 30% become chronic wounds. These non-healing wounds are at greater risk for infection and lower extremity amputation. Consequently, more therapy is considered for patients with chronic DFUs to improve patient outcomes, lower treatment costs and reduce the risk of complications. There has been an increase in clinical trials evaluating the use of skin and tissue substitutes, including bioengineered skin, autografts (skin or tissue taken from the individual and put in another place), allografts (skin or tissue taken from another person) and xenografts on DFUs. These clinical studies have demonstrated improved healing rates and are fewer amputations of limbs. Additionally, retrospective studies and case reports have found that the application of microvascular (a minimally manipulated microvascular human tissue product) flaps and free tissue transfer to chronic and diabetic wounds result in enhanced patient outcomes. The aim of this study is to evaluate the effects of human mirovascular tissue in treating DFU.
Who can participate?
Adults aged 18 and older with chronic DFU.
What does the study involve?
Participants are randomly allocated to one of two groups. Those in the first group receive the standard level of care. Those in the second group receive the standard level of care as well as microvascular tissue on their wound. Participants are treated for 12 weeks. Participants undergo imaging and biopsies (samples taken) at baseline, six and 12 weeks to assess their healing.
What are the possible benefits and risks of participating?
Participants may benefit from having their chronic DFU healed. There are no direct risks with participation.
Where is the study run from?
This study is being run by Microvascular Tissues, Inc. (USA) and takes place in Foot and Ankle Associates of Southwest Virginia (USA).
When is the study starting and how long is it expected to run for?
April 2017 to February 2019
Who is funding the study?
Microvascular Tissues, Inc. (USA)
Who is the main contact?
Mrs Lael Pickett
lpickett@mvtissues.com
Trial website
Contact information
Type
Public
Primary contact
Mrs Lael Pickett
ORCID ID
Contact details
Microvascular Tissues
Inc.
6199 Cornerstone Court
Suite 109
San Diego
92121
United States of America
+1 858 522 0633
lpickett@mvtissues.com
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
VMV-DFU-01, Version 1.1
Study information
Scientific title
A multi-center randomised controlled clinical trial evaluation the effect of allogenic microvascular tissue in the treatment of wagner one and two diabetic foot ulcers
Acronym
Study hypothesis
The primary study hypothesis is that the proportion of wounds healed at 12 weeks, after up to 12 weeks of mVASC and SOC or SOC alone, will be equal for Groups 1 and 2. Formally, H0: I1–I2 = 0; HA: I1–I2 = D1≠0, where I1 is the proportion of wounds healed in Group 1, I2 is same metric for Group 2, D1 is the difference (I1–I2); assuming the alternative hypothesis and statistical test used is chi square/Fisher exact test.
Ethics approval
Western IRB (WIRB), 08/31/2017, ref: 20171089
Study design
Interventional randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
GP practices
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Wagner 1 and 2 diabetic foot ulcers (DFUs)
Intervention
Randomisation is performed using envelopes that have be prepared prior to the randomisation visits.
Group 1: Standard of Care (SOC)
Group 2: SOC + mVASC. mVASC is a minimally manipulated microvascular human tissue product.
Study subjects are treated weekly for up to 12 weeks. Subjects receiving mVASC receive a quantity of mVASC appropriate to the size of their ulcer.
A subject of subjects undergo LUNA imaging and biopsy at selected time points (baseline, six and 12 weeks). All subjects undergo wound imaging.
Intervention type
Other
Phase
Drug names
Primary outcome measure
Percentage of index ulcers healed is measured using photographs of the index ulcer at baseline and 12 weeks.
Secondary outcome measures
1. Percentage of index ulcers is measured using photographs at baseline and at 6 weeks
2. Time to heal is measured using photographs at 6 and 12 weeks
3. Percent Area Reduction (PAR) measured using photographs at 6 and 12 weeks
4. Changes in peripheral neuropathy appendage area is measured using a probe and photographs at baseline and at 12 weeks
5. Changes in wound quality of life (per W-QoL) is measured using the validated W-QofL instrument at baseline and at 12 weeks
6. Change in pain levels during trial is measured using a visual analog scale (VAS) at baseline and at 12 weeks
7. Difference in cellulitis and/or infection is measured using a visual scoring system at baseline and at 12 weeks
Overall trial start date
17/04/2017
Overall trial end date
31/03/2019
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. At least 18 years old
2. Presence of a DFU, Wagner 1 or 2 grade, extending at least through the dermis or subcutaneous tissue and may involve the tendon, muscle, or bone, on any aspect of the foot, provided it is below the medial aspect of the malleolus
3. The index ulcer will be the largest ulcer if two or more DFUs are present with the same Wagner grade and will be the only one evaluated in the study. If other ulcerations are present on the same foot they must be more than 2 cm distant from the index ulcer
4. Index ulcer (i.e. current episode of ulceration) has been present for greater than four weeks prior to the initial screening visit and less than 1-year, as of the date subject consents for study
5. Index ulcer is a minimum of 0.75 cm2 and a maximum of 25 cm2 at first screening visit (SV1) and first treatment visit (TV1)
6. Adequate circulation to the affected foot as documented by a dorsal transcutaneous oxygen measurement (TCOM) or a skin perfusion pressure (SPP) measurement of ≥ 30 mmHg, or an Ankle Branchial Index (ABI) between 0.7 and 1.3 within 3 months of SV1, using the affected study extremity. As an alternative arterial Doppler ultrasound can be performed evaluating for biphasic dorsalis pedis and posterior tibial vessels at the level of the ankle or a Toe Brachial Index (TBI) of > 0.6 is acceptable
7. The index ulcer has been offloaded for at least 14 days prior to randomization
8. Females of childbearing potential must be willing to use acceptable methods of contraception (birth control pills, barriers or abstinence) during the course of the study and undergo pregnancy tests
9. Subject understands and is willing to participate in the clinical study and can comply with weekly visits
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
100
Participant exclusion criteria
1. Index ulcer(s) deemed by the investigator to be caused by a medical condition other than diabetes
2. Index ulcer, in the opinion of the investigator, is suspicious for cancer and should undergo an ulcer biopsy to rule out a carcinoma of the ulcer
3. Subjects with a history of more than 2 weeks treatment with immune-suppressants (including systemic corticosteroids >10mg daily dose), cytotoxic chemotherapy or application of topical steroids to the ulcer surface within one month prior to SV1, or who receive such medications during the screening period, or who are anticipated to require such medications during the course of the study
4. Subjects taking a selective COX-2 inhibitor (e.g., celexocib) for any condition
5. Subjects on any investigational drug(s) or therapeutic device(s) within 30 days preceding SV1
6. History of radiation at the ulcer site (regardless of time since last radiation treatment)
7. Index ulcer has been previously treated or will need to be treated with any prohibited therapies. (See Section 7.3 of this protocol for a list of prohibited medications and therapies)
8. Presence of any condition(s) which seriously compromises the subject’s ability to complete this study or has a known history of poor adherence with medical treatment
9. Osteomyelitis or bone infection of the affected foot near the site of the wound as verified by X-ray within 30 days prior to randomization. (In the event of an ambiguous diagnosis, the Principal Investigator will make the final decision)
10. Subject is pregnant or breast-feeding
11. Presence of diabetes with poor metabolic control as documented with an HbA1c > 12.0 within 90 days of randomization
12. Subjects with end stage renal disease as evidenced by a serum creatinine ≥ 3.0 mg/dL within 120 days of randomization
13. Index ulcer has reduced in area by 20% or more after 14 days of SOC from SV1 to the TV1/randomization visit
Recruitment start date
11/09/2017
Recruitment end date
31/03/2019
Locations
Countries of recruitment
United States of America
Trial participating centre
Foot and Ankle Associates of Southwest Virginia
1 Dudley Street
VA
Martinsville
24112
United States of America
Trial participating centre
Foot and Ankle Associates of Southwest Virginia
222 Walnut Avenue
VA
Roanoke
24016
United States of America
Sponsor information
Organisation
Microvascular Tissues, Inc.
Sponsor details
6199 Cornerstone Court
Suite 109
San Deigo
92121
United States of America
+1 858 522 0633
lpickett@mvtissues.com
Sponsor type
Industry
Website
Funders
Funder type
Industry
Funder name
Microvascular Tissues, Inc.
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Planned publication in a high-impact peer review journal.
IPD sharing statement:
The participant level data will be stored in the study database. Since this is a large study (approximately 100 subjects), the participant level data will be provided as demographic information and sub-analyses provided. Individual clinical sites may choose to publish participant level for their sites.
Intention to publish date
31/03/2020
Participant level data
Stored in repository
Basic results (scientific)
Publication list