Wound Healing Endpoint and Recurrence

Diabetic Foot Ulcers Clinical Trial

Official title:

Wound Healing Endpoint and Recurrence

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT02577120
• Other study ID #: 1807366814
• Secondary ID: RFA-NR-15-0015R0
• Status: Suspended
• Phase: Phase 4
• Start date: January 8, 2019
• Est. completion date: February 2025

Study information

• Verified date: February 2024
• Source: Indiana University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This prospective pilot study is to enroll patients with clinically-defined infected wounds. Patients enrolled in the study will be followed for 16 weeks for wound closure (Phase A), and will then begin Phase B. 265 clinically diagnosed infected burn or chronic wound patients will be recruited for this study in Phase A. Based on the expectation that 89% of these wounds will heal within 16 weeks of enrollment, 234 of these patients will continue with the study for Phase B.

Description:

This prospective pilot study is to enroll patients with clinically-defined infected wounds. Patients enrolled in the study will be followed for 16 weeks for wound closure (Phase A), and will then begin Phase B. Wounds will be subjected to Standard of Care (SoC) followed by all Comprehensive Wound Center (CWC) wound physicians in the first 16 weeks. Trans - Epidermal Water Loss (TEWL) will be measured with a handheld, non-invasive device, the VapoMeter® Closed-Chambered device or using DermaLab TEWL probe. Both of these devices are used to read the device. They will be placed on the subjects skin and will read the TEWL measurement. When the device is placed on the skin, the measurement takes between 7-20 seconds with the standard adapter.

Study visit 1 will include informed consent being signed, baseline information collected, 2 biopsies will be collected unless the wound is not appropriate for biopsy or the patient chooses not to receive a biopsy then a swab for culture will be collected, wound image using a digital camera and Wound Vision Scout (a non-invasive, infrared imaging camera), and a quality of life survey will be completed by the subject. The patients medical chart will be followed for 16 weeks following visit 1. At 16 weeks (+/- 2 weeks) or within 10 days of wound closure whichever comes first, all subjects will return for study visit 2. If the target wound(s) is not yet healed at this visit, this visit will be part of their Standard of Care visit per the CWC. The patient's study participation will end at this visit but wound data will be collected, digital imaging of wound(s) and quality of life survey will be completed by the subject. If the target wound is determined by visual inspection to be healed at or prior to this visit, this will be a research only visit; the patient will continue to Phase B, a continuation of study visit 2. Various information will be collected on the data collection sheet, digital imaging and TEWL measurements will be recorded. The TEWL device will be placed on the skin. There will be 5 measurements obtained over the closed wound site. A reference (control) TEWL measurement will be taken from intact skin at an anatomically matched site on the patient.

A high TEWL/ defective closure is defined as a TEWL value that equals 2 times the value of the patient's control measurement. Patients who meet this criterion will be randomized to one of four groups: EpiCeram treatment, Ceramiseal treatment, Vaseline treatment or no treatment. Patients randomized to a treatment group will be supplied with study product and will be instructed to apply twice daily to the closed wound site for the remaining weeks of the study. All High TEWL patients will be asked to return for Study Visits 3-6. Distribution of study product as applicable. For this study, a low TEWL/ adequate closure is defined as a value less than 2 times the value of the patient's control measurement. Patients who meet this criterion will not be randomized into a treatment group, but will continue to receive standard of care per their physician and will be asked to return for study visits 3, 4, and

6. During these last visits the following activities will occur: TEWL measurements, digital imaging, sequential tape stripping to measure ceramide levels in the skin (up to 20 tape strips obtained). TEWL measurements will be obtained prior to tape stripping. The tape strips be completed after the TEWL measurements are obtained, wound site evaluation, various labs, medications review, distribution of study product (High TEWL only) and review of compliance and a quality of life survey is completed by the subject (visit 6 only).

There may be some discomfort with the tissue biopsy procedure depending on the amount of sensation the subject has at the site of the wound and will be numbed by applying local anesthesia as appropriate to area being biopsied. The amount of pain that occurs with wound biopsies will vary from person to person, but all efforts will be made to minimize pain and is within the boundaries of the existing wound to avoid giving the patient a separate new wound. Bleeding is a possible complication, but the risk is low for the small biopsies and is reduced by using local anesthetics with epinephrine, and silver nitrate sticks are available in each patient room to cauterize biopsy sites as needed. Infection is also a potential risk; however, wound tissue biopsies are routinely performed as the standard of care in the CWC to diagnose wound infection. The biopsy site will be appropriately monitored for infection by the physician managing the wound during routine wound clinic visits.

Possible risks for the use of the ceramide emulsion EpiCeram® are a temporary tingling sensation (10-15 minutes) and an extremely low risk of an allergic reaction. If this occurs the application of the cream will be stopped immediately. Possible risks for the use of Vaseline Petroleum and Ceramiseal™ are very low should be stopped if an allergic reaction occurs.There can be some minor redness and discomfort at the site of the tape stripping. The skin remains intact, i.e. the epidermis is not breached after the tape stripping procedure making this less than minimal risk. TEWL measurements are noninvasive and propose less than minimal risk.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 265
• Est. completion date: February 2025
• Est. primary completion date: February 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age = 18

• Willing to comply with protocol instructions, including all biopsies, study visits and study activities.

• One of the following:

1. Chronic wound of multiple etiologies and open for at least 30 days, including:

1. Diabetic foot ulcers, Wagner grade 1-3

2. Pressure ulcers, stage 2-3

3. Venous leg ulcers, confirmed by venous duplex

4. Burn wounds open

5. Other etiology, deemed appropriate for biopsy

2. Wounds not appropriate for biopsy due to either:

1. Almost healed at the time of enrollment (per physician)

2. Healed within 10 days prior to enrollment visit

3. Clinical contraindication to biopsy in the opinion of the wound care provider

• Adequate arterial blood flow as evidenced by at least one of the following (for subjects receiving tissue biopsy, if would is located on a lower extremity below the knee):

1. Transcutaneous oxygen measurement (TcOM) > 30 mmHg

2. Ankle-brachial index =0.7

3. Toe pressure > 30 mmHg

Exclusion Criteria:

• Individuals who are deemed unable to understand the procedures, risks and benefits of the study, (i.e. unable to provide informed consent)

• Diabetics with Hemoglobin A1c > 10%

• Subjects with marked immunodeficiency (HIV/AIDS, organ transplant patients and cancer patients and patients with autoimmune disease on immunosuppressive medications).

• Wounds closed or to be closed by flap or graft coverage - including stage 4 pressure ulcers and Wagner grade 4 or 5 diabetic foot ulcers

• Prisoners

• Patients with allergies to petrolatum

• Patients who are currently enrolled in another research study which includes investigational treatment and/or medication

Related Conditions & MeSH terms

• Burn Wound
• Chronic
• Chronic Wound
• Diabetic Foot
• Diabetic Foot Ulcers
• Foot Ulcer
• Leg Ulcer
• Pressure Ulcer
• Pressure Ulcers
• Recurrence
• Ulcer
• Varicose Ulcer
• Venous Leg Ulcers
• Wound
• Wounds and Injuries

Intervention

Device:
• Epiceram Skin Barrier Function
Epiceram is a non-sterile, viscous, lipid-rich emulsion

Biological:
• Vaseline Petroleum Jelly
A skin protectant used for temporarily protecting minor cuts, scraps, burns, and helps to protect and help relieve chapped or cracked skin and lips.
• Ceramiseal
Topical serum designed to fortify delicate skin with essential lipids. The proprietary blend of naturally occurring lipids contained in Ceramiseal are designed to improve the barrier function of your skin's outer layer; thereby restoring critical moisture balance and improving physical appearance and function.

Locations

Country	Name	City	State
United States	IU Health Methodist Hospital	Indianapolis	Indiana

Sponsors (2)

Lead Sponsor	Collaborator
Indiana University	National Institute of Nursing Research (NINR)

Country where clinical trial is conducted

United States, 

References & Publications (20)

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Barwell JR, Taylor M, Deacon J, Ghauri AS, Wakely C, Phillips LK, Whyman MR, Poskitt KR. Surgical correction of isolated superficial venous reflux reduces long-term recurrence rate in chronic venous leg ulcers. Eur J Vasc Endovasc Surg. 2000 Oct;20(4):363-8. doi: 10.1053/ejvs.2000.1196. — View Citation

Brooks B, Dean R, Patel S, Wu B, Molyneaux L, Yue DK. TBI or not TBI: that is the question. Is it better to measure toe pressure than ankle pressure in diabetic patients? Diabet Med. 2001 Jul;18(7):528-32. doi: 10.1046/j.1464-5491.2001.00493.x. — View Citation

Chamlin SL, Kao J, Frieden IJ, Sheu MY, Fowler AJ, Fluhr JW, Williams ML, Elias PM. Ceramide-dominant barrier repair lipids alleviate childhood atopic dermatitis: changes in barrier function provide a sensitive indicator of disease activity. J Am Acad Dermatol. 2002 Aug;47(2):198-208. doi: 10.1067/mjd.2002.124617. — View Citation

Disa JJ, Carlton JM, Goldberg NH. Efficacy of operative cure in pressure sore patients. Plast Reconstr Surg. 1992 Feb;89(2):272-8. doi: 10.1097/00006534-199202000-00012. — View Citation

FDA Wound Healing Clinical Focus Group.. Guidance for industry: chronic cutaneous ulcer and burn wounds-developing products for treatment. Wound Repair Regen. 2001 Jul-Aug;9(4):258-68. doi: 10.1046/j.1524-475x.2001.00258.x. No abstract available. — View Citation

Goodman CM, Cohen V, Armenta A, Thornby J, Netscher DT. Evaluation of results and treatment variables for pressure ulcers in 48 veteran spinal cord-injured patients. Ann Plast Surg. 1999 Jun;42(6):665-72. doi: 10.1097/00000637-199906000-00015. — View Citation

James GA, Swogger E, Wolcott R, Pulcini Ed, Secor P, Sestrich J, Costerton JW, Stewart PS. Biofilms in chronic wounds. Wound Repair Regen. 2008 Jan-Feb;16(1):37-44. doi: 10.1111/j.1524-475X.2007.00321.x. Epub 2007 Dec 13. — View Citation

Lavrijsen AP, Higounenc IM, Weerheim A, Oestmann E, Tuinenburg EE, Bodde HE, Ponec M. Validation of an in vivo extraction method for human stratum corneum ceramides. Arch Dermatol Res. 1994;286(8):495-503. doi: 10.1007/BF00371579. — View Citation

Lopez D, Vlamakis H, Kolter R. Generation of multiple cell types in Bacillus subtilis. FEMS Microbiol Rev. 2009 Jan;33(1):152-63. doi: 10.1111/j.1574-6976.2008.00148.x. Epub 2008 Nov 19. — View Citation

Park SC, Choi CY, Ha YI, Yang HE. Utility of Toe-brachial Index for Diagnosis of Peripheral Artery Disease. Arch Plast Surg. 2012 May;39(3):227-31. doi: 10.5999/aps.2012.39.3.227. Epub 2012 May 10. — View Citation

Pinnagoda J, Tupker RA, Agner T, Serup J. Guidelines for transepidermal water loss (TEWL) measurement. A report from the Standardization Group of the European Society of Contact Dermatitis. Contact Dermatitis. 1990 Mar;22(3):164-78. doi: 10.1111/j.1600-0536.1990.tb01553.x. — View Citation

Romanos MT, Raspovic A, Perrin BM. The reliability of toe systolic pressure and the toe brachial index in patients with diabetes. J Foot Ankle Res. 2010 Dec 22;3:31. doi: 10.1186/1757-1146-3-31. — View Citation

Roy S, Elgharably H, Sinha M, Ganesh K, Chaney S, Mann E, Miller C, Khanna S, Bergdall VK, Powell HM, Cook CH, Gordillo GM, Wozniak DJ, Sen CK. Mixed-species biofilm compromises wound healing by disrupting epidermal barrier function. J Pathol. 2014 Aug;233(4):331-343. doi: 10.1002/path.4360. Epub 2014 May 27. — View Citation

Roy S, Patel D, Khanna S, Gordillo GM, Biswas S, Friedman A, Sen CK. Transcriptome-wide analysis of blood vessels laser captured from human skin and chronic wound-edge tissue. Proc Natl Acad Sci U S A. 2007 Sep 4;104(36):14472-7. doi: 10.1073/pnas.0706793104. Epub 2007 Aug 29. — View Citation

Sen CK, Gordillo GM, Roy S, Kirsner R, Lambert L, Hunt TK, Gottrup F, Gurtner GC, Longaker MT. Human skin wounds: a major and snowballing threat to public health and the economy. Wound Repair Regen. 2009 Nov-Dec;17(6):763-71. doi: 10.1111/j.1524-475X.2009.00543.x. — View Citation

Smack DP, Harrington AC, Dunn C, Howard RS, Szkutnik AJ, Krivda SJ, Caldwell JB, James WD. Infection and allergy incidence in ambulatory surgery patients using white petrolatum vs bacitracin ointment. A randomized controlled trial. JAMA. 1996 Sep 25;276(12):972-7. — View Citation

Tetteh HA, Groth SS, Kast T, Whitson BA, Radosevich DM, Klopp AC, D'Cunha J, Maddaus MA, Andrade RS. Primary palmoplantar hyperhidrosis and thoracoscopic sympathectomy: a new objective assessment method. Ann Thorac Surg. 2009 Jan;87(1):267-74; discussion 274-5. doi: 10.1016/j.athoracsur.2008.10.028. — View Citation

Thiele JJ, Traber MG, Packer L. Depletion of human stratum corneum vitamin E: an early and sensitive in vivo marker of UV induced photo-oxidation. J Invest Dermatol. 1998 May;110(5):756-61. doi: 10.1046/j.1523-1747.1998.00169.x. — View Citation

Thiele JJ, Traber MG, Polefka TG, Cross CE, Packer L. Ozone-exposure depletes vitamin E and induces lipid peroxidation in murine stratum corneum. J Invest Dermatol. 1997 May;108(5):753-7. doi: 10.1111/1523-1747.ep12292144. — View Citation

* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Biofilm Infection effects to TEWL at wound sites	If a history of wound biofilm infection results in elevated TEWL at wound sites that appear closed, defectively closed wounds featuring high TEWL show higher "recurrence rate" than functionally closed wounds with low TEWL. This will be identified by how many subjects with a high TEWL reading and biofilm infection, have recurrence of their wound versus subjects with a low TEWL reading.	12 weeks
Primary	Ceramiseal and EpiCeram restore barrier function to wounds in patients	If topical application of the Ceramiseal™ or the FDA approved EpiCeram® restores barrier function to defectively closed wounds. These will be compared to a Placebo cream, Vaseline and will be seen after 3 months of application to the wound site.	12 weeks