Clinical trial NCT03271580: Biofilm Modified Macrophage Phenotype and Function in Diabetic Wound Healing
Official title: Biofilm Modified Macrophage Phenotype and Function in Diabetic Wound Healing
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Wound
Bacterial Infections
Diabetes Mellitus
Infected Ulcer of Skin
Keywords: Wound healing
Diabetes
Inflammatory cells
Macrophage
Lead sponsor: Indiana University
Sponsor class: OTHER
First posted: 2017-09-05
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Twenty-eight diabetic subjects with chronic foot ulcer(s) that are receiving Negative Wound Pressure Therapy (NPWT) will be enrolled. Eighteen subjects will be infected and 10 subjects will be non-infected serving as the control for the study. The inclusion and exclusion criteria were carefully selected to enroll diabetic patients who have wound tissue oxygenation adequate to support wound healing.

Brief summary: The purpose of this study is to learn more about biofilm and to see how it affects diabetic wounds. A biofilm can occur if a chronic infection causes bacteria to grow in a slime enclosed group. This grouping of bacteria is called a biofilm.

Detailed description: There is one study visit with a 14-week follow-up that will take place during the participants standard of care visit at the Indiana University Health Comprehensive Wound Center (CWC). The following procedures will take place once your appointment has been completed:

* Informed consent will be signed (if not previously signed)
* A hemoglobin A1c drawn will be taken by research personnel, if one has not been done within the last 90 days to check your average blood sugar level.
* An Ankle Brachial Index (ABI) will be obtained if the participant has a leg wound. This is to ensure that participants have adequate blood flow to your wound. This is a non-invasive test which measures blood pressure in both of the participants arms and ankles.
* Demographics (such as your name and address and phone number, age), medical history, current medications, current standard of care labs, and wound data (measurements, cause of the wound, wound culture, assessments, treatments, and duration) will be recorded. The participant's medical record number will also be recorded.
* A photo of the wound site will be taken.
* Wound Vac Collection - The wound vac sponge will be collected (waste by product of the therapy) by the research staff.
* An optional two 3 mm punch tissue biopsies will be obtained from the participant's provider. To perform the biopsy, the area surrounding the wound will first be numbed using a local anesthetic agent that will be injected at the wound site. Then, a pencil-like instrument will be used to remove a small, thin cylinder of tissue. Each biopsy is about the size of this dot. After the tissue is removed, a sterile gauze will be placed on the area to stop any minor bleeding that may occur. The biopsies will be looked at in the laboratory to look at the microorganisms. You will not receive the results of the completed laboratory analysis. (Note: If two biopsies cannot be obtained per your physician's discretion, only one biopsy, debridement tissue (dead tissue that is removed from your wound) or no tissue will be obtained, and/or culture swabs (your wound will be swabbed with something like a Q-tip to collect cells to test for bacteria or other organisms in the wound) will be collected to test for infection.)

During the 14-week follow-up visit, research staff will review the participant's medical chart to determine the final status of the wound. If the participant does not return to the CWC at 14 weeks, the last CWC visit will be documented as the wound check follow-up. This does not require the participant to return for an extra study visit. This information will only be collected from their medical chart if available:

* Final status of the wound (healing, not healing, healed)
* Wound data (measurements), treatments, and any standard of care labs will be obtained
* A photo of your wound from the medical chart will be obtained (if available)

Eligibility criteria: Inclusion Criteria:

1. Age 18 and above years old
2. Willing and able to provide informed consent
3. Willing and able to comply with protocol instructions, including biopsies and study visits
4. Diabetics with an open wound
5. Receiving Negative Wound Pressure Therapy (NPWT)

Exclusion Criteria:

1. Inadequate arterial supply, as evidenced by any of the following (for wounds below the knee):

   1. TcOM \< 30mmHg
   2. ABI \< 0.7
   3. TBI \< 0.6
2. Women who are pregnant

Primary outcomes:
measure: Biofilm infection
timeFrame: 14 Weeks
measure: macrophage phenotyping
timeFrame: 14 Weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: IU Health Methodist Hospital
state: Indiana
city: Columbus
country: United States
facility: Davis Heart and Lung Institute
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Hospital East
state: Ohio
city: Columbus
country: United States
facility: Comprehensive Wound Care Centers, The Ohio State University Hospital
state: Ohio
city: Columbus
country: United States
facility: Martha Morehouse Medical Plaza
state: Ohio
Study officials:
affiliation: Indiana University
name: Sashwati Roy, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Breen JD, Karchmer AW. Staphylococcus aureus infections in diabetic patients. Infect Dis Clin North Am. 1995 Mar;9(1):11-24.
citation: Davis SC, Martinez L, Kirsner R. The diabetic foot: the importance of biofilms and wound bed preparation. Curr Diab Rep. 2006 Dec;6(6):439-45. doi: 10.1007/s11892-006-0076-x.
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.
citation: Hanke ML, Angle A, Kielian T. MyD88-dependent signaling influences fibrosis and alternative macrophage activation during Staphylococcus aureus biofilm infection. PLoS One. 2012;7(8):e42476. doi: 10.1371/journal.pone.0042476. Epub 2012 Aug 3.
citation: Hanke ML, Heim CE, Angle A, Sanderson SD, Kielian T. Targeting macrophage activation for the prevention and treatment of Staphylococcus aureus biofilm infections. J Immunol. 2013 Mar 1;190(5):2159-68. doi: 10.4049/jimmunol.1202348. Epub 2013 Jan 30.
citation: Neut D, Tijdens-Creusen EJ, Bulstra SK, van der Mei HC, Busscher HJ. Biofilms in chronic diabetic foot ulcers--a study of 2 cases. Acta Orthop. 2011 Jun;82(3):383-5. doi: 10.3109/17453674.2011.581265. Epub 2011 May 11. No abstract available.
citation: Zhao G, Usui ML, Lippman SI, James GA, Stewart PS, Fleckman P, Olerud JE. Biofilms and Inflammation in Chronic Wounds. Adv Wound Care (New Rochelle). 2013 Sep;2(7):389-399. doi: 10.1089/wound.2012.0381.