Determination of the Pathophysicologic Collagen Changes in the Diabetic Achilles Tendon
This is a pilot study examining tendon collagen, collagen cross-linking, and markers of tendon extracellular matrix metabolism in the Achilles tendon of diabetic patients with ulcerations and amputations of the lower extremity.
Diabetic Foot Ulcers
|Study Design:||Observational Model: Case Control
Time Perspective: Prospective
|Official Title:||Determination of the Pathophysicologic Collagen Changes in the Diabetic Achilles Tendon.|
- Structural and metabolic changes [ Time Frame: 1 year ] [ Designated as safety issue: No ]Characterize the structural and metabolic changes in the diabetic Achilles tendon as related to limb loss.
- Relationship between collagen changes and system changes [ Time Frame: 1 year ] [ Designated as safety issue: No ]Describe the relationship between collagen changes and system changes in the diabetic patient.
Biospecimen Retention: Samples Without DNA
A tissue sample (20mg) of the Achilles tendon will be collected at this time. This tissue will be preserved in a dry ice container and shipped to Midwestern University for processing by the sub-investigator (CC). The specimens will be labeled numerically with a predetermined subject number. No patient identifying information will be on these samples.
|Study Start Date:||May 2011|
|Estimated Study Completion Date:||May 2015|
|Estimated Primary Completion Date:||May 2015 (Final data collection date for primary outcome measure)|
|Preulcerative plantar foot lesion|
Plantar ulcer no history of amputation
Plantar ulceration without a history of amputation or require an amputation.
Plantar ulcer and digital amputation
Plantar ulceration who will be undergoing a digital amputation.
Plantar ulcer and transmet amputation
Plantar ulceration who will be undergoing a transmetatarsal amputation.
Plantar ulceration and choparts
Plantar ulceration who will be undergoing Chopart's or more proximal amputation.
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Diabetes is a pandemic problem with catastrophic effects on the physical, psychological, and economic lives of patients and their families, and also places a significant burden on the healthcare system. Changes in the integumentary system lead to plantar foot ulcerations, which increase the risk of limb amputations and death. Specifically, limitation of ankle joint dorsiflexion (equinus deformity) has been implicated as a major deforming force in the development and chronicity of plantar foot ulcerations in the diabetic population. A better mechanistic understanding of the intrinsic changes in the diabetic Achilles tendon would assist in explaining and potentially preventing the development of chronic foot ulcerations due to an equinus deformity.
This study will evaluate the relationship between limb loss progression and changes seen in collagen metabolic markers in the diabetic Achilles tendon. This will be assessed by collecting Achilles tendon samples in subjects who are at various stages of ulcer development or limb loss and who also demonstrate an equinus deformity. All Achilles tendon samples will be collected at the time of the Achilles lengthening procedure. There will be five subject groups consisting of subjects who have been identified with: 1)preulcerative plantar foot lesion 2)plantar ulceration without a history of amputation or require an amputation 3) plantar ulceration who will be undergoing a digital amputation 4) plantar ulceration who will be undergoing a transmetatarsal amputation or 5) plantar ulceration who will be undergoing Chopart's or more proximal amputation. Further, systemic changes (vasculopathy, peripheral neuropathy, nephropathy) will also be correlated with the above. The independent variables are the following: 1) collagen metabolic markers and 2)systemic changes. The dependent variable is limb loss progression assessed categorically (5 groups).
The 5 phases of this study include:
- Phase 1- Eligibility Assessment. Type I and Type II diabetic patients who present to the Georgetown University Hospital Limb Salvage Center will be evaluated for inclusion into our study based on inclusion/exclusion criteria.
- Phase 2- Interview and examination. Subjects will complete a comprehensive medical history, physical exam, and blood work (per Standard of Care. The PI or SI will perform an ankle joint range of motion examination and a Semmes-Weinstein 5.07 monofilament examination (per Standard of Care. A comprehensive metabolic panel will be ordered including hemoglobin A1C, BUN, and CR (per Standard of Care). Patients will then be referred to the vascular surgery department for noninvasive and/or invasive vascular studies (per standard of care) and patient will be scheduled for surgery at this time.
- Phase 3- Surgery and Tissue Collection. Surgery will be performed that may include ulcer debridement, soft tissue or bone reconstruction, or amputation (per SOC- only patients who have been identified as demonstrating an equinus deformity and agree to an Achilles tendon lengthening procedure along with ulcer debridement, or soft tissue or bone reconstruction, or amputation will be included in this study. Achilles tendon lengthening is considered an adjunctive SOC procedure in the surgical management of the diabetic foot). All subjects will have an Achilles tendon lengthening procedure performed by the primary (PK) or sub-investigators (JS and CA). A tissue sample (20mg) of the Achilles tendon will be collected at this time. This tissue will be preserved in a dry ice container and shipped to Midwestern University for processing by the sub-investigator (CC). The specimens will be labeled numerically with a predetermined subject number. No patient identifying information will be on these samples.
- Phase 4- Tissue and Data Processing. Assays will be performed on the tissue samples to measure specific metabolic markers of the diabetic Achilles tendon. Tendon collagen concentrations will be determined via quantification of the collagen specific amino acid, hydroxyproline by high performance liquid chromatography (HPLC) and fluorometric detection. The extent of collagen cross-linking will be determined by measuring the amount of pyridinium cross-link hydroxylysylpyridinoline will also be assessed though HPLC. RT-PCR will also be performed to determine the expression of various MMPs and TIMPs. The blood markers will be processed at Georgetown University Hospital. The Department of Vascular Surgery at Georgetown University will perform the noninvasive and invasive studies and the results of their findings will be reported to the investigators.
- Phase 5-Data Analysis. The results from the physical examination, laboratory studies, vascular studies, and tissue assays will be collected and evaluated.
|Contact: Paul J. Kim, DPM||202-444-0469||Paul.email@example.com|
|Contact: John Steinberg, DPMfirstname.lastname@example.org|
|United States, District of Columbia|
|Georgetown University Hospital Center for Wound Healing||Recruiting|
|Washington, District of Columbia, United States, 20007|
|Contact: Paul J. Kim, DPM 202-444-0469 email@example.com|
|Contact: Mallory W Nichols, BS 202-444-0283 Mallory.Nichols@gunet.georgetown.edu|
|Principal Investigator: Paul J. Kim, DPM|
|Sub-Investigator: John Steinberg, DPM|
|Sub-Investigator: Christopher Attinger, MD|
|Sub-Investigator: Chad Carroll, PhD|
|Principal Investigator:||Paul J. Kim, DPM||Georgetown University Hospital|