Effect of Adiposity and Associated Local Microbial Factors on Healing and Progression of Diabetic Foot Ulcers

Study Overview
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Brief Summary
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Diabetic foot ulcers (DFUs) and their associated complications like amputations are increasingly becoming a problem in low and middle income (LMI) countries. Obesity (increased body fat/adiposity), which has been shown to complicate many diseases, is also increasing in LMI setting. It is however not certain whether increased adiposity, may make it difficult for DFUs to heal. Investigators aim to understand whether increased adiposity and accompanied local microbial factors have any negative impact on healing and progression of DFUs.

Detailed Description
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A prospective cohort of 300 individuals with type 2 diabetes presenting with diabetic foot ulcers (DFUs) at an outpatient clinic will be recruited. At baseline, participants will be stratified into normal and high adiposity groups as measured by Bioelectrical Impedance Analysis (BIA). Both groups will receive DFU management according to locally appropriate standards of care and followed-up for 24 weeks or until complete wound healing, whichever occurs first. Local microbial characteristics, presence or absence of infection and other clinical parameters will also be assessed, and compared between the two groups. Enrolling 150 participants per group will have a minimum power of 80% to detect a 20% difference in cumulative incidence of complete ulcer healing (at the 5% level of statistical significance) between the normal and high adiposity groups.

Official Title
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Prospective Exploration of the Effect of Adiposity and Associated Microbial Factors on the Healing and Progression of Diabetic Foot Ulcers in Tanzania

Conditions
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Diabetic Foot Ulcer

Intervention / Treatment
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* Other: Normal standard care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: History of type 2 diabetes mellitus (T2DM) Presence of participant's signed informed consent Age 30 years and above at the time the participant is signing the consent Tanzanians of African origin (Black Tanzanians) Presence of diabetic foot ulcer (DFUs) (new or recurrent) Exclusion Criteria: Known patients with congestive cardiac and/or renal failure. Any patients with absolute or relative contraindication for tissue biopsy (for incident cases) Patients with obvious signs of gangrene DFU patients with non-healing ulcer of more than 52 weeks duration. DFU patients with below normal body mass index BMI (BMI below 18).

Ages Eligible for Study
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Minimum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Normal adiposity group<br>Body fat < 25% and <32% in men and women respectively, will be categorized as high adiposity. This is according to the The American Council on Exercise criteria. | Other: Normal standard care<br>* Both groups will receive standardized treatment and care for diabetic foot ulcers<br>|
| High adiposity group<br>Body fat ≥ 25% and ≥32% in men and women respectively, will be categorized as high adiposity. This is according to the The American Council on Exercise criteria. | Other: Normal standard care<br>* Both groups will receive standardized treatment and care for diabetic foot ulcers<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion (%) of patients with complete wound healing at 24 weeks | Complete healing will be defined based on the criteria of the wound healing society, as 100% re-epithelialization of the wound surface (complete wound closure) with a complete absence of drainage. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with worsening or improving ulcer progression (worsening of improving based on University of Texas ulcer grading system) | Proportion (%) of patients with unfavorable progression (worsening) of an ulcer to a more advanced stage/grade or favorable progression (improving) of an ulcer to an earlier stage/grade, among those enrolled into the study within the study time frame. The grades will be evaluated using the University of Texas ulcer grading system. | 24 weeks | 
| Proportion of patients ending up in amputation | Proportion (%) of patients getting amputations of a toe or foot on the same side as an index ulcer, among those enrolled into the study within the study time frame. | 24 weeks | 
| Proportion of patients who Die | Proportion (%) of patients who die among those enrolled into the study within the study time frame | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adiposity, Diabetic foot ulcer, Anti-microbial resistance