The overall goal of the proposal is to assess the capacity of topical retinoid treatment to induce changes in connective tissue metabolism (i.e., increased collagen production and decreased elaboration of matrix metalloproteinases [MMPs]) in the skin of diabetic patients. MedDRA version: 9.1 Level: LLT Classification code 10050712 Term: Vitamin A
Conditions
Interventions
Product Name: Tretinoin
Product Code: Retinoic acid
Pharmaceutical Form: Cream
INN or Proposed INN: Tretinoin
CAS Number: 302-79-4
Sponsors
University of Birmingham
Birmingham Heartlands Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Type 1 or Type 2 Diabetes as defined by the World Health Organisation classification. 2. Age between 18-70 years. 3. Women of child bearing potential must be using an acceptable method of contraception to prevent pregnancy when they are enrolled in the study and must agree to continue to practice an acceptable method of contraception for the duration of their participation in the study. 4. Must meet the specified criteria for diabetic neuropathy and have no risk factors for other causes of neuropathy 5. Willingness to sign the Centre for Research Ethics Committee (COREC) approved informed consent form. 6. The presence of microalbuminurea and/or retinopathy. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Nursing mothers, pregnant women (excluded by a negative pregnancy test). 2. Patients with a history of drug or alcohol dependence within the last 5 years. 3. Patients with severe systemic disease other than diabetes which has a recognized complication of neuropathy. 4. Patients with a history of previous kidney, pancreas or cardiac transplantation. 5. Serious or unstable medical or psychological state that may interfere with study participation. 6. Patients having taken part in another investigational drug study within the last three months. 7. Patients who refuse to sign the informed consent form. 8. Patients with pre-existing generalized skin conditions which might affect skin structure or function such as eczema, psoriasis. 9. Patients who are on long term steroid or immunosuppressive therapy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To conduct a 16 week study in which subjects with diabetes at risk for development of lower limb ulcers are treated topically with RA or vehicle on hip skin to determine if topical retinoid therapy improves collagen structure. ; Secondary Objective: To conduct a 16 week study in which subjects with diabetes at risk for development of lower limb ulcers are treated topically with RA or vehicle on hip skin to determine if topical retinoid therapy improves the overall quality of the skin. ; Primary end point(s): Topical retinoid treatment and biopsy protocol. Volunteers are treated topically for 16 wks with 0.025% RA and its vehicle or vehicle alone on the opposite thighs. At the initial assessment, 3-mm biopsies will be obtained from each thigh of each participant. The RA and vehicle are then applied 3x per week.Volunteers will be provided ith plastic spatulas to aid dispensing study medication. At 16 wk, triplicate 3-mm punch biopsies from the RA-treated and vehicle-treated skin are obtained. Comparison between the 2 groups of biopsies will allow assessment of the effects of treatment on collagen structure and synthesis and MMP/MMP inhibitor elaboration and epidermal nerve fiber counts. One biopsy from each site is frozen in OCT for immunohistochemical analysis of types I and III procollagen production and for elaboration of MMPs and MMP inhibitors (MMP-1, MMP-9 and TIMP-1). The second biopsy is fixed in 2% glutaraldehyde for assessment of collagen structure at the light and electron microscopic (EM) levels. The third biopsy is fixed for 12-18 h in paraformaldehyde-lysine-periodate and cryprotected overnight (20% glycerol/20% 0.4 M Sorrenson buffer) at 40C and cut into 50 mm sections with a freezing microtome for assessment of epidermal nerve fibre density. Direct comparisons are performed between Groups 1 and 2 (i.e., the responses of skin from diabetic individuals with and without signif | — |
Countries
United Kingdom
Outcome results
None listed