E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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.
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10050712 |
E.1.2 | Term | Vitamin A |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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.
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E.2.2 | Secondary objectives of the trial |
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.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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.
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E.4 | Principal 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.
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E.5 End points |
E.5.1 | 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 significant risk factors for the development of foot ulceration).
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The last visit of the last subject undergoing the trial. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |