Safety Study of Topical Doxycycline Gel for Adult Diabetic Lower Extremity Ulcers

Study Overview
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Brief Summary
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This study is a double-blind, one center, two-arm study with a two (2) week Run-In, evaluating the efficacy of a once-daily administration of NanoDOX™ Hydrogel topically applied to diabetic ulcers in concert with professionally administered Standard of Care (SOC) procedures as described by Standard Operating Procedure(s) of the Department of Veterans Administration Hospitals. During the run-in period patients with infected wounds will receive oral antibiotic and not be included in the topical portion of the study until the infection is shown by wound fluid analysis to be resolved. Following a two (2) week Run-In of all patients to receive SOC treatment for diabetic ulcers, patients would have either the investigational material or the placebo hydrogel applied as a part of their wound care. Each patient would receive 1.5 gm packets of either the test article or the placebo hydrogel for a once-daily home treatment accompanied by a dressing change.

Detailed Description
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Study of NanoDOX vs placebo on diabetic ulcers of the lower leg/foot.

Official Title
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A Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of NanoDOX™ Hydrogel(1.0% Doxycycline Monohydrate)in Diabetic Adult Subjects With Lower Extremity Ulcers Compared to Placebo Hydrogel.

Conditions
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Diabetic Foot Ulcer

Intervention / Treatment
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* Drug: doxycycline
* Drug: placebo gel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a documented history of type I or type II diabetes mellitus as defined by the American Diabetes Association Women of childbearing potential must have a negative urine pregnancy test at screening and at baseline, and: • Agree to use a double-barrier method of contraception during their participation in this study; condoms (with spermicide) and hormonal contraceptives OR condoms (with spermicide) and intrauterine device OR intrauterine device and hormonal contraceptives OR Abstains from sexual intercourse during their participation in this study OR Is with a same-sex partner and does not participate in bisexual activities where there is a risk of becoming pregnant Have an ulcer on the lower extremity (distal to a line connecting the medial and lateral malleoli) that has been present for at least 3 weeks and that is 1.2 cm2 to 4.0 cm2 at initial screening Be able to apply study drug to their ulcer, or have a caregiver do it Adequate blood flow to target ulcer extremity as measured by transcutaneous oxygen tension (TcpO2) of >30mmHg Target ulcer is Grade I according to the Wagner Grading Scale Quantitative bacterial count of of < 1.0 x 1.0E5 per gram of tissue for non-infected ulcers Quantitative bacterial count of ≥ 1.0 x 1.0E5 per gram of tissue for infected ulcers Exclusion Criteria: Be a pregnant or lactating woman or a female of childbearing potential who is not practicing acceptable form of birth control. Allergy to tetracycline, minocycline, demeclocycline, or any other known tetracycline derivative Have more than three chronic ulcers present at baseline Have undergone treatment with system corticosteroid or immunosuppressive therapy in the past 2 months Have connective tissue disease Currently be going through kidney dialysis for renal failure Have undergone treatment with doxycycline, Procuren®, or Regranex® within the last 30 days Have participated in another clinical research trial within the last 30 days Have a known history of osteomyelitis affecting to the area where the target ulcer is present Have any other concomitant condition which, in the opinion of the investigator, would make the subject unsuitable for the study. Subject has ulcers resulting from any cause other than diabetes (electrical burn, arterial insufficiency, chemical or radiation insult)

Ages Eligible for Study
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Minimum Age: 18 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NanoDOX™ Hydrogel<br>1.0% doxycycline gel | Drug: doxycycline<br>* 1.0% doxycycline gel applied topically to the wound once daily for 20 weeks<br>|
| Placebo Comparator: Placebo<br>placebo gel | Drug: placebo gel<br>* placebo gel applied topically to the wound once daily for 20 weeks<br>* Other names: doxycycline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Without Adverse Events | Participants were monitored for 20 weeks during the study. | every 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Analyze the Molecular Changes in Pro-inflammatory Cytokine Levels That Occur in Diabetic Foot Ulcers as a Function of Healing Rate in the Presence /Absence of NanoDOX Hydrogel (1% Doxycycline Monohydrate Gel) |  | baseline, week 4, week 10, week 20 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetic, Ulcer, Wound