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

Phase 2

Completed

Brief Summary: 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: Study of NanoDOX vs placebo on diabetic ulcers of the lower leg/foot.

Recruitment & Eligibility

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)

Arm && Interventions

Group	Intervention	Description
Placebo	placebo gel	placebo gel
NanoDOX™ Hydrogel	doxycycline	1.0% doxycycline gel

Primary Outcome Measures

Name	Time	Method
Number of Participants Without Adverse Events	every 2 weeks	Participants were monitored for 20 weeks during the study.

Secondary Outcome Measures

Name	Time	Method
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