A Phase 3 interventional study of Timolol and Non biologically active gel in Chronic Diabetic Foot Ulcers, Diabetic Neuropathic Ulcers and Non Healing Wound, sponsored by VA Office of Research and Development. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-05-08.
Sponsored by VA Office of Research and Development · Phase 3, Interventional, and Treatment
One in four Veterans is affected by diabetes and will develop a diabetic foot ulcer. Diabetic ulcers are very challenging to manage and are the most common cause of leg amputation. Many advanced treatments are expensive and difficult to use in the clinic or at home. Those newer therapies have shown little success in healing diabetic foot wounds. The investigators' laboratory and animal work has suggested that a safe medication, currently used as an eye drop for treatment of glaucoma, can heal these ulcers. The investigators are proposing to test this drop (timolol) directly on the surface of the foot ulcer to see if can improve healing faster than the current standard of care. To do this, the investigators propose a "randomized controlled trial" with two groups of patients with diabetic foot ulcers: one will receive standard of care with timolol while the other will receive standard of care with a gel (hydrogel, as placebo medicine).
The trial is designed as a prospective, randomized, double-blinded controlled study of subjects presenting with diabetic foot ulcers. The purpose of this study is to evaluate the superiority of Timoptic-XE therapy in conjunction with standard of care (SOC) treatment (Group A: Timoptic-XE + SOC) versus SOC (Group B: SOC + plus a non-biologically active gel, i.e., hydrogel, as placebo medication) in the clinical effectiveness in promoting wound healing and closure.
Lower extremity ulcer located anywhere on the foot (as defined as beginning below the malleoli of the ankle):
Exclusion Criteria:
Index ulcer shows evidence of infection (defined as a moderate or severe rating of all of the following clinical signs/symptoms:
Has received previous treatment with the following during the 60 days prior to Screening:
growth factors (epidermal growth factor, tumor necrosis factor, transforming growth factor, platelet derived growth factor, etc.)
Timoptic-XE plus standard of care (SOC)
Drug: Timolol
SOC plus non biologically active gel (hydrogel as placebo medication)
Drug: Non biologically active gel
Topical application of Timolol on non-healing diabetic foot ulcers
Also known as: Timoptic-XE
Topical application of non biologically active gel (Hydrogel- standard of care) on non-healing diabetic foot ulcers
Also known as: Hydrogel
Percentage of Complete Wound Closure, as Assessed Over a 12 Week Period
Complete wound closure will be assessed by Investigators and is defined as 100% epithelialization of the wound site ("skin re-epithelialization without drainage or dressing requirements by Week 12). The primary outcome was the proportion of patients with complete wound healing by the end of the treatment phase, evaluated using Fisher's exact test.
Time frame: 12 weeks
Safety Outcome Measurement of Timolol Serum
Safety outcome measurement of timolol serum during the treatment phase. Serum Timolol levels were assessed in all participants receiving SOC + Timolol. Most levels were below the detectable limit (\<0.22 ng/mL), suggesting minimal systemic absorption. Three participants exhibited detectable levels, with one case of a protocol deviation involving excessive application resulting in a serum level of 1.00 ng/mL. No systemic effects were observed in these cases, supporting the safety profile of topical Timolol.
Time frame: 12 weeks
The Time to Wound Closure Between the Two Groups
Time frame: 31 weeks
Recruitment started on July 24, 2018 and continued until August 30, 2023 from clinics at the VA Northern California Health Care System.
| Milestone | Timolol | SOC Plus Non Biologically Active Gel |
|---|---|---|
| Started | 21 | 27 |
| Completed | 21 | 24 |
| Not completed | 0 | 3 |
Complete wound closure will be assessed by Investigators and is defined as 100% epithelialization of the wound site ("skin re-epithelialization without drainage or dressing requirements by Week 12). The primary outcome was the proportion of patients with complete wound healing by the end of the treatment phase, evaluated using Fisher's exact test.
| Participants | Timolol | SOC Plus Non Biologically Active Gel |
|---|---|---|
| Percentage of Complete Wound Closure, as Assessed Over a 12 Week Period | 8 | 7 |
Safety outcome measurement of timolol serum during the treatment phase. Serum Timolol levels were assessed in all participants receiving SOC + Timolol. Most levels were below the detectable limit (\<0.22 ng/mL), suggesting minimal systemic absorption. Three participants exhibited detectable levels, with one case of a protocol deviation involving excessive application resulting in a serum level of 1.00 ng/mL. No systemic effects were observed in these cases, supporting the safety profile of topical Timolol.
| ng/ml | Timolol | SOC Plus Non Biologically Active Gel |
|---|---|---|
| Safety Outcome Measurement of Timolol Serum | 0.596 ± 0.315 | — |
| weeks | Timolol | SOC Plus Non Biologically Active Gel |
|---|---|---|
| The Time to Wound Closure Between the Two Groups | 5.8 ± 1.0 | 9.2 ± 1.0 |
Collected over 5 years. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Timolol | 2/21 (9.5%) | 0/21 (0%) | 0/21 (0%) |
| SOC Plus Non Biologically Active Gel | 5/27 (18.5%) | 2/27 (7.4%) | 0/27 (0%) |
| Event | Timolol | SOC Plus Non Biologically Active Gel |
|---|---|---|
| InfectionInfections and infestations | 0/21 | 1/27 |
| LightheadednessMetabolism and nutrition disorders | 0/21 | 1/27 |
| Age, Continuous(years) | Timolol | SOC Plus Non Biologically Active Gel | Total |
|---|---|---|---|
| Mean | 68 ± 8 | 67 ± 8 | 68 ± 8 |
| Sex: Female, Male(Participants) | Timolol | SOC Plus Non Biologically Active Gel | Total |
|---|---|---|---|
| Female | 1 | 0 | 1 |
| Male | 20 | 27 | 47 |
| Race (NIH/OMB)(Participants) | Timolol | SOC Plus Non Biologically Active Gel | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 1 | 0 | 1 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 4 | 5 | 9 |
| White | 16 | 19 | 35 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 3 | 3 |
| Region of Enrollment(Participants) | Timolol | SOC Plus Non Biologically Active Gel | Total |
|---|---|---|---|
| United States | 21 | 27 | 48 |
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VA Office of Research and Development