Chronic Diabetic Foot UlcersPhase 3BAART-DFUNCT03282981
Beta Adrenergic Antagonist for the Healing of Chronic DFU
A Phase 3 study testing Timolol and Non biologically active gel in people with Chronic Diabetic Foot Ulcers and Diabetic Neuropathic Ulcers, run by VA Office of Research and Development at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Diabetic Foot Ulcers, Diabetic Neuropathic Ulcers, Non Healing Wound
- What is being tested?
- Timolol and Non biologically active gel
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Jul 2018to 30 Apr 2024
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female subject of any race 18 years old or older
- Lower extremity ulcer located anywhere on the foot (as defined as beginning below the malleoli of the ankle):
- Of more than 30 days duration and less than 2 years duration
- Surface area between 0.5cm2 and 20cm2 (as measured with the Silhouette imaging system at randomization). The ulcer with largest surface area meeting inclusion criteria will be selected as index ulcer
- If two ulcers present with the same surface area, the ulcer of the longest duration will be selected as index ulcer
- Documented Ankle Brachial Index (ABI) between 0.8 and 1.2 on the study limb or toe pressure over 65mmHg within 3 months of screening phase
Show all 9Show fewer
- Documented biopsy report to rule out malignancy of ulcer of > 6 months duration
- Subject or legally authorized representative understands and is willing to give written informed consent
- Subject or legally authorized representative is willing and able to comply with a trial (13 to 17 days) of protocol-specified standard care prior to randomization and to comply with all study requirements
Who cannot join
- Ulcer of non-diabetic etiology, such as venous, arterial and burn wounds
- Index ulcer is less than 3 cm in distance from any other ulcer on the same extremity
- There are greater than 3 ulcers on the study foot
- Index ulcer presents with any of the following: cellulitis, osteomyelitis, exposed bone, tendon or fascia, capsule , purulent exudate or gangrene
- Index ulcer shows evidence of infection (defined as a moderate or severe rating of all of the following clinical signs/symptoms:
- increased warmth
Show all 28Show fewer
- increased pain
- erythema
- malodorous exudate at Screening or at Randomization (Visit 1), OR total organism count > 1 x 105 colony forming units (CFU) from the screening visit study ulcer culture sample)
- Index ulcer surface area has decreased or increased > 40% between Screening and at Randomization (Visit 1) as assessed by the Silhouette imaging system
- Has acquired or is known to be infected with Human Immunodeficiency Virus (HIV)
- Has active malignancy on the study foot
- Has uncontrolled diabetes mellitus as defined by glycosylated hemoglobin A1C > 12%
- Has immunodeficiency as defined by serum IgG, IgA, and IgM less than one-half the lower limit of normal
- Has severe protein malnutrition as defined by serum albumin < 2.5 g/dL
- Has serum aspartate aminotransferase (AST, SGOT, GOT) or serum alanine aminotransferase (ALT, SGPT, GPT) levels greater than twice the upper limit of normal
- Has fatigue, palpitations, dyspnea, and/or angina at rest
- Has a history, within the previous 12 months from date of Screening Visit, of alcohol or drug abuse, particularly methadone or heroin
- Has received previous treatment with the following during the 60 days prior to Screening:
- Immunosuppressive agents
- radiation
- chemotherapy
- growth factors (epidermal growth factor, tumor necrosis factor, transforming growth factor, platelet derived growth factor, etc.)
- at the site of the study ulcer, split- or full-thickness skin graft at the site of the study ulcer, biologically-active (or engineered) cellular or acellular product(s) at the site of the study ulcer, investigational drug or device
- Has been hospitalized for treatment of a diabetic foot ulcer within the previous 30 days from Screening
- Has history of heart block 2nd and 3rd degree
- Female who is pregnant or refuses to use adequate contraceptive methods and is of childbearing age during the trial
- Prisoners, institutionalized individuals or vulnerable population
Trial locations and contacts
1 site in 1 country.
United States1 site
VA Northern California Health Care System, Mather, CA
Sacramento, California, 95655-4200
About this study
Official title: Beta Adrenergic Antagonist For The Healing of Chronic Diabetic Foot Ulcers
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).
Read the detailed description
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.
- Being tested
- Timolol, Non biologically active gel
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TimololDrug
Also called Timoptic-XE
Topical application of Timolol on non-healing diabetic foot ulcers
Non biologically active gelDrug
Also called Hydrogel
Topical application of non biologically active gel (Hydrogel- standard of care) on non-healing diabetic foot ulcers
| Study group | Role | What they receive |
|---|---|---|
| Timolol | Experimental | Timoptic-XE plus standard of care (SOC) Receives: Drug: Timolol |
| SOC plus non biologically active gel | Placebo comparator | SOC plus non biologically active gel (hydrogel as placebo medication) Receives: Drug: Non biologically active gel |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 12 weeks
Secondary outcomes (1)
The Time to Wound Closure Between the Two Groups
Measured: 31 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2017
- Study start24 Jul 2018
- Primary completion1 Dec 2023
- Study completion30 Apr 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Diabetic Foot UlcersStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Collaborators
- VA Northern California Health Care System
- Responsible party
- Sponsor
- Investigators
- Sara E. Dahle, DPM MPH, Principal investigator, VA Northern California Health Care System, Mather, CARivkah R. Isseroff, MD, Principal investigator, VA Northern California Health Care System, Mather, CA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03282981
- Sponsor's protocol ID
- SURG-004-16F
- Other IDs
- 17-08-00792
- Acronym
- BAART-DFU
- Status last verified
- Apr 2025
- First submitted
- 12 Sep 2017
- Last updated
- 8 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kaur R, Tchanque-Fossuo C, West K, Hadian Y, Gallegos A, Yoon D, Ismailyan L, Schaefer S, Dahle SE, Isseroff RR. Beta-adrenergic antagonist for the healing of chronic diabetic foot ulcers: study protocol for a prospective, randomized, double-blinded, controlled and parallel-group study. Trials. 2020 Jun 8;21(1):496. doi: 10.1186/s13063-020-04413-z.
PubMed 32513257
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Beta Adrenergic Antagonist For The Healing of Chronic Diabetic Foot Ulcers
- ClinicalTrials.gov ID
- NCT03282981
- Acronym / sponsor ID
- BAART-DFU / SURG-004-16F
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Collaborators
- VA Northern California Health Care System
- Study start
- 24 Jul 2018 (actual)
- Primary completion
- 1 Dec 2023 (actual)
- Study completion
- 30 Apr 2024 (actual)
- First posted
- 14 Sep 2017 (actual)
- Results
- Posted 25 Apr 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Timolol | Experimental | Drug: TimololTimoptic-XE plus standard of care (SOC) |
| SOC plus non biologically active gel | Placebo comparator | Drug: Non biologically active gelSOC plus non biologically active gel (hydrogel as placebo medication) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Male or female subject of any race 18 years old or older
- Lower extremity ulcer located anywhere on the foot (as defined as beginning below the malleoli of the ankle):
- Documented Ankle Brachial Index (ABI) between 0.8 and 1.2 on the study limb or toe pressure over 65mmHg within 3 months of screening phase
- Documented biopsy report to rule out malignancy of ulcer of > 6 months duration
- Subject or legally authorized representative understands and is willing to give written informed consent
Key exclusion criteria (28 listed)
- Ulcer of non-diabetic etiology, such as venous, arterial and burn wounds
- Index ulcer is less than 3 cm in distance from any other ulcer on the same extremity
- There are greater than 3 ulcers on the study foot
- Index ulcer presents with any of the following: cellulitis, osteomyelitis, exposed bone, tendon or fascia, capsule , purulent exudate or gangrene
- Index ulcer shows evidence of infection (defined as a moderate or severe rating of all of the following clinical signs/symptoms:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TimololAlso: Timoptic-XETopical application of Timolol on non-healing diabetic foot ulcers | Drug | Timolol |
| Non biologically active gelAlso: HydrogelTopical application of non biologically active gel (Hydrogel- standard of care) on non-healing diabetic foot ulcers | Drug | SOC plus non biologically active gel |
Primary outcome
Percentage of Complete Wound Closure, as Assessed Over a 12 Week Period
Time frame: 12 weeks
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.
Safety Outcome Measurement of Timolol Serum
Time frame: 12 weeks
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.
1 secondary outcome
The Time to Wound Closure Between the Two Groups
Time frame: 31 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32513257Kaur R, Tchanque-Fossuo C, West K, Hadian Y, Gallegos A, Yoon D, Ismailyan L, Schaefer S, Dahle SE, Isseroff RR. Beta-adrenergic antagonist for the healing of chronic diabetic foot ulcers: study protocol for a prospective, randomized, double-blinded, controlled and parallel-group study. Trials. 2020 Jun 8;21(1):496. doi: 10.1186/s13063-020-04413-z.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sara E. Dahle, DPM MPH principal investigator
VA Northern California Health Care System, Mather, CA
Rivkah R. Isseroff, MD principal investigator
VA Northern California Health Care System, Mather, CA
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Timolol and Non biologically active gel in people with Chronic Diabetic Foot Ulcers and Diabetic Neuropathic Ulcers, run by VA Office of Research and Development at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Apr 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Complete Wound Closure, as Assessed Over a 12 Week Period (time frame: 12 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03282981, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2025.