Beta Adrenergic Antagonist for the Healing of Chronic DFU

NCT03282981 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: SURG-004-16F17-08-00792
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief 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. 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).

Conditions

Chronic Diabetic Foot Ulcers; Diabetic Neuropathic Ulcers; Non Healing Wound

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  12 weeks

Secondary Outcomes (1)

• The Time to Wound Closure Between the Two Groups

  31 weeks

Study Arms (2)

Timolol

EXPERIMENTAL

Timoptic-XE plus standard of care (SOC)

Drug: Timolol

SOC plus non biologically active gel

PLACEBO COMPARATOR

SOC plus non biologically active gel (hydrogel as placebo medication)

Drug: Non biologically active gel

Interventions

Timolol DRUG

Topical application of Timolol on non-healing diabetic foot ulcers

Also known as: Timoptic-XE

Timolol

Non biologically active gel DRUG

Topical application of non biologically active gel (Hydrogel- standard of care) on non-healing diabetic foot ulcers

Also known as: Hydrogel

SOC plus non biologically active gel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• VA Office of Research and Development: lead
• VA Northern California Health Care System: collaborator

Study Sites (1)

VA Northern California Health Care System, Mather, CA

Sacramento, California, 95655-4200, United States

Location

Related Publications (1)

• 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.

  PMID: 32513257 DERIVED

MeSH Terms

Interventions

Timolol; Hydrogels

Intervention Hierarchy (Ancestors)

Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Thiadiazoles; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Morpholines; Oxazines; Gels; Colloids; Complex Mixtures; Dosage Forms; Pharmaceutical Preparations

Results Point of Contact

• Title: Dr. Sara Dahle and Dr. Rosyln Rivkah Isseroff
• Organization: VA Northern California Health Care System

sara.dahle@va.gov

916-843-7151

Study Officials

• Sara E. Dahle, DPM MPH

  VA Northern California Health Care System, Mather, CA

  PRINCIPAL INVESTIGATOR

• Rivkah R. Isseroff, MD

  VA Northern California Health Care System, Mather, CA

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2017
• First Posted: September 14, 2017
• Study Start: July 24, 2018
• Primary Completion: December 1, 2023
• Study Completion: April 30, 2024
• Last Updated: May 8, 2025
• Results First Posted: April 25, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)