Trial Outcomes & Findings for Beta Adrenergic Antagonist for the Healing of Chronic DFU (NCT NCT03282981)

Last Updated: 2025-05-08

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

48 participants

Primary outcome timeframe

12 weeks

Results posted on

2025-05-08

Participant Flow

Recruitment started on July 24, 2018 and continued until August 30, 2023 from clinics at the VA Northern California Health Care System.

Participant milestones

Participant milestones
Measure	Timolol Timoptic-XE plus standard of care (SOC) Timolol: Topical application of Timolol on non-healing diabetic foot ulcers	SOC Plus Non Biologically Active Gel SOC plus non biologically active gel (hydrogel as placebo medication) Non biologically active gel: Topical application of non biologically active gel (Hydrogel- standard of care) on non-healing diabetic foot ulcers
Overall Study STARTED	21	27
Overall Study COMPLETED	21	24
Overall Study NOT COMPLETED	0	3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Beta Adrenergic Antagonist for the Healing of Chronic DFU

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Timolol n=21 Participants Timoptic-XE plus standard of care (SOC) Timolol: Topical application of Timolol on non-healing diabetic foot ulcers	SOC Plus Non Biologically Active Gel n=27 Participants SOC plus non biologically active gel (hydrogel as placebo medication) Non biologically active gel: Topical application of non biologically active gel (Hydrogel- standard of care) on non-healing diabetic foot ulcers	Total n=48 Participants Total of all reporting groups
Age, Continuous	68 years STANDARD_DEVIATION 8 • n=5 Participants	67 years STANDARD_DEVIATION 8 • n=7 Participants	68 years STANDARD_DEVIATION 8 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Sex: Female, Male Male	20 Participants n=5 Participants	27 Participants n=7 Participants	47 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) White	16 Participants n=5 Participants	19 Participants n=7 Participants	35 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment United States	21 Participants n=5 Participants	27 Participants n=7 Participants	48 Participants n=5 Participants

PRIMARY outcome

Timeframe: 12 weeks

Population: chronic, diabetic foot ulcerations

Outcome measures

Outcome measures
Measure	Timolol n=21 Participants Timoptic-XE plus standard of care (SOC) Timolol: Topical application of Timolol on non-healing diabetic foot ulcers	SOC Plus Non Biologically Active Gel n=27 Participants SOC plus non biologically active gel (hydrogel as placebo medication) Non biologically active gel: Topical application of non biologically active gel (Hydrogel- standard of care) on non-healing diabetic foot ulcers
Percentage of Complete Wound Closure, as Assessed Over a 12 Week Period	8 Participants	7 Participants

PRIMARY outcome

Timeframe: 12 weeks

Population: safety level measure of serum timolol

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.

Outcome measures

Outcome measures
Measure	Timolol n=21 Participants Timoptic-XE plus standard of care (SOC) Timolol: Topical application of Timolol on non-healing diabetic foot ulcers	SOC Plus Non Biologically Active Gel SOC plus non biologically active gel (hydrogel as placebo medication) Non biologically active gel: Topical application of non biologically active gel (Hydrogel- standard of care) on non-healing diabetic foot ulcers
Safety Outcome Measurement of Timolol Serum	0.596 ng/ml Standard Deviation 0.315	—

SECONDARY outcome

Timeframe: 31 weeks

Population: chronic diabetic foot ulcer

Outcome measures

Outcome measures
Measure	Timolol n=21 Participants Timoptic-XE plus standard of care (SOC) Timolol: Topical application of Timolol on non-healing diabetic foot ulcers	SOC Plus Non Biologically Active Gel n=27 Participants SOC plus non biologically active gel (hydrogel as placebo medication) Non biologically active gel: Topical application of non biologically active gel (Hydrogel- standard of care) on non-healing diabetic foot ulcers
The Time to Wound Closure Between the Two Groups	5.8 weeks Standard Deviation 1.0	9.2 weeks Standard Deviation 1.0

Adverse Events

Timolol

Serious events: 0 serious events

Other events: 0 other events

Deaths: 2 deaths

SOC Plus Non Biologically Active Gel

Serious events: 2 serious events

Other events: 0 other events

Deaths: 5 deaths

Serious adverse events

Serious adverse events
Measure	Timolol n=21 participants at risk Timoptic-XE plus standard of care (SOC) Timolol: Topical application of Timolol on non-healing diabetic foot ulcers	SOC Plus Non Biologically Active Gel n=27 participants at risk SOC plus non biologically active gel (hydrogel as placebo medication) Non biologically active gel: Topical application of non biologically active gel (Hydrogel- standard of care) on non-healing diabetic foot ulcers
Infections and infestations Infection	0.00% 0/21 • 5 years	3.7% 1/27 • Number of events 1 • 5 years
Metabolism and nutrition disorders Lightheadedness	0.00% 0/21 • 5 years	3.7% 1/27 • Number of events 1 • 5 years

Other adverse events

Adverse event data not reported

Additional Information

Dr. Sara Dahle and Dr. Rosyln Rivkah Isseroff

VA Northern California Health Care System

Phone: 916-843-7151

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place