Diabetic Foot UlcerPhase 2NCT04723134
Evaluation of a Folic Acid Wound Treatment (FAWT) for Chronic, Early-Stage Diabetic Foot Ulcer (DFU) Healing
A Phase 2 study testing Folinic acid calcium salt in people with Diabetic Foot Ulcer, run by Joseph Boykin, MD at 1 site in United States.
Trial summary
This is a twelve-week single-center, randomized, double-blind, clinical study to evaluate the safety and efficacy of a folic acid wound treatment (FAWT) versus Placebo in the promotion of healing of chronic, early stage diabetic foot ulcer (ES-DFU) wounds. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetic Foot Ulcer
- What is being tested?
- Folinic acid calcium salt
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Dec 2021to 24 Sep 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- Study subjects will be male or female Veterans with T2DM managed with insulin and/or non-insulin therapy who have a chronic, non-healing DFU (wound age: at least 4-weeks) and who have signed an Institutional Review Board approved informed consent document.
- Study subject candidates (SC) - may present with multiple DFUs; however, only one DFU per SC will be selected for study. A DFU-SC must be observed with: 1) at least a four-week history of a non-healing, superficial DFU-wound; PEDIS-Grade 1 or 2 Depth (wound above fascia without exposed muscle, tendon or bone); 2) DFU-wound area between 1-12cm2; 3) DFU-wound with or without clinical neuropathy; 4) DFU-wound lower extremity non-invasive Doppler studies with ankle-brachial index value ≥0.7 and/or Toe pressure ≥50mmHg; and, 5) without evidence of acute infection (e.g., cellulitis, abscess or osteomyelitis) at the time of enrollment.
- If the subject is a woman of childbearing potential she must be practicing an acceptable form of birth control, as determined by the Investigator. All females with an intact uterus must have a negative Beta-Human Chorionic Gonadotropin test (< 5mIU/mL) to proceed with study participation.
Who cannot join
- Any SC who is unable to provide written informed consent will not be enrolled for study participation.
- Any SC who is pregnant or breast feeding, will not be allowed to enroll, or continue, in the study, as pregnancy or breast feeding may impact the study results.
- Subjects with DFU-wounds less than 1cm-square or greater than 12cm-square will be excluded from the study.
- At the beginning of the four-week Screening Phase all SC will be scheduled for study-selected standard DFU wound treatment and off-loading of the study ulcer, as determined by the PI. Subject candidates who are unable to comply with the recommended off-loading of the selected DFU-study wound will be excluded from study.
- During the Screening Phase, any SC whose DFU wound demonstrates more than a fifty-percent (50%) reduction in wound area will be excluded from the study [37].
- Any SC with a current active history of alcohol or substance abuse will be excluded from study participation.
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- Any SC receiving steroid therapy (prednisone), chemotherapy or biological therapies (e.g., Humira) within twelve-weeks will be excluded.
- Any SC with active cancerous lesions, with or without chemotherapy, will be excluded from study participation.
- Any SC having received hyperbaric oxygen therapy (HBOT) or the use of bioengineered skin substitutes (i.e., Dermagraft® or Apligraf®) within six-months will be excluded from study participation.
- Any SC receiving platelet-derived growth factor therapy (Regranex®, Ortho- McNeil) within six-months will be excluded from study participation.
- Any SC who is on dialysis (hemo- or peritoneal dialysis) or has end stage renal disease will be excluded from study participation.
- A SC with ABI values <0.7 or toe pressure <50mmHg, for the involved lower extremity of the study DFU-wound, will be excluded from study participation.
- A SC with a HgbA1C >9 will be excluded from study participation.
- Any SC with a medical condition, which, in the opinion of the investigator should exclude him/her from participating in the study.
- Any SC previously taking daily oral high-dose folic acid with B-vitamin supplements (HDFA; folic acid-5mg/cyanocobalamin- 4mg/pyridoxine-50mg) for DFU-wound treatment will not be considered for study participation until at least 28-days following the discontinuation of HDFA administration.
Trial locations and contacts
1 site in 1 country.
United States1 site
Hunter Holmes McGuire VAMC
Richmond, Virginia, 23249
About this study
Official title: Development of a Novel Folic Acid Wound Dressing to Enhance Nitric Oxide Bioactivity Required for Diabetic Foot Ulcer Wound Healing
This is a twelve-week single-center, randomized, double-blind, clinical study to evaluate the safety and efficacy of a folic acid wound treatment (FAWT) versus Placebo in the promotion of healing of chronic, early stage diabetic foot ulcer (ES-DFU) wounds. Male and female Veterans with type-2 diabetes mellitus and chronic ES-DFUs acceptable to the study inclusion/exclusion criteria will be considered for enrollment.
Read the detailed description
This clinical study is a twelve-week single-center, randomized, double-blind evaluation of the safety and efficacy of a folic acid wound treatment (FAWT) versus Placebo in the promotion of healing of chronic (greater than 4-weeks), early stage diabetic foot ulcer (ES-DFU) wounds (PEDIS-Grade 1 or 2 Depth - wound above fascia without exposed muscle, tendon or bone). Study wound areas will be between 1.0 and 12.0 cm-square.
The chronic, non-healing DFU is a serious and common complication of diabetes. Chronic DFU complications are among the most frequent diabetes-related diagnoses for hospitalization and the leading cause of diabetes-associated lower limb amputations. Increased levels of the tumor suppressor protein p53 in wound keratinocytes from non-healing DFUs suggests increased cell death due to significant (p<0.05) transcription factor activation. Treatment with high dose folic acid (5mg/day) correlates to improved healing in ES-DFU wounds, perhaps by improving folate/methionine metabolism which provides support for DNA repair, the generation of reductive equivalents and regulates DNA methylation, an important epigenetic regulator of p53 transcription activity. Folinic acid calcium salt (calcium folinate) is the bioactive metabolite of folic acid that does not require reduction by dihydrofolate reductase (DHFR). In this study, FAWT (2.5-percent by weight) is provided by compounding 1.25-gms of folinic acid calcium salt with 50-gms of the Placebo (Plurogel Burn and Wound Dressing™, Medline Industries, Inc.). Experimental studies of topical folinic acid demonstrate significant improvements in wound healing parameters with decreased cellular markers of inflammation and increased active signaling of tissue repair. Topical administration of FAWT removes the potential for the adverse impact of high blood folate levels observed with oral high dose folic acid, that could include an increase in the occurrence of sub-classes of colon or prostate cancer.
The study hypothesis is that during a twelve-week evaluation period FAWT may provide significant (p<0.05) improvements, as compared to Placebo, in the rate of healing and complete closure (re-epithelialization) of chronic ES-DFU wounds.
The study will have two phases: Screening and Treatment.
The Screening Phase (first 4 weeks) is designed to determine if male and female Veterans selected as study participants are eligible to proceed to the Treatment Phase of the study. This phase consists of screening assessments that will include evaluation of the rate of study wound closure while the participants receive standard of care (SOC) therapy, including off-loading. SOC treatment will include wound cleansing and sharp debridement, fluorescent surveillance of wounds for microbial colonization and the management of infections. Participants observed with greater than 50-percent wound area reduction at the end of 4-weeks will be excluded from entering the Treatment Phase. Those observed with less than 50-percent wound area reduction and who continue to meet the inclusion/exclusion criteria will be allowed to enter the Treatment Phase of the study.
The Treatment Phase (12 weeks) will continue with assessments of the eligibility of the remaining study participants. Thirty study participants (n=30) selected after the four-week Screening Phase will be randomly assigned to either the FAWT or Placebo group of fifteen subjects each (n=15). Study participants and the treating staff members will be blinded to the treatment (FAWT or Placebo) being provided to each participant. During the Treatment Phase subjects will be evaluated every two weeks. These evaluations will include the collection of selected blood chemistries, assessment of ulcer wound healing, wound measurements and microbial surveillance using digital imaging. Paired marginal wound tissue biopsies (3-mm) will be obtained during two points of the Treatment Phase: 1) at the beginning of the Treatment Phase and 2) following the complete closure of the wound or after twelve weeks of Treatment. Study evaluations of the wound will continue until the wound is closed or at twelve weeks, whichever occurs first.
- Conditions
- Diabetic Foot Ulcer
- Being tested
- Folinic acid calcium salt
- Keywords
- Wound Healing, Folic Acid, DNA Methylation
- Medical subject headings
- Diabetic Foot
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Folinic acid calcium saltCombination product
Also called Placebo, PluroGel Burn and Wound Dressing
Folinic acid (2.5%) by combination with Placebo
| Study group | Role | What they receive |
|---|---|---|
| Folic Acid Wound Treatment | Active comparator | Intervention - participants receiving 2.5% folinic acid wound treatment for daily treatment of chronic early stage diabetic foot ulcer wound. This will be applied daily to the study wound selected for monitoring. Receives: Combination Product: Folinic acid calcium salt |
| Placebo | Placebo comparator | Intervention - participants receiving Placebo (PluroGel Burn and Wound Dressing) for daily treatment of chronic early stage diabetic foot ulcer wound. This will be applied daily to the study wound selected for monitoring. Receives: Combination Product: Folinic acid calcium salt |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measures of Wound Closure (actual and percentage)
Reduction of study wound areas
Measured: 12 weeks
Number of Wounds with Complete Healing
Wounds with complete re-epithelialization
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2021
- Study start1 Dec 2021
- Primary completion24 Sep 2024
- Study completion24 Sep 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetic Foot UlcerStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Joseph Boykin, MD
- Sponsor type
- US federal agency
- Collaborators
- George Mason University, Central Arkansas Veterans Healthcare System
- Responsible party
- Sponsor-investigator, Joseph Boykin, MD, Hunter Holmes Mcguire Veteran Affairs Medical Center
- Investigators
- Joseph V Boykin, MD, Principal investigator, Hunter Holmes McGuire VAMC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04723134
- Sponsor's protocol ID
- DFU/FAWT-001(8)
- Status last verified
- Oct 2024
- First submitted
- 20 Jan 2021
- Last updated
- 4 Oct 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Development of a Novel Folic Acid Wound Dressing to Enhance Nitric Oxide Bioactivity Required for Diabetic Foot Ulcer Wound Healing
- ClinicalTrials.gov ID
- NCT04723134
- Acronym / sponsor ID
- DFU/FAWT-001(8)
- Conditions
- Diabetic Foot Ulcer
- Keywords
- Wound Healing, Folic Acid, DNA Methylation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Joseph Boykin, MDUS federal agency
- Collaborators
- George Mason University, Central Arkansas Veterans Healthcare System
- Study start
- 1 Dec 2021 (actual)
- Primary completion
- 24 Sep 2024 (actual)
- Study completion
- 24 Sep 2024 (actual)
- First posted
- 25 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a twelve-week single-center, randomized, double-blind, clinical study to evaluate the safety and efficacy of a folic acid wound treatment (FAWT) versus Placebo in the promotion of healing of chronic, early stage diabetic foot ulcer (ES-DFU) wounds. Male and female Veterans with type-2 diabetes mellitus and chronic ES-DFUs acceptable to the study inclusion/exclusion criteria will be considered for enrollment.
Detailed description
This clinical study is a twelve-week single-center, randomized, double-blind evaluation of the safety and efficacy of a folic acid wound treatment (FAWT) versus Placebo in the promotion of healing of chronic (greater than 4-weeks), early stage diabetic foot ulcer (ES-DFU) wounds (PEDIS-Grade 1 or 2 Depth - wound above fascia without exposed muscle, tendon or bone). Study wound areas will be between 1.0 and 12.0 cm-square.
The chronic, non-healing DFU is a serious and common complication of diabetes. Chronic DFU complications are among the most frequent diabetes-related diagnoses for hospitalization and the leading cause of diabetes-associated lower limb amputations. Increased levels of the tumor suppressor protein p53 in wound keratinocytes from non-healing DFUs suggests increased cell death due to significant (p<0.05) transcription factor activation. Treatment with high dose folic acid (5mg/day) correlates to improved healing in ES-DFU wounds, perhaps by improving folate/methionine metabolism which provides support for DNA repair, the generation of reductive equivalents and regulates DNA methylation, an important epigenetic regulator of p53 transcription activity. Folinic acid calcium salt (calcium folinate) is the bioactive metabolite of folic acid that does not require reduction by dihydrofolate reductase (DHFR). In this study, FAWT (2.5-percent by weight) is provided by compounding 1.25-gms of folinic acid calcium salt with 50-gms of the Placebo (Plurogel Burn and Wound Dressing™, Medline Industries, Inc.). Experimental studies of topical folinic acid demonstrate significant improvements in wound healing parameters with decreased cellular markers of inflammation and increased active signaling of tissue repair. Topical administration of FAWT removes the potential for the adverse impact of high blood folate levels observed with oral high dose folic acid, that could include an increase in the occurrence of sub-classes of colon or prostate cancer.
The study hypothesis is that during a twelve-week evaluation period FAWT may provide significant (p<0.05) improvements, as compared to Placebo, in the rate of healing and complete closure (re-epithelialization) of chronic ES-DFU wounds.
The study will have two phases: Screening and Treatment.
The Screening Phase (first 4 weeks) is designed to determine if male and female Veterans selected as study participants are eligible to proceed to the Treatment Phase of the study. This phase consists of screening assessments that will include evaluation of the rate of study wound closure while the participants receive standard of care (SOC) therapy, including off-loading. SOC treatment will include wound cleansing and sharp debridement, fluorescent surveillance of wounds for microbial colonization and the management of infections. Participants observed with greater than 50-percent wound area reduction at the end of 4-weeks will be excluded from entering the Treatment Phase. Those observed with less than 50-percent wound area reduction and who continue to meet the inclusion/exclusion criteria will be allowed to enter the Treatment Phase of the study.
The Treatment Phase (12 weeks) will continue with assessments of the eligibility of the remaining study participants. Thirty study participants (n=30) selected after the four-week Screening Phase will be randomly assigned to either the FAWT or Placebo group of fifteen subjects each (n=15). Study participants and the treating staff members will be blinded to the treatment (FAWT or Placebo) being provided to each participant. During the Treatment Phase subjects will be evaluated every two weeks. These evaluations will include the collection of selected blood chemistries, assessment of ulcer wound healing, wound measurements and microbial surveillance using digital imaging. Paired marginal wound tissue biopsies (3-mm) will be obtained during two points of the Treatment Phase: 1) at the beginning of the Treatment Phase and 2) following the complete closure of the wound or after twelve weeks of Treatment. Study evaluations of the wound will continue until the wound is closed or at twelve weeks, whichever occurs first.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Folic Acid Wound Treatment | Active comparator | Combination Product: Folinic acid calcium saltIntervention - participants receiving 2.5% folinic acid wound treatment for daily treatment of chronic early stage diabetic foot ulcer wound. This will be applied daily to the study wound selected for monitoring. |
| Placebo | Placebo comparator | Combination Product: Folinic acid calcium saltIntervention - participants receiving Placebo (PluroGel Burn and Wound Dressing) for daily treatment of chronic early stage diabetic foot ulcer wound. This will be applied daily to the study wound selected for monitoring. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Study subjects will be male or female Veterans with T2DM managed with insulin and/or non-insulin therapy who have a chronic, non-healing DFU (wound age: at least 4-weeks) and who have signed an Institutional Review Board approved informed consent document.
- Study subject candidates (SC) - may present with multiple DFUs; however, only one DFU per SC will be selected for study. A DFU-SC must be observed with: 1) at least a four-week history of a non-healing, superficial DFU-wound; PEDIS-Grade 1 or 2 Depth (wound above fascia without exposed muscle, tendon or bone); 2) DFU-wound area between 1-12cm2; 3) DFU-wound with or without clinical neuropathy; 4) DFU-wound lower extremity non-invasive Doppler studies with ankle-brachial index value ≥0.7 and/or Toe pressure ≥50mmHg; and, 5) without evidence of acute infection (e.g., cellulitis, abscess or osteomyelitis) at the time of enrollment.
- If the subject is a woman of childbearing potential she must be practicing an acceptable form of birth control, as determined by the Investigator. All females with an intact uterus must have a negative Beta-Human Chorionic Gonadotropin test (< 5mIU/mL) to proceed with study participation.
Key exclusion criteria (15 listed)
- Any SC who is unable to provide written informed consent will not be enrolled for study participation.
- Any SC who is pregnant or breast feeding, will not be allowed to enroll, or continue, in the study, as pregnancy or breast feeding may impact the study results.
- Subjects with DFU-wounds less than 1cm-square or greater than 12cm-square will be excluded from the study.
- At the beginning of the four-week Screening Phase all SC will be scheduled for study-selected standard DFU wound treatment and off-loading of the study ulcer, as determined by the PI. Subject candidates who are unable to comply with the recommended off-loading of the selected DFU-study wound will be excluded from study.
- During the Screening Phase, any SC whose DFU wound demonstrates more than a fifty-percent (50%) reduction in wound area will be excluded from the study [37].
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 |
|---|---|---|
| Folinic acid calcium saltAlso: Placebo, PluroGel Burn and Wound DressingFolinic acid (2.5%) by combination with Placebo | Combination product | Folic Acid Wound Treatment, Placebo |
Primary outcome
Measures of Wound Closure (actual and percentage)
Time frame: 12 weeks
Reduction of study wound areas
Number of Wounds with Complete Healing
Time frame: 12 weeks
Wounds with complete re-epithelialization
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Oct 2024.
- Individual participant dataSharing planned: No
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Evaluation of Personalized Nutritional Intervention on Wound Healing of Cutaneous Ulcers in Diabetics
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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.
Joseph V Boykin, MD principal investigator
Hunter Holmes McGuire VAMC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Folinic acid calcium salt in people with Diabetic Foot Ulcer, run by Joseph Boykin, MD 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 3 inclusion and 15 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 4 Oct 2024. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Measures of Wound Closure (actual and percentage) (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?
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 4 Oct 2024; AzTrials last refreshed its copy on 8 Nov 2026.