Ignite Creation Date:
2024-05-06 @ 3:42 PM
Last Modification Date:
2024-10-26 @ 1:54 PM
Study NCT ID:
NCT04723134
Status:
COMPLETED
Last Update Posted:
2023-06-08
First Post:
2021-01-20
Brief Title:
Evaluation of a Folic Acid Wound Treatment FAWT for Chronic Early-Stage Diabetic Foot Ulcer DFU Healing
Sponsor:
Joseph Boykin MD
Organization:
Hunter Holmes Mcguire Veteran Affairs Medical Center
Study Overview
Official Title:
Development of a Novel Folic Acid Wound Dressing to Enhance Nitric Oxide Bioactivity Required for Diabetic Foot Ulcer Wound Healing
Status:
COMPLETED
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 Male and female Veterans with type-2 diabetes mellitus and chronic ES-DFUs acceptable to the study inclusionexclusion 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 10 and 120 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 p005 transcription factor activation Treatment with high dose folic acid 5mgday correlates to improved healing in ES-DFU wounds perhaps by improving folatemethionine 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 25-percent by weight is provided by compounding 125-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 p005 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 inclusionexclusion 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 n30 selected after the four-week Screening Phase will be randomly assigned to either the FAWT or Placebo group of fifteen subjects each n15 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
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 p005 transcription factor activation Treatment with high dose folic acid 5mgday correlates to improved healing in ES-DFU wounds perhaps by improving folatemethionine 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 25-percent by weight is provided by compounding 125-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 p005 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 inclusionexclusion 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 n30 selected after the four-week Screening Phase will be randomly assigned to either the FAWT or Placebo group of fifteen subjects each n15 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
None