Wound Heal, Wound of Skin
Conditions
Keywords
collagen powder, punch biopsy wound
Brief summary
We have designed a pilot study to investigate the effect and potential utility of topical NuvagenTM (collagen powder) on the rate and quality of wound healing in healthy volunteers using the punch biopsy method. After inducing an acute full-thickness wound, the rate of complete healing of a wound treated with topical NuvagenTM (collagen powder) will be compared to the rate of complete healing of a wound treated with primary closure with sutures, the current gold standard. Qualification and semi-quantification of histologic and immunohistochemical markers will be used to assess the maturity and structural stability of the wound bed. Positive findings would suggest that NuvagenTM (collagen powder) may be capable of stimulating the healing of acute wounds in a similar or even superior manner to primary closure, suggesting collagen powder may be used in place of sutures, and encouraging further studies to characterize its therapeutic potential in dermatologic surgery.
Detailed description
Each patient received a single 4mm punch biopsy on each anterior thigh to provide for internalized controls. One wound was managed with PC, while the other was treated with daily topical collagen powder for up to four weeks. Prior to each biopsy, the areas were cleansed with an alcohol swab and anesthetized using 1 mL of 2% lidocaine with epinephrine. An Integra Miltex 4.0 mm Standard Biopsy Punch instrument was used to create full-thickness wounds and pressure was applied with gauze until hemostasis occurred. Up to one gram of topical type 1, 100% bovine collagen powder (NuvagenTM, CPN Biosciences, Inc., Largo, FL) was placed on one wound before covering it with a non-adherent sterile dressing. The other wound underwent PC with two epidermal sutures (Ethilon Nylon Sutures, Ethicon, Somerville, NJ) and was similarly covered with a sterile dressing. At the four week follow-up, wounds were re-biopsied following the same procedures. For home treatment, patients were provided with collagen powder in one-gram containers and dressings along with the following instructions: 1) Irrigate the wound with tap water or saline solution, 2) Dry the wound with gently with dry gauze, 3) Apply up to one gram of collagen powder to the wound, and 4) Apply a sterile dressing. Assistance from a caregiver was permitted as needed. This procedure was repeated daily for four weeks after the first biopsy and until wound closure after the second biopsy. For wounds closed primarily, patients were instructed to apply petroleum jelly before covering the wounds with sterile dressings.
Interventions
DEVICENuvagen Collagen Powder
Daily application of Nuvagen collagen powder for 2 to 4 weeks following wounding
Sponsors
CPN Biosciences
Adam Friedman
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a self-controlled trial in which subjects will receive punch biopsies at sites on each leg, and will receive a different treatment on each of the 2 sites.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Outpatient, male or female subjects of any race, 18-75 years of age * Able to understand the requirements of the study and understand and sign Informed Consent/HIPAA Authorization forms * Patients willing to refrain from using topical medications to punch biopsy sites * Patients who are willing to follow protocol instructions and return for follow-up visits
Exclusion criteria
* Patients that have any medical or skin condition that could impair wound healing * Patients that have used systemic medications that suppress the immune system within 5 half-lives (if known), or 2 months of enrollment (i.e. corticosteroids) * Patients that have applied topical steroids to the thigh(s) in the 2 weeks prior to enrollment * Patients that are currently participating in an investigational study of a drug or device or have participated within 4 weeks of enrollment * Patients that in the opinion of the investigator demonstrate evidence of unwillingness or inability to follow instructions or to complete the study * Patients currently using systemic antimicrobials * Patients with a history of diabetes mellitus * Patients with a history of bleeding disorders or concomitant treatment with aspirin or anticoagulants (including heparin, low molecular weight heparin, warfarin, fondaparinux, or rivaroxaban) * Patients with a history of keloids or hypertrophic scars * Patients with other conditions considered by the investigator to be reasons for disqualification that may jeopardize subject safety or interfere with the objectives of the trial (e.g., acute illness or exacerbation of chronic illness) * Patients with a known allergy or sensitivity to any component of the test medication (including bovine and/or collagen products) or local anesthetic agent used * Current or previous users of tobacco products * Recent alcohol or drug abuse is evident * Pregnant females or nursing mothers. Eligible women of reproductive age will be required to have a negative urine pregnancy test at screening. They will also be required to be on at least 1 reliable form of effective birth control \[examples: barrier method (condoms, diaphragm), oral, injectable, implant birth control or abstinence\] during the course of this study and 30 days following the last treatment period.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Wound Diameter | 4 weeks after first biopsy | Change in wound diameter will be assessed digitally from photographs of the wounds obtained at several distinct time points, both at the time of wounding and afterwards. The diameter of the biopsy wound is measured to reflect a change from baseline in wound size day 0 and again at week 4. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Collagen Staining in Histopathology | at 4 weeks after first biopsy | histopathological processing was performed by HistoWiz, Inc. (Brooklyn, NY) on one baseline sample and both four-week samples, including hematoxylin and eosin (H&E), CD31 (platelet-derived endothelial cell adhesion molecule-1), and Masson trichrome staining. H&E staining was used to examine the quality of the epidermis and colla- gen bundles as well as to observe the amount of inflammatory granulation tissue. |
Countries
United States
Participant flow
Recruitment details
Eight healthy volunteers 18 to 75 years old were enrolled after Informed consent form was signed for this study
Pre-assignment details
Healthy patients 18 -75 years included. Patients with impaired wound healing, systemic immunosuppressants use within 2 months, steroid application to the thighs 2 weeks, participation in investigational trials in less than 4weeks , systemic antibiotics use , History of Diabetes Mellitus, bleeding disorders, keloids, hypertrophic scarring, allergy to collagen powders, current or past history of tobacco, alcohol or other illicit drug us and pregnant or nursing females were excluded.
Participants by arm
| Arm | Count |
|---|---|
| All Participants Biopsy of one anterior thigh of all patients followed by wound care with Primary Closure. Biopsy of other anterior thigh in all patients followed by wound care with Collagen powder | 8 |
| Total | 8 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 37 years |
| Fitz-Patrick Skin type Type I | 1 Participants |
| Fitz-Patrick Skin type Type II | 3 Participants |
| Fitz-Patrick Skin type Type III | 1 Participants |
| Fitz-Patrick Skin type Type III-IV | 2 Participants |
| Fitz-Patrick Skin type Type IV | 0 Participants |
| Fitz-Patrick Skin type Type V | 1 Participants |
| Fitz-Patrick Skin type Type VI | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Region of Enrollment United States | 8 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 0 / 8 | 0 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 |
Outcome results
Primary
Change in Wound Diameter
Change in wound diameter will be assessed digitally from photographs of the wounds obtained at several distinct time points, both at the time of wounding and afterwards. The diameter of the biopsy wound is measured to reflect a change from baseline in wound size day 0 and again at week 4.
Time frame: 4 weeks after first biopsy
Population: 8 voluntary out patients were selected between ages 18 and 75, 2 female subjects. There was one patient with Fitzpatrick Skin type (FST) I, Three were FST II, one FST III, tow, FST III/IV, and one FST V.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Primary Closure | Change in Wound Diameter | 95.94 Centimeters |
| Collagen Powder | Change in Wound Diameter | 95.94 Centimeters |
Other Pre-specified
Collagen Staining in Histopathology
histopathological processing was performed by HistoWiz, Inc. (Brooklyn, NY) on one baseline sample and both four-week samples, including hematoxylin and eosin (H&E), CD31 (platelet-derived endothelial cell adhesion molecule-1), and Masson trichrome staining. H&E staining was used to examine the quality of the epidermis and colla- gen bundles as well as to observe the amount of inflammatory granulation tissue.
Time frame: at 4 weeks after first biopsy
Population: 8 voluntary out patients were selected between ages 18 and 75, 2 female subjects. There was one patient with Fitzpatrick Skin type (FST) I, Three were FST II, one FST III, tow, FST III/IV, and one FST V.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Primary Closure | Collagen Staining in Histopathology | 125.8 percentage of Masson trichrome staining |
| Collagen Powder | Collagen Staining in Histopathology | 173.40 percentage of Masson trichrome staining |