Topical Collagen Powder for Healing of Acute Full-thickness Wounds

Topical Collagen Powder as a Wound Healing Adjuvant for Acute Full-thickness Punch Biopsy-induced Human Wounds: a Pilot Study

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.

Study Overview

• Status: Completed
• Conditions: Wound Heal; Wound of Skin
• Intervention / Treatment: Device: Nuvagen Collagen Powder

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.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • George Washington Medical Faculty Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Internalized Control; Subjects will receive 2 punch biopsy created wounds, one on each thigh, which will be addressed with primary closure with sutures or will be treated with Nuvagen collagen powder at time of wounding and daily thereafter. Suture(s) will be removed in 2 weeks. At week four, the wounded site will be biopsied again for tissue collection/evaluation, and treated with primary closure again. Suture(s) will be removed within to weeks. For those using collagen powder, the biopsy site will be biopsied again at week 4, and wound care will again be with NuvagenTM collagen powder until closure.

Device: Nuvagen Collagen Powder; Daily application of Nuvagen collagen powder for 2 to 4 weeks following wounding

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	4 weeks after first biopsy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Patient Overall Assessment Scale and responses to assess wound healing improvement.	Patients will assess the change in overall improvement of their wounds using a 4-point scale, where 1 = excellent improvement, 2 = good / moderate improvement, 3 = no change, 4 = worsening. Improvement will be indicated by a decrease by ≥ 1 point compared to the previous assessment. Worsening will be indicated by an increase in this scale by ≥ 1 point compared to the previous assessment. Patients will also be asked preference between the collagen powder and primary closure.	Patient Overall Assessment Scale scores and responses will be obtained at weeks 1, 2, 4, 6, and 12.
Change in Pruritus Numerical Rating Scale to assess patient itch symptoms.	Patients will also score change in itch symptoms on the Pruritus Numerical Rating Scale, which ranges from 0-10, where 0 = no itch and 10 = worst itch imaginable. Improvement will be indicated by a decrease by ≥ 2 points compared to the previous assessment. Worsening will be indicated by an increase in this scale by ≥ 2 points compared to the previous assessment.	Pruritus Numerical Rating Scale scores will be obtained at weeks 1, 2, 4, 6, and 12.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	at 4 weeks after first biopsy

Collaborators and Investigators

• Sponsor: Adam Friedman
• Collaborators: CPN Biosciences
• Investigators: Principal Investigator: Adam Friedman, MD, GW School of Medicine and Health Sciences

Publications and helpful links

General Publications

• Qureshi A, Murphy E, Milando R, Rengifo-Pardo M, Clayton C, Friedman A. A Head-to-Head Comparison of Topical Collagen Powder to Primary Closure for Acute Full-Thickness Punch Biopsy-Induced Human Wounds: An Internally Controlled Pilot Study. J Drugs Dermatol. 2019 Jul 1;18(7):667-673.

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2018
• Primary Completion (Actual): October 18, 2018
• Study Completion (Actual): November 1, 2018

Study Registration Dates

• First Submitted: March 15, 2018
• First Submitted That Met QC Criteria: March 22, 2018
• First Posted (Actual): March 29, 2018

Study Record Updates

• Last Update Posted (Actual): March 28, 2023
• Last Update Submitted That Met QC Criteria: March 27, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: collagen powder; punch biopsy wound
• Additional Relevant MeSH Terms: Wounds and Injuries
• Other Study ID Numbers: 26552436

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The results are published in Journal of Dermatology and Drugs
• IPD Sharing Time Frame: The data will be available for public reference after JAN 29 2018
• IPD Sharing Access Criteria: Journal of Dermatology and Drugs online access
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes