Reducing Side-effects of Autologous Skin Tissue Harvesting

• ClinicalTrials.gov Identifier: NCT02234193
• Recruitment Status: Completed
• First Posted: September 9, 2014
• Last Update Posted: January 14, 2021
• Sponsor: Massachusetts General Hospital
• Information provided by (Responsible Party): Richard Rox Anderson, MD, Massachusetts General Hospital

Tracking Information

• First Submitted Date: August 27, 2014
• First Posted Date: September 9, 2014
• Last Update Posted Date: January 14, 2021
• Actual Study Start Date: June 2016
• Actual Primary Completion Date: March 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 4, 2014)

Evaluation of Efficacy - Change from baseline scarring at 8 weeks [ Time Frame: 24 h, 1 week, 2 weeks, 4 weeks and 8 weeks post treatment ]

The extent of scarring caused by the harvesting of micro-skin columns will be assessed by investigators and patients using the Patient and Observer Scar Assessment Scale (POSAS) at all of the follow-up time points. Patient and Observer Scar Assessment Scale (POSAS)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 4, 2014)

• Assessing Subject Side-effects - Change from baseline side-effects at 8 weeks [ Time Frame: day 0, 24 h, 1 week, 2 weeks, 4 weeks and 8 weeks after the procedure ]
  A Major side effect is defined as an intolerable side effect that would warrant the cessation of treatment because of a risk to the subject's health or because the subject could not tolerate the treatment due to a subjective personal measure (e.g. severe pain). A Minor side effect is a side effect that while uncomfortable would not threaten the subject's health or cause the cessation of treatment due to lack of comfort. Major side effects include: severe pain (Pain ≥ 8/10 on VAS scale), severe blistering (with potential for secondary infection) and ulceration with scarring. Subjects will be asked for each site to fill in the following sentence: "The side effects I experienced with micro biopsies were: "0: Did not have this side effect / 1: Mild / 2: Moderate / 3: Severe Swelling, Redness, Scabs, Pus or pus blisters, Scaling, Itchy skin, Erosion, Tanning, Lightening of the skin, Minor blistering, Wheals, Bleeding, Folliculitis, Oozing, Numbness
• Pain assessment - Visual Analog Scale (VAS) - Change from baseline pain at 8 weeks [ Time Frame: DAY 0, 24h, 1, 2, 4 & 8 weeks ]
  The VAS will be completed by study subject at baseline and at each follow-up visit for each test site. Pain is any of the following: sensation of tingling, stinging, prickling, or burning feeling, heat under the skin, tenderness, mild, moderate or severe pain). Specific VAS form is attached Subjects will be asked to circle the number below that most closely corresponds to pain associated with each treatment site. 0 1 2 3 4 5 6 7 8 9 10 (NO PAIN WORST PAIN)

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: September 4, 2014)

• Histopathology examination [ Time Frame: 8 weeks ]
  After the subject's elective abdominoplasty procedure, the excised skin will be collected. Samples will be taken from the excised skin in areas where micro skin biopsies were harvested at time 0 (visit 2). Since all tissue samples are collected from skin that has already been excised during abdominoplasty surgery, the collection of samples for histopathology poses no additional risk for the subjects.
• Subject Satisfaction Survey - Change from baseline side-effects at 8 weeks [ Time Frame: Day 0, 24h, 1, 2, 4 & 8 Weeks ]
  In this survey, subjects are given a list of the side effects of the micro-biopsies before treatment (Visits1-7) and are asked to rate each question on a scale of 1 to 5. After treatment, they are given this specific survey (but specific to each treatment site) after each month of treatment as a repeated measure of side effects, before and after each procedure. They will be asked the question based on the treatment site name, if they consider the treatment cosmetically acceptable. For example: Answer the questions bellow with a number: 5 Agree Strongly 4 Agree 3 Neutral 2 Disagree 1 Disagree Strongly The treatment performed on the SITE 1 (same for other sites SITES) SITE 1 treatment is safe SITE 1 treatment is cosmetically sound (Do you think it looks ok?). The side effects of SITE 1 treatment are tolerable.

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Reducing Side-effects of Autologous Skin Tissue Harvesting
• Official Title: A Pilot Clinical Trial to Reduce Side-effects of Autologous Skin Tissue Harvesting

Brief Summary

The investigators are doing this research study to learn about how the skin heals after many microscopic skin biopsies are collected.

Skin-grafting is a life-saving procedure for people with large area skin wounds caused by burns or trauma. Conventional autologous (self) skin grafting techniques require the creation of large donor site wounds, causing numerous complications including pain, infection, blistering, discoloration, and scarring. Based on previous research, many of these adverse effects can be improved, or even eliminated, by harvesting skin tissue in very small biopsies. These "micro-biopsies" are less than the size of a sewing pin. Then, they are put back together into a skin graft.

This concept is based on clinical observations from fractional photothermolysis laser therapy, an FDA approved laser that has been previously developed by the investigators research group for the treatment of scars and ageing skin. With this laser technique, thousands to millions of small burns are produced by laser on a patient's skin, and the skin responds by healing the damaged areas to create new healthy skin within days and without scarring.

Although the results of laser treatment are well-known, it is not known what happens when we harvest the skin using needles instead of using the laser to cut the skin. The investigators also would like to understand how the body heals the skin. Understanding how this works helps in understanding wound healing, and may lead to future treatments for healing large wounds, disfiguring burn scars, and preventing scar formation.

A tummy tuck (abdominoplasty surgery) is done to remove excessive skin of the belly. This is an elective surgery, in other words, it is optional and usually done for cosmetics reasons (to improve the appearance).

The skin of the belly that is removed during an abdominoplasty surgery (tummy tuck) is discarded. The skin of the area removed is called "pre-abdominoplasty skin". The investigators would like to study the effects of the micro-biopsies on pre-abdominoplasty skin to exam how the skin heals over time and to study the skin that will be removed during the abdominoplasty surgery.

This is a pilot study. Pilot studies are done on a small group of subjects to learn if a larger study would be useful.

The investigators are asking subjects to take part in this study who are healthy with an abdominoplasty surgery (tummy tuck) scheduled at Massachusetts General Hospital (MGH) by a plastic surgeon .

The investigators will enroll about 28 subjects in this research study, all at MGH.

The Department of Defense is paying for this study to be done.

• Detailed Description: It will take you about 8 weeks to complete this research study. During this time, the investigators will ask you to make up to 7 study visits to MGH.
• Study Type: Interventional
• Study Phase: Early Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Scar

Intervention

• Device: Micro biopsy
  This is a prospective, self-controlled study of the healing response after collecting micro skin biopsies of different sizes (from 200 µm to 2 mm in diameter) from up to seven 1.5 x 1.5 cm biopsy sites in pre-abdominoplasty skin areas that are scheduled for surgical removal. The collection procedure will be performed using similar techniques as standard skin biopsies: the skin area involved will be cleaned with alcohol pads, and 1% buffered lidocaine with epinephrine anesthesia will be administered locally, then micro biopsies of skin will be removed by biopsy punch/harvesting needle. No more than 10% of the skin area within each biopsy site will be collected. Tattoo ink as described will be applied to 4 micro-biopsies at the corners of each biopsy test site
• Procedure: Lidocaine with epinephrine
  The skin area involved will be cleaned with alcohol pads, and 1% buffered lidocaine with epinephrine anesthesia will be administered locally, prior to the surgical procedure
  Other Name: Lidocaine

Study Arms

• Active Comparator: Micro biopsies 2mm x control
  2 mm diameter micro biopsies will be performed on all subjects.
  Interventions:

  • Device: Micro biopsy
  • Procedure: Lidocaine with epinephrine
• Active Comparator: Micro biopsies 1mm x control
  1 mm diameter micro biopsies will be performed on all subjects.
  Interventions:

  • Device: Micro biopsy
  • Procedure: Lidocaine with epinephrine
• Active Comparator: Micro biopsies 0.8 mm x control
  0.8 mm diameter micro biopsies will be performed on all subjects.
  Interventions:

  • Device: Micro biopsy
  • Procedure: Lidocaine with epinephrine
• Active Comparator: Micro biopsies 0.6 mm x control
  0.6 mm diameter micro biopsies will be performed on all subjects.
  Interventions:

  • Device: Micro biopsy
  • Procedure: Lidocaine with epinephrine
• Active Comparator: Micro biopsies 0.5 mm x control
  0.5 mm diameter micro biopsies will be performed on all subjects.
  Interventions:

  • Device: Micro biopsy
  • Procedure: Lidocaine with epinephrine
• Active Comparator: Micro biopsies 0.40 mm x control
  0.4 mm diameter micro biopsies will be performed on all subjects.
  Interventions:

  • Device: Micro biopsy
  • Procedure: Lidocaine with epinephrine
• Active Comparator: Micro biopsies 0.20 mm x control
  0.2 mm diameter micro biopsies will be performed on all subjects.
  Interventions:

  • Device: Micro biopsy
  • Procedure: Lidocaine with epinephrine

• Publications *: Rasmussen CA, Tam J, Steiglitz BM, Bauer RL, Peters NR, Wang Y, Anderson RR, Allen-Hoffmann BL. Chimeric autologous/allogeneic constructs for skin regeneration. Mil Med. 2014 Aug;179(8 Suppl):71-8. doi: 10.7205/MILMED-D-13-00480.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 12, 2021): 8
• Original Estimated Enrollment (submitted: September 4, 2014): 28
• Actual Study Completion Date: March 2019
• Actual Primary Completion Date: March 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Healthy adults (>18 years old) scheduled to undergo elective abdominoplasty surgery at MGH, male or female.
2. Willingness to participate in the study
3. Willingness to undergo biopsies of full-thickness skin tissue from the pre-abdominoplasty skin, and have the biopsy sites marked by tattoos.
4. Informed consent agreement signed by the subject
5. Willingness to follow the treatment and follow-up schedules, and post treatment care requirements
6. Willingness to not use topical or systemic (oral) anti-scarring or anti-inflammatory* medications during the study period.

Exclusion Criteria:

1. Subjects who are immunocompromised or immunosuppressed*
2. Subject is unable to comply with treatment, home care or follow-up visits
3. Subject has an infection or other dermatologic condition in the area to be treated
4. Subjects with a personal or family history of keloid formation.
5. Subjects with pre-existing scars, tattoos, birthmarks, or other physical features in the area to be treated, such that the experimental outcome may be confounded.
6. Subjects with a history of coagulopathy, or are taking anticoagulants
7. Subjects taking daily oral aspirin.
8. Subject is currently enrolled in a clinical study of any other unapproved investigational drug or device.
9. Subjects with any contraindications for elective abdominoplasty, as determined by their treating plastic surgeon and/or pre-op anesthesiologist.
10. Subjects with current drug or alcohol addiction.
11. Subjects who are pregnant and/or breastfeeding
12. Subjects with tape adhesive allergies
13. Subjects with known allergies to injectable lidocaine or other topical anesthetics
14. Subjects with uncontrolled or unstable chronic disease such as diabetes, hepatitis, hypertension, etc.
15. Subjects taking oral corticosteroids or topical steroids on the study area.
16. Subjects using prescription or over-the-counter medication or cosmetics containing: retinoids, glycolic acid, salicylic acid or any other remedies that might affect the healing process. (Non-medicated moisturizers are ok).
17. Subjects enrolled in other clinical studies taking any unknown or not-FDA approved medications.
18. Any other condition or laboratory value that would, in the professional opinion of the investigator, potentially affect the subject's response or the integrity of the data or would pose an unacceptable risk to the subject.

Notes:

*About Anti-Inflammatory Medication and Immune Status The inflammatory response associated with tissue wounding is known to have substantial effects on the process of scarring, therefore all subjects who are immunocompromised, or undergoing anti-inflammatory/immunosuppressive therapies will be excluded from the study. All new medication should be reported to study doctor before each visit.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 50 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02234193
• Other Study ID Numbers: 2014P000120
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes

• Responsible Party: Richard Rox Anderson, MD, Massachusetts General Hospital
• Study Sponsor: Massachusetts General Hospital
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Massachusetts General Hospital
• Verification Date: January 2021