Soft Tissue Injuries, Trauma
Conditions
Keywords
adipose-derived extracellular matrix (ECM), acellular adipose tissue (AAT)
Brief summary
Although other methods (e.g., autologous fat transfer, dermal-/collagen-based fillers) for soft tissue reconstruction exist, each has distinct disadvantages leaving room for improvement in this treatment area. Investigators in the Elisseeff Laboratory (Johns Hopkins University Department of Biomedical Engineering) have recently generated a novel tissue-derived material to create instructive matrices for soft tissue reconstruction called Acellular Adipose Tissue (AAT). This material takes advantage of the inherent bioactivity and unique mechanical properties of subcutaneous adipose tissue. Investigators' preclinical data suggest that AAT is safe for use in small and large animals; investigators' clinical (Phase I) data suggest that AAT is safe for use in humans. These data indicate that a Phase II, dose-escalation study of AAT's safety and efficacy in human subjects is warranted.
Detailed description
Soft tissue volume loss acquired through trauma, congenital malformation or comorbid conditions (i.e., HIV/AIDS) is a common and sometimes devastating problem. Traditional therapies include local tissue transfer, allograft placement, and complex scar revision techniques. Recently, autologous fat transfer has become one of the most commonly employed techniques for improving soft tissue contour deformity particularly for the correction of breast and body defects. While the results from this procedure continue to improve, it requires an additional procedure to harvest fat tissue from the abdomen, thigh or flank leading to donor site morbidity. Clinically, volume loss following autologous fat transfer has been reported to be between 40-60% and usually occurs within the first 4-6 months. Regrafting is often needed and implanted adipose tissue frequently leads to post-operative calcifications. For these reasons, a predictable, "off-the-shelf" material that retains the mechanical and biological properties of adipose tissue would be ideal for the reconstruction of smaller soft tissue defects and soft tissue augmentation. Investigators in the Elisseeff Laboratory (Johns Hopkins University Department of Biomedical Engineering) generated a novel tissue-derived material to create instructive matrices for soft tissue reconstruction \[Acellular Adipose Tissue (AAT)\]. In 2016, investigators conducted a Phase 1, open-label, clinical trial of AAT in healthy volunteers who planned to have elective surgery for the removal of redundant tissue (n=8). Overall, AAT demonstrated satisfactory safety results. No participants experienced serious adverse events (SAEs) or unanticipated adverse events (AEs) related to the study, or exited the study due to AEs. All AEs noted were expected and mild, including redness, bruising, textural changes, hyperpigmentation and tenderness at the injection site. Many other adverse events commonly associated with injections were not observed in any participant throughout the study (i.e., scarring, ulceration, scabbing, purpura, oozing, crusting, blanching, blistering, edema or abrasions). These data indicate that conducting a phase II, dose-escalation, safety and efficacy study in humans is warranted. Based on investigators' experience, investigators hypothesize that AAT will be safe and maintain its volume up to 6 months when injected subcutaneously to restore 5-20cc defects in human soft tissue.
Interventions
Participants (n=15) will be administered between 5cc and 20cc of AAT, depending on their assigned treatment group, via sterile subcutaneous injection into the target defect. The injection is intended to be permanent. After the 3-month study follow-up visit, participants will have the option to undergo additional AAT injection (up to 20cc per treatment) in order to fully correct the defect. Total injected AAT volume per patient will not exceed 40cc. Additional injection is dependent upon study- and patient-specific adverse / unanticipated events to date. Each vial contains a 2 milliliter (mL) dose of the injectable AAT. This volume is similar to other commonly used injectable filler materials intended for soft tissue correction.
Sponsors
Johns Hopkins University
U.S. Army Medical Research and Development Command
Armed Forces Institute of Regenerative Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Men and women aged 18-65 years with at least one modest (5-30cc) soft tissue defect on the trunk and * Willingness to wait up to 6 months to participate in the study (depending on defect size and enrollment-to-date). * Consent to photography for research purposes. * Willingness to follow study requirements. * Ability to give informed consent. * Willingness to perform follow up visits for 12 months (+/- 30 days). * Willingness to undergo complete blood count (CBC) with Differential and Serum Chemistry. For Men and Women of reproductive potential: Willingness to use approved methods of birth control or abstain from sexual intercourse from screening until 6 months post-AAT injection. * Definition of non-childbearing potential for Women: amenorrhea (previous 12 months) or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy). * Definition of non-reproductive potential for Men: confirmed surgically sterile (vasectomy \>3 months prior to screening).
Exclusion criteria
Use of AAT in patients exhibiting autoimmune connective tissue disease is not recommended. When applied properly, AAT has been shown to support the migration of host cells from the surrounding tissue. Therefore, this study will exclude patients with conditions that could inhibit migration of host cells including, but not limited to, the following: * Fever (oral temperature \>99º F at time of screening) * Insulin dependent diabetes * Low vascularity of the tissue intended for elective excision * Local or Systemic Infection * Mechanical Trauma * Poor nutrition or general medical condition * Dehiscence and/or necrosis due to poor revascularization * Specific or nonspecific immune response to some component of the AAT material * Infected or nonvascular surgical sites * Known cancer or receiving treatment for cancer Also: * Pregnant or Lactating females * Inability to cooperate with and/or comprehend post-operative instructions * Inability to speak or read English * Known allergy or sensitivity to Streptomycin or Amphotericin B * Any other reason the study physicians judge would be a contraindication for receiving AAT injections
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AAT efficacy for soft-tissue reconstruction - Volume Retention | 6 months post-final injection | Volume retention documented by pre-to-post injection volumetric changes as detected by 3-dimensional photography |
| AAT efficacy for soft-tissue reconstruction - blinded assessors | 6 months post-final injection | Assessments to determine aesthetic appearance of defects documented by blinded assessors rating defect sites using the Global Aesthetic Improvement Scale (GAIS). 5 point scale ranging from 1 to 5 with 5 = The appearance has worsened compared with the original condition and 1 = Excellent corrective results |
| AAT efficacy for soft-tissue reconstruction - patient-reported | 6 months post-final injection | Post-injection assessment to determine aesthetic outcome documented by patient-reported satisfaction with the repair |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Histopathological analysis of explanted implants | up to 12 months post-injection | Histopathology will be performed on core needle biopsy samples collected at 3, 6, 9, and 12 months post-injection and will be done using the following: H\&E staining to assess (1) native cellular infiltration of the implant, (2) location of implant relative to dermis/subdermis, (3) inflammatory response to implant, and (4) presence of fibrosis |
| Physician Ease of Use Assessments | up to 12 months post-injection | Physician ease of use will be measured through the completion of self-administered surveys by the study surgeon. |
| Participant Comfort Surveys | up to 12 months post-injection | Participant comfort will be measured through the completion of self-administered surveys by the participant. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORDamon Cooney, MD, PhD
The Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine
Outcome results
None listed