Clinical trial NCT03544632: Acellular Adipose Tissue (AAT) for Soft Tissue Reconstruction
Official title: A Phase II, Dose-escalation, Open-label Study Evaluating the Safety and Efficacy of Permanently-placed Acellular Adipose Tissue (AAT) in Human Subjects With Modest Soft Tissue Defects of the Trunk
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Soft Tissue Injuries
Trauma
Keywords: adipose-derived extracellular matrix (ECM)
acellular adipose tissue (AAT)
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: U.S. Army Medical Research and Development Command
name: Armed Forces Institute of Regenerative Medicine
First posted: 2018-06-04
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: AAT efficacy for soft-tissue reconstruction - Volume Retention
timeFrame: 6 months post-final injection
measure: AAT efficacy for soft-tissue reconstruction - blinded assessors
timeFrame: 6 months post-final injection
measure: AAT efficacy for soft-tissue reconstruction - patient-reported
timeFrame: 6 months post-final injection
Secondary outcomes:
measure: Histopathological analysis of explanted implants
timeFrame: up to 12 months post-injection
measure: Physician Ease of Use Assessments
timeFrame: up to 12 months post-injection
measure: Participant Comfort Surveys
timeFrame: up to 12 months post-injection
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
Study officials:
affiliation: The Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine
name: Damon Cooney, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Wu I, Nahas Z, Kimmerling KA, Rosson GD, Elisseeff JH. An injectable adipose matrix for soft-tissue reconstruction. Plast Reconstr Surg. 2012 Jun;129(6):1247-1257. doi: 10.1097/PRS.0b013e31824ec3dc.