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Acellular Adipose Tissue (AAT) for Soft Tissue Reconstruction

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ClinicalTrials.gov Identifier: NCT03544632
Recruitment Status : Recruiting
First Posted : June 4, 2018
Last Update Posted : July 12, 2018
Sponsor:
Collaborators:
U.S. Army Medical Research and Materiel Command
Armed Forces Institute of Regenerative Medicine
Information provided by (Responsible Party):
Johns Hopkins University

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.

Condition or disease Intervention/treatment Phase
Soft Tissue Injuries Trauma Drug: Acellular Adipose Tissue (AAT) Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 21, 2018
Estimated Primary Completion Date : December 7, 2019
Estimated Study Completion Date : June 7, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Acellular Adipose Tissue (AAT)
This open-label, phase II, dose-escalation study will be conducted in human subjects seeking repair of modest (approx. 5-30cc) soft tissue defects of the trunk (n=15). All participants will be treated via permanent injection of the study intervention (AAT injection) to restore the defect's contour. All study data will be collected in Case Report Forms (CRFs) and entered into a customized study database, created and maintained in HIPAA-compliant Research Electronic Data Capture (REDCap) software (14).
Drug: Acellular Adipose Tissue (AAT)

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.





Primary Outcome Measures :
  1. AAT efficacy for soft-tissue reconstruction in humans to restore volume in soft tissue defects of the trunk [ Time Frame: 6 months post-final injection ]
    Volume retention documented by pre-to-post injection volumetric changes as detected by 3-dimensional photography

  2. AAT efficacy for soft-tissue reconstruction in humans to restore volume in soft tissue defects of the trunk [ Time Frame: 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)

  3. AAT efficacy for soft-tissue reconstruction in humans to restore volume in soft tissue defects of the trunk [ Time Frame: 6 months post-final injection ]
    Post-injection assessment to determine aesthetic outcome documented by patient-reported satisfaction with the repair


Secondary Outcome Measures :
  1. Histopathological analysis of explanted implants [ Time Frame: 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

  2. Physician Ease of Use Assessments [ Time Frame: up to 12 months post-injection ]
    Physician ease of use will be measured through the completion of self-administered surveys by the study surgeon.

  3. Participant Comfort Surveys [ Time Frame: up to 12 months post-injection ]
    Participant comfort will be measured through the completion of self-administered surveys by the participant.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03544632


Contacts
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Contact: Carisa Cooney, MPH 443-287-4629 ccooney3@jhmi.edu

Locations
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United States, Maryland
Johns Hopkins University School of Medicine Recruiting
Baltimore, Maryland, United States, 21287
Contact: Carisa M Cooney, MPH    443-287-4629    ccooney3@jhmi.edu   
Contact: Jordan Garcia, MD       jordan_garcia@jhmi.edu   
Sponsors and Collaborators
Johns Hopkins University
U.S. Army Medical Research and Materiel Command
Armed Forces Institute of Regenerative Medicine
Investigators
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Principal Investigator: Damon Cooney, MD, PhD The Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine

Additional Information:
Publications:

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Responsible Party: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT03544632     History of Changes
Other Study ID Numbers: IRB00155003
First Posted: June 4, 2018    Key Record Dates
Last Update Posted: July 12, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Johns Hopkins University:
adipose-derived extracellular matrix (ECM)
acellular adipose tissue (AAT)

Additional relevant MeSH terms:
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Soft Tissue Injuries
Wounds and Injuries