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Acellular Adipose Tissue (AAT) for Soft Tissue Reconstruction

Primary Purpose

Soft Tissue Injuries, Trauma

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Acellular Adipose Tissue (AAT)
Sponsored by
Johns Hopkins University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Soft Tissue Injuries focused on measuring adipose-derived extracellular matrix (ECM), acellular adipose tissue (AAT)

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Johns Hopkins University School of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Acellular Adipose Tissue (AAT)

Arm Description

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).

Outcomes

Primary Outcome Measures

AAT efficacy for soft-tissue reconstruction in humans to restore volume in soft tissue defects of the trunk
Volume retention documented by pre-to-post injection volumetric changes as detected by 3-dimensional photography
AAT efficacy for soft-tissue reconstruction in humans to restore volume in soft tissue defects of the trunk
Assessments to determine aesthetic appearance of defects documented by blinded assessors rating defect sites using the Global Aesthetic Improvement Scale (GAIS)
AAT efficacy for soft-tissue reconstruction in humans to restore volume in soft tissue defects of the trunk
Post-injection assessment to determine aesthetic outcome documented by patient-reported satisfaction with the repair

Secondary Outcome Measures

Histopathological analysis of explanted implants
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
Physician ease of use will be measured through the completion of self-administered surveys by the study surgeon.
Participant Comfort Surveys
Participant comfort will be measured through the completion of self-administered surveys by the participant.

Full Information

First Posted
April 25, 2018
Last Updated
February 7, 2023
Sponsor
Johns Hopkins University
Collaborators
U.S. Army Medical Research and Development Command, Armed Forces Institute of Regenerative Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT03544632
Brief Title
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

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 21, 2018 (Actual)
Primary Completion Date
February 28, 2025 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Johns Hopkins University
Collaborators
U.S. Army Medical Research and Development Command, Armed Forces Institute of Regenerative Medicine

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Soft Tissue Injuries, Trauma
Keywords
adipose-derived extracellular matrix (ECM), acellular adipose tissue (AAT)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Acellular Adipose Tissue (AAT)
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Acellular Adipose Tissue (AAT)
Intervention Description
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 Measure Information:
Title
AAT efficacy for soft-tissue reconstruction in humans to restore volume in soft tissue defects of the trunk
Description
Volume retention documented by pre-to-post injection volumetric changes as detected by 3-dimensional photography
Time Frame
6 months post-final injection
Title
AAT efficacy for soft-tissue reconstruction in humans to restore volume in soft tissue defects of the trunk
Description
Assessments to determine aesthetic appearance of defects documented by blinded assessors rating defect sites using the Global Aesthetic Improvement Scale (GAIS)
Time Frame
6 months post-final injection
Title
AAT efficacy for soft-tissue reconstruction in humans to restore volume in soft tissue defects of the trunk
Description
Post-injection assessment to determine aesthetic outcome documented by patient-reported satisfaction with the repair
Time Frame
6 months post-final injection
Secondary Outcome Measure Information:
Title
Histopathological analysis of explanted implants
Description
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
Time Frame
up to 12 months post-injection
Title
Physician Ease of Use Assessments
Description
Physician ease of use will be measured through the completion of self-administered surveys by the study surgeon.
Time Frame
up to 12 months post-injection
Title
Participant Comfort Surveys
Description
Participant comfort will be measured through the completion of self-administered surveys by the participant.
Time Frame
up to 12 months post-injection

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Damon Cooney, MD, PhD
Organizational Affiliation
The Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Johns Hopkins University School of Medicine
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
19083543
Citation
Bucky LP, Percec I. The science of autologous fat grafting: views on current and future approaches to neoadipogenesis. Aesthet Surg J. 2008 May-Jun;28(3):313-21; quiz 322-4. doi: 10.1016/j.asj.2008.02.004.
Results Reference
background
PubMed Identifier
19305242
Citation
Wan DC, Lim AT, Longaker MT. Craniofacial autologous fat transfer. J Craniofac Surg. 2009 Mar;20(2):273-4. doi: 10.1097/SCS.0b013e31819921d3. No abstract available.
Results Reference
background
PubMed Identifier
18843123
Citation
Cordeiro PG. Breast reconstruction after surgery for breast cancer. N Engl J Med. 2008 Oct 9;359(15):1590-601. doi: 10.1056/NEJMct0802899. No abstract available.
Results Reference
background
PubMed Identifier
20217253
Citation
Rosson GD, Magarakis M, Shridharani SM, Stapleton SM, Jacobs LK, Manahan MA, Flores JI. A review of the surgical management of breast cancer: plastic reconstructive techniques and timing implications. Ann Surg Oncol. 2010 Jul;17(7):1890-900. doi: 10.1245/s10434-010-0913-7. Epub 2010 Mar 9.
Results Reference
background
PubMed Identifier
16409589
Citation
Pulagam SR, Poulton T, Mamounas EP. Long-term clinical and radiologic results with autologous fat transplantation for breast augmentation: case reports and review of the literature. Breast J. 2006 Jan-Feb;12(1):63-5. doi: 10.1111/j.1075-122X.2006.00188.x.
Results Reference
background
PubMed Identifier
19280638
Citation
Cheng MH, Uriel S, Moya ML, Francis-Sedlak M, Wang R, Huang JJ, Chang SY, Brey EM. Dermis-derived hydrogels support adipogenesis in vivo. J Biomed Mater Res A. 2010 Mar 1;92(3):852-8. doi: 10.1002/jbm.a.32410.
Results Reference
background
PubMed Identifier
18571717
Citation
Uriel S, Huang JJ, Moya ML, Francis ME, Wang R, Chang SY, Cheng MH, Brey EM. The role of adipose protein derived hydrogels in adipogenesis. Biomaterials. 2008 Sep;29(27):3712-3719. doi: 10.1016/j.biomaterials.2008.05.028. Epub 2008 Jun 24.
Results Reference
background
PubMed Identifier
22327888
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.
Results Reference
background
Links:
URL
https://clinicaltrials.gov/ct2/show/NCT02817984
Description
Safety Study of Acellular Adipose Tissue for Soft Tissue Reconstruction

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Acellular Adipose Tissue (AAT) for Soft Tissue Reconstruction

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