AAT for Soft Tissue Reconstruction

Overseen By Carisa Cooney, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Johns Hopkins University

Must not be taking: Streptomycin, Amphotericin B

Disqualifiers: Autoimmune disease, Diabetes, Infection, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1-2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called Acellular Adipose Tissue (AAT) for repairing soft tissue defects, which are small areas where tissue is missing. AAT uses special material from fat tissue to help restore the shape and function of these areas. The trial aims to assess the safety and effectiveness of AAT injections for individuals with soft tissue defects on their trunk area. Those with a modest soft tissue defect on their trunk and who are willing to follow study guidelines might be a good fit. Participants must be comfortable with procedures like photography and follow-up visits for up to a year. As a Phase 2 trial, this research measures how well the treatment works in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you have conditions like autoimmune connective tissue disease, insulin-dependent diabetes, or are receiving treatment for cancer, you may be excluded from participating.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What prior data suggests that Acellular Adipose Tissue (AAT) is safe for soft tissue reconstruction?

Research has shown that Acellular Adipose Tissue (AAT) is safe for humans. In an earlier study, healthy volunteers who received AAT experienced no serious side effects. Another review found that similar materials made from fat cells, but without the living cells, were both effective and safe for repairing soft tissue.

Animal studies also suggest safety, with no harmful effects observed in either small or large animals. These findings support the idea that AAT is well-tolerated and safe for further testing in individuals requiring soft tissue reconstruction. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for soft tissue defects that often involve surgical grafts or synthetic fillers, Acellular Adipose Tissue (AAT) offers a natural alternative derived from human fat tissue. Researchers are excited about AAT because it provides a minimally invasive option through direct injection, which can potentially improve contour restoration without the need for surgery. Additionally, AAT leverages the natural properties of adipose tissue, aiming for a more seamless integration and long-lasting result.

What evidence suggests that Acellular Adipose Tissue (AAT) might be an effective treatment for soft tissue reconstruction?

Research has shown that Acellular Adipose Tissue (AAT), the treatment under study in this trial, could aid in rebuilding soft tissue. Studies have found that AAT can restore volume and promote tissue regrowth, similar to traditional fat grafting. Animal tests demonstrated AAT's safety, and early human trials confirmed this. A review of various studies also supports AAT as a safe and effective method for regenerating soft tissue. This new material leverages the natural qualities of fat tissue, potentially improving its ability to address soft tissue issues. ^{1 2 3 6 7}

Who Is on the Research Team?

Damon Cooney, MD, PhD

Principal Investigator

The Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine

Are You a Good Fit for This Trial?

This trial is for men and women aged 18-65 with a soft tissue defect on the trunk, who can consent to study requirements, including blood tests and birth control. Excluded are those allergic to certain antibiotics, have low tissue vascularity, immune response to AAT material, active cancer treatment, pregnancy or lactation, poor general health or nutrition.

Inclusion Criteria

Ability to give informed consent

I am a woman who cannot become pregnant due to menopause or surgery.

Willingness to perform follow up visits for 12 months (+/- 30 days)

Exclusion Criteria

Poor nutrition or general medical condition

I do not have a fever above 99º F currently.

Mechanical Trauma

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive permanent injection of Acellular Adipose Tissue (AAT) to restore soft tissue defects

1-2 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of aesthetic appearance and volume retention

6 months

Multiple visits for assessments

Extended Follow-up

Histopathological analysis and additional assessments conducted up to 12 months post-injection

up to 12 months

What Are the Treatments Tested in This Trial?

Interventions

• Acellular Adipose Tissue (AAT)

Trial Overview The trial studies Acellular Adipose Tissue (AAT) for reconstructing soft tissues after injury or trauma. It's a Phase II study that will test different doses of AAT for safety and effectiveness in repairing tissue defects.

How Is the Trial Designed?

Group I: Acellular Adipose Tissue (AAT) Experimental Treatment 1 Intervention

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).

Acellular Adipose Tissue (AAT) is already approved in United States for the following indications:

Approved in United States as Acellular Adipose Tissue (AAT) for:

• Soft tissue reconstruction

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

U.S. Army Medical Research and Development Command

Collaborator

Trials

296

Recruited

249,000+

Armed Forces Institute of Regenerative Medicine

Collaborator

Trials

7

Recruited

220+

Published Research Related to This Trial

Decellularized adipose tissue (DAT) serves as an effective bio-scaffold for tissue engineering, promoting cell attachment and differentiation while being non-immunogenic, making it suitable for various applications like wound healing and breast reconstruction.

DAT retains important growth factors and can recruit host stem cells to form new adipose tissue, demonstrating its potential for soft tissue repair and regeneration in animal models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decellularized Adipose Tissue: Biochemical Composition, in vivo Analysis and Potential Clinical Applications. Mohiuddin, OA., Campbell, B., Poche, JN., et al.[2020]

The adipose-derived extracellular matrix collagen scaffold (ACF) enhances the acellular adipose matrix (AAM) by providing a sustained release of adipokines, which are crucial for promoting the growth of mature adipose tissue.

In experiments with nude mice, the combination of ACF and AAM resulted in the formation of highly vascularized and mature adipose tissue, indicating its potential as an effective strategy for soft-tissue reconstruction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined use of autologous sustained-release scaffold of adipokines and acellular adipose matrix to construct highly vascularized, mature, engineered adipose tissue. Xu, M., He, Y., Li, Y., et al.[2023]

Decellularized adipose matrix is a promising scaffold material for tissue engineering, particularly for regenerating adipose tissue, due to its wide availability and regenerative potential.

Modifying the decellularized adipose matrix allows it to be used beyond adipose tissue, making it applicable in engineering cartilage, bone, neural, and skin tissues, thus expanding its utility in regenerative medicine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Application of Decellularized Adipose Matrix as a Bioscaffold in Different Tissue Engineering. Xiong, C., Yao, W., Tao, R., et al.[2023]

The study successfully created a porous extracellular matrix scaffold from human adipose tissue that retains key components like collagen and laminin, which are important for tissue engineering.

The scaffold demonstrated excellent cellular compatibility, as it supported the proliferation, adhesion, and differentiation of human adipose-derived stem cells, making it a promising candidate for adipose tissue engineering.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Preparation and evaluation of extracellular matrix scaffold of human adipose tissue]. Tian, Y., Liu, Y.[2018]

Decellularized human adipose tissue has been successfully created, containing essential components like collagen and glycoproteins, which can support the growth of stem cells and fat tissue in both small and large animal models.

Phase I safety trials have shown that injecting decellularized adipose tissue scaffolds into human volunteers is safe, with no reported incidents over a period of up to 127 days, highlighting its potential as a biomaterial for tissue engineering.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Developing a clinical grade human adipose decellularized biomaterial. Hayes, DJ., Gimble, JM.[2023]

The combination of fascia matrix and allograft adipose matrix (AAM) significantly improved volume retention and adipose tissue formation, with an 18-week study showing a 2365% increase in adipose area for the 50/50 HA group compared to AAM alone.

This combined bioscaffold also promoted a favorable M1/M2 macrophage ratio, indicating enhanced tissue regeneration and angiogenesis, making it a promising candidate for further research in treating soft tissue defects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combining Allograft Adipose and Fascia Matrix as an Off-the-Shelf Scaffold for Adipose Tissue Engineering Stimulates Angiogenic Responses and Activates a Proregenerative Macrophage Profile in a Rodent Model. Ziegler, ME., Khabaz, K., Khoshab, N., et al.[2023]

The study developed an 'off-the-shelf' acellular adipose tissue (AAT) biomaterial from allograft human tissue, which showed promising results in promoting tissue regeneration and was well tolerated in human subjects, indicating its potential as a safer alternative to traditional fat grafting methods.

In animal models, AAT demonstrated biocompatibility and effective tissue remodeling, especially when combined with human adipose-derived stem cells (ASCs), suggesting that AAT could enhance soft tissue reconstruction outcomes without the complications associated with autologous fat grafts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An immunologically active, adipose-derived extracellular matrix biomaterial for soft tissue reconstruction: concept to clinical trial. Anderson, AE., Wu, I., Parrillo, AJ., et al.[2022]

The study developed an adipose tissue-derived extracellular vesicle (ATEV)-rich hydrogel that significantly enhances both angiogenesis (formation of new blood vessels) and adipogenesis (formation of fat cells) when injected into mice, showing promising results for soft tissue repair.

The optimal concentration of ATEVs for promoting these processes was found to be 50 μg/ml, leading to increased tissue volume and improved tissue characteristics at 4 and 8 weeks post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preparing Adipogenic Hydrogel with Neo-Mechanical Isolated Adipose-Derived Extracellular Vesicles for Adipose Tissue Engineering. Nie, JY., Zhu, YZ., Wang, JW., et al.[2023]

Surgically discarded adipose tissue can be decellularized to create a biomimetic microenvironment that supports the growth of adipose-derived stem cells (ASCs), making it a valuable resource for tissue engineering.

The decellularization process results in a 3D bioscaffold that mimics the natural extracellular matrix, which can be used in various formats for applications like soft tissue regeneration and wound healing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decellularized Adipose Tissue Scaffolds for Soft Tissue Regeneration and Adipose-Derived Stem/Stromal Cell Delivery. Morissette Martin, P., Shridhar, A., Yu, C., et al.[2019]

Acellular adipose matrix (AAM) is a promising option for soft tissue reconstruction due to its high retention rate and ability to promote fat cell formation in the body.

Current decellularization methods can compromise the extracellular matrix properties and leave behind antigens that may cause immune reactions, highlighting the need for improved techniques to enhance AAM safety and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Research Progress on the Immunogenicity and Regeneration of Acellular Adipose Matrix: A Mini Review. Liu, K., He, Y., Lu, F.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39804193/

Acellular Adipose Matrices Seem to Be an Effective and ... Acellular Adipose Matrices Seem to Be an Effective and Safe Strategy for Soft Tissue Regeneration and Volume Restoration: A Systematic Review of ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03544632

NCT03544632 | Acellular Adipose Tissue (AAT) for Soft ... 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 ...

3. link.springer.com link.springer.com/article/10.1007/s00266-024-03924-3

Effect of Injectable Acellular Adipose Matrix on Soft Tissue ... Injectable AAM demonstrates effectiveness comparable to conventional fat grafting concerning volume effects and tissue regeneration in soft tissue ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1742706124005440

Regenerated fat induced by a decellularized adipose ... Decellularized adipose matrix (DAM) is considered to be the most potential biological scaffold for soft tissue repair and reconstruction, ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8760240/

An immunologically active, adipose-derived extracellular ... Soft tissue reconstruction remains an intractable clinical challenge as current surgical options and synthetic implants may produce inadequate outcomes.

6. centerwatch.com centerwatch.com/clinical-trials/listings/NCT03544632/acellular-adipose-tissue-aat-for-soft-tissue-reconstruction

Acellular Adipose Tissue (AAT) for Soft ... Investigators' preclinical data suggest that AAT is safe for use in small and large animals; investigators' clinical (Phase I) data suggest that ...

7. nature.com nature.com/articles/s41536-021-00197-1

An immunologically active, adipose-derived extracellular ... Soft tissue deficits may be surgically reconstructed using autologous adipose tissue, but these procedures can lead to donor site morbidity, ...