Fibroblast Injection for Amputee Limb Care

Overseen By Luis Garza, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Major Extremity Trauma Research Consortium

Must not be taking: Immunosuppressants, Steroids, Methemoglobinemia drugs

Disqualifiers: Pregnancy, Autoimmune conditions, Active smoker, 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: 5

Duration: 1 week

20 Participants Needed

Trial Summary

What is the purpose of this trial?

The study will enroll 20 adults ages 18-75 with a transtibial amputation with mature residual limbs who are ambulatory prosthesis users. Participants will be randomized to either treatment with low dose volar fibroblast injections (n=10) or to vehicle control (n=10). Participants will undergo a biopsy to harvest volar skin for fibroblast expansion and tattooing to identify injection sites on the residual limb. Fibroblasts will be processed at the Hopkins Cellular Therapy Core Lab and volar cells primed for injection will be sent to participating centers for administration. Participants randomized to the treatment group will be treated with low-dose cells. Injections will be administered on at least 1 and up to three separate days over the course of one week. Participants randomized to the vehicle control group will receive injection of cryoprotectant. All participants will be followed at 2 weeks, 1, 2, and 3 months after the last injection. These visits will include a clinical evaluation for complications, non-invasive assessments of skin firmness and thickness, skin appearance, and patient-reported outcomes. After the final monitoring visit, individuals randomized to the vehicle control group will have the opportunity to receive the volar fibroblast injections and will be followed for an additional 3 months. The investigators hypothesize that (1) There will be no difference in the rate of serious adverse events among patients treated with volar fibroblast injections compared with patients treated with vehicle control, and (2) Patients treated with volar fibroblast injections will have firmer skin on the residual limb compared with patients tread with vehicle alone.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on chronic immunosuppressive therapies or certain medications associated with methemoglobinemia, you may not be eligible to participate.

What data supports the effectiveness of the treatment Autologous Volar Fibroblast Injection for amputee limb care?

Research on similar treatments, like autologous fibroblast injections, shows they can help improve skin conditions and scars by increasing skin elasticity and thickness, and reducing pain. These treatments have been used successfully for conditions like scars from leishmaniasis and diabetic foot ulcers, suggesting potential benefits for amputee limb care. ^{1 2 3 4 5}

Is autologous fibroblast injection safe for humans?

Autologous fibroblast injections have been shown to be safe in humans, with studies reporting no serious adverse reactions when used for treating nasolabial folds and other conditions. These injections are considered a safe option for soft tissue augmentation and scar treatment. ^{1 2 3 6 7}

How is the Autologous Volar Fibroblast Injection treatment different from other treatments for amputee limb care?

Autologous Volar Fibroblast Injection is unique because it uses the patient's own cultured fibroblasts (a type of cell that helps repair tissue) to create a living, injectable system that can provide immediate correction and continued repair of tissue deficiencies, unlike other treatments that may not offer sustained cellular growth and repair. ^{1 3 7 8 9}

Eligibility Criteria

Adults aged 18-75 with a below-the-knee amputation who use a prosthetic leg can join this trial. They must have healthy skin on the limb, not be pregnant or breastfeeding, and agree to contraception during the study. Smokers, those with certain skin diseases, active infections, bleeding disorders or taking immunosuppressants are excluded.

Inclusion Criteria

My skin is healthy and I don't have severe skin conditions or non-healing wounds.

Able to provide written informed consent

Willing and able to comply with the scheduled visits, biopsy/injection procedures, wound care instructions treatment plan, and other study procedures for the duration of the study.

Exclusion Criteria

Pregnant, lactating, or trying to become pregnant

I have a known bleeding disorder.

I have ulcers larger than 4cm across.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Biopsy and Preparation

Participants undergo a biopsy to harvest volar skin for fibroblast expansion and tattooing to identify injection sites on the residual limb

1 week

Treatment

Participants receive low-dose volar fibroblast injections or vehicle control injections over the course of one week

1 week

1-3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including clinical evaluations and non-invasive assessments

3 months

4 visits (in-person) at 2 weeks, 1, 2, and 3 months

Open-label Extension

Participants in the vehicle control group have the opportunity to receive volar fibroblast injections and are followed for an additional 3 months

3 months

Treatment Details

Interventions

• Autologous Volar Fibroblast Injection

Trial Overview The trial is testing injections of volar fibroblasts (cells from one's own body) into the residual limbs of amputees to see if it makes their skin firmer compared to a control group receiving a placebo. Participants will be followed for up to three months after treatment.

Participant Groups

Group I: Volar Fibroblast Treatment Experimental Treatment 1 Intervention

Volar fibroblasts are injected into the residual limb of transtibial amputees

Group II: Cryoprotectant Active Control 1 Intervention

Vehicle Control. Interdermal injection of cryoprotectant

Autologous Volar Fibroblast Injection is already approved in United States for the following indications:

Approved in United States as Autologous Volar Fibroblast Injection for:

• Thickening the epidermal layer at the stump site in individuals with below the knee amputations

Who Is Running the Clinical Trial?

Major Extremity Trauma Research Consortium

Lead Sponsor

Trials

32

Recruited

27,400+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Findings from Research

In a study involving 11 patients with persistent incisional pain, autologous fat injections led to a significant reduction in pain, with a mean decrease of 3.5 points on the Visual Analog Scale (VAS).

The treatment was well-received, with 74.5% of patients reporting satisfaction and no complications observed, indicating that autologous fat grafting is a safe and effective option for managing painful scars resistant to conventional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Autologous fat grafting in the surgical management of painful scar: preliminary results]. Baptista, C., Iniesta, A., Nguyen, P., et al.[2022]

Autologous fat graft injections showed some benefits for patients with painful scars and pulp atrophy following digital trauma, with a mean satisfaction score of 3.36 out of 5 regarding symptom and aesthetic improvement.

The procedure had limited impact on neuropathic pain, as indicated by the average visual analogue scale pain score of 2.91 out of 10, suggesting that while fat grafting can help with certain physical issues, it may not effectively address nerve-related pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of Autologous Fat Graft Injection(s) in Treating Sequelae of Digital Trauma: A Case Series. Lupon, E., Paoli, H., Villeneuve Bargemon, JB., et al.[2023]

Cultured autologous fibroblasts (Isolagen) have been effectively used in 1,450 patients to treat various skin issues, showing a high patient satisfaction rate of 92% regarding the correction of skin conditions after treatment.

Long-term follow-up (36 to 48 months) indicated that 70% of patients experienced continued improvement beyond the initial results, suggesting that this injectable system not only provides immediate correction but also promotes ongoing skin repair.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous cultured fibroblasts: a protein repair system. Boss, WK., Usal, H., Fodor, PB., et al.[2022]

Autologous fibroblast transplantation is a safe and effective method for improving atrophic scars caused by cutaneous leishmaniasis, with no observed side effects in the study.

The treatment led to significant improvements in epidermal thickness, melanin levels, and skin elasticity after two injections, although dermal thickness did not show improvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of fibroblast transplantation in the healing of cutaneous leishmaniasis scar: A case report. Faghihi, F., Larijani, G., Mohebbi, L., et al.[2023]

In a study involving five diabetic patients with long-standing skin ulcers, autologous skin cell implants (fibroblasts and keratinocytes) led to complete healing in 83.3% of ulcers within 21 to 120 days, demonstrating significant efficacy for difficult-to-heal diabetic ulcers.

The treatment was safe, with no adverse reactions reported, and it is a minimally invasive procedure that can be performed in an outpatient setting, making it a promising option for patients unresponsive to conventional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tissue therapy with autologous dermal and epidermal culture cells for diabetic foot ulcers. Marcelo, D., Beatriz, PM., Jussara, R., et al.[2018]

The study evaluated the safety and effectiveness of combined scar treatments using autologous derived agents like platelet-rich plasma (PRP) and lipofilling, alongside medical devices such as radiofrequency and CO2 laser, in three cases.

No adverse events were reported, and all cases showed improvement in scar quality and function, indicating that these combined methods are safe and enhance both cosmetic and functional outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined therapies in scar treatment-The role of autologous derived agents in scar remodeling: A series of cases. Surowiecka, A.[2022]

In a study involving 60 Thai women with moderate to severe nasolabial folds, autologous cultured fibroblast injections showed significant improvement in NLF volume at all follow-up points compared to baseline, indicating their effectiveness as a treatment option.

The autologous fibroblast group reported more noticeable improvements in NLFs than the hyaluronic acid filler group, with no serious adverse reactions observed, suggesting that fibroblast injections are a safe alternative with potentially longer-lasting results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot study comparing the efficacy of autologous cultured fibroblast injections with hyaluronic acid fillers for treating nasolabial folds. Wanitphakdeedecha, R., Ng, JNC., Phumariyapong, P., et al.[2023]

Autologous cultured fibroblasts can be injected to help repair acne scars and other facial imperfections, utilizing the patient's own cells for a more natural healing process.

This method offers a gradual correction of contour deformities, potentially leading to more effective and personalized treatment outcomes for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous cultured fibroblasts as cellular therapy in plastic surgery. Boss, WK., Usal, H., Chernoff, G., et al.[2022]

Autologous fat transplantation, or lipofilling, is an effective technique for correcting skin abnormalities by transferring fat from one area of the body to another, allowing for long-term improvements in skin texture.

The procedure is minimally invasive, performed on an outpatient basis under local anesthesia, and can effectively treat areas of dermal or hypodermal atrophy ranging from one to a few centimeters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Autologous fat transplantation in dermatology]. Skaria, AM., Pham, C., Braun, R., et al.[2006]

References

1. France pubmed.ncbi.nlm.nih.gov

[Autologous fat grafting in the surgical management of painful scar: preliminary results]. [2022]

2. Singapore pubmed.ncbi.nlm.nih.gov

Outcomes of Autologous Fat Graft Injection(s) in Treating Sequelae of Digital Trauma: A Case Series. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Autologous cultured fibroblasts: a protein repair system. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Efficacy of fibroblast transplantation in the healing of cutaneous leishmaniasis scar: A case report. [2023]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Tissue therapy with autologous dermal and epidermal culture cells for diabetic foot ulcers. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Combined therapies in scar treatment-The role of autologous derived agents in scar remodeling: A series of cases. [2022]

7. England pubmed.ncbi.nlm.nih.gov

A pilot study comparing the efficacy of autologous cultured fibroblast injections with hyaluronic acid fillers for treating nasolabial folds. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Autologous cultured fibroblasts as cellular therapy in plastic surgery. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

[Autologous fat transplantation in dermatology]. [2006]