Multicenter Trial Evaluating the Safety and Efficacy of Autologous Volar Fibroblast Injection Into the Terminal Limb of Amputees.

A Phase 2 Multicenter Randomized Single Arm Crossover Trial Evaluating the Safety and Efficacy of Autologous Volar Fibroblast Injection Into the Terminal Limb of Amputees

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.

Study Overview

• Status: Recruiting
• Conditions: Amputation
• Intervention / Treatment: Combination product: Autologous Volar Fibroblast Injection into the Terminal Limb of Amputees

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Dana Alkhoury; Phone Number: 410- 955-7498; Email: dalkhou1@jhu.edu
• Study Contact Backup: Name: Luis Garza, md; Email: lag@jhmi.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • Johns Hopkins Hospital
      • Contact: Luis Garza, md; Email: lag@jhmi.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

1. Ages 18 to 75, inclusive
2. Must have a transtibial amputation
3. Must be using a prosthesis within the vicinity of 3 months or have had osteo-integration of a prosthetic in place for 1 month
4. In the opinion of the investigator, must be medically able to undergo the administration of study material determined by laboratory tests obtained up to 14 days before baseline for which the investigator identified no clinically significant abnormality.
5. Able to provide written informed consent
6. Females of childbearing potential must: have a negative pregnancy test at screening agree to not become pregnant or breastfeed for the period of the study through 1 month after completion of the study be willing to use a reliable form of contraception during the study.
7. Has healthy skin on the residual limb and is free of severe and active skin disease (excluding those on the residual limb) such as extreme and active eczema or psoriasis, active non-healing wounds, lichen planus, a history of keloid scare formation or lupus as determined by the investigator or study nurse.
8. 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:

1. A skin erosion deeper than the skin dermis.
2. Ulcers exceeding 4cm in diameter or 2cm in radius
3. Non circular ulcers that cannot tolerate a 1cm margin at all sides
4. Having received any investigational drug within 30 days prior to study entry
5. An allergy history to any study materials including local anesthetic, dimethyl sulfoxide, human albumin, or bovine constituents, hetastarch, or EMLA (lidocaine 2.5% and prilocaine 2.5%).
6. Pregnant, lactating, or trying to become pregnant
7. A history of keloid formation
8. Having a significant medical history that the investigator feels is not safe for study participation (for example, some forms of autoimmune conditions, metastatic cancer, infectious diseases such as HIV, HTLV I/II, Hepatitis B, Hepatitis C).
9. Autoimmune diseases affecting the skin such as lupus.
10. Presence of necrotic ischemic tissue on any stump ulcers, and/or capillary refill on stump skin of greater than 3 seconds
11. Active infection of the residual limb (e.g. osteomyelitis, wound or skin condition with surrounding swelling, erythema, drainage, pain, gangrenous tissue or fever).
12. Active smoker during the study (this includes e cigarettes and any type of tobacco use)
13. We will also exclude those who are on chronic immunosuppressive therapies such as oral steroids, but also those on chronic topical steroids in the area of investigation.
14. Amputees with symptomatic neuromas of the terminal limb within the last 3 months.
15. Known bleeding disorder.
16. Have a history of congenital or idiopathic methemoglobinemia, glucose-6-phosphate deficiencies, or use of medications associated with drug-induced methemoglobinemia. (specifically: Sulfonamides, Acetaminophen, Acetanilid, Aniline dyes, Benzocaine, Chloroquine, Dapsone, Naphthalene, Nitrates and Nitrites, Nitrofurantoin, Nitroglycerin, Nitroprusside, Pamaquine, Paraaminosalicylic acid, Phenacetin, Phenobarbital, Phenytoin, Primaquine, or Quinine.)
17. Quadriplegics

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Volar Fibroblast Treatment; Volar fibroblasts are injected into the residual limb of transtibial amputees	Combination product: Autologous Volar Fibroblast Injection into the Terminal Limb of Amputees; Autologous Volar Fibroblasts Treatment- harvested from patient's biopsied volar skin. Intradermal injection of Volar fibroblasts in the residual limb of transtibial amputees.; Other Names: Autologous Volar Fibroblast Treatment
No Intervention: Cryoprotectant; Vehicle Control. Interdermal injection of cryoprotectant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety assessment of complications and adverse events associated with Volar Fibroblast injections	Safety will be evaluated by routinely assessing all complications at each study visit. Minor and expected complications may include local injection reactions like bruising and erythema, swelling and pain. Minor complications that are not expected include local small hemorrhage (x<1mL), edema, nodules, papules, irritation, dermatitis, pruritus, and cellulitis. Serious Adverse Events are defined as unexpected AND serious AND related or possibly related to the study treatment. These may include but are not limited to osteomyelitis.	3 months from the injection visit
Efficacy of autologous volar fibroblasts for increasing skin firmness in individuals with a transtibial amputation.	Efficacy will be determined by treatment group difference in the pre- post-change in skin firmness at three months post injection. Skin firmness is the level of resistance as measured by a non-invasive hand-held durometer	Baseline through 3 months from the injection visit

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Skin thickness	thickness of epidermal layer as measured by non-invasive OCT images	Baseline through 3 months from the injection visit
Skin appearance	A photo of the treated area by trained research staff to monitor for changes in skin characteristics such as erythema and wound recurrence. Skin disturbances around the treated area will be measured by taking a photo of the area with ruler in view.	3 months from the injection visit
Participant reported health care utilization	Participants will be asked how often they stayed overnight in a hospital for treatment of a residual limb issue, and how often they saw a physical therapist, physical medicine and rehabilitation clinician, orthotist/prosthetist and wound care specialist, including at-home nurses for treatment related to the amputation.	3 months from the injection visit
Participant reported prosthesis use	Participants will be asked how often a prosthesis was worn during a typical week/day.	3 months from the injection visit
Participant reported use of support devices	participants will be asked about their use of ambulatory devices and how often a wheelchair was used.	3 months from the injection visit
Participant reported medication and treatment	Participants will be asked how often they use mediations and other treatment modalities to treat skin problems on the residual limb.	3 months from the injection visit
Participant reported physical function and activity	Participants will complete the 12-item short form of the Prosthetic Limb Users Survey of Mobility (PLUS-M), a validated self-reported instrument for measuring mobility in adults with lower limb amputation. PLUS-M questions assess respondents perceived ability to carry out actions that require use of both lower limbs, ranging from household ambulation to outdoor recreational activities.	3 months from the injection visit
Participant reported quality of life, mood and pain	Participants will complete the Patient Reported Outcomes Measurement Information System (PROMIS) 29 item short form Health related quality of life measure (HRQoL), PROMIS-29. This validated measure includes seven HRQoL domains: physical function, anxiety, depression, fatigue, sleep disturbance, social functioning and pain, and the pain domain has two subdomains (interference and intensity)	3 months from the injection visit
Participant reported skin irritation	Participants will be asked about the impact of skin irritation on the residual limb, drawing on questions from the Prosthetic Evaluation Questionnaire (PEQ), and the Dermatology Life Quality Index (DLQI).	3 months from the injection visit

Collaborators and Investigators

• Sponsor: Major Extremity Trauma Research Consortium
• Collaborators: United States Department of Defense

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2022
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: March 23, 2021
• First Submitted That Met QC Criteria: April 7, 2021
• First Posted (Actual): April 9, 2021

Study Record Updates

• Last Update Posted (Estimated): October 14, 2025
• Last Update Submitted That Met QC Criteria: October 10, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: W81XWH1820055

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Study results will be published and disseminated in accordance with the METRC publication and data sharing policy guide

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No