Esophageal Implant for Esophageal Reconstruction

Recruiting at 1 trial location

Overseen By William L Fodor, Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Biostage, Inc.

Disqualifiers: Diabetes, Connective tissue disorders, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new esophageal implant called the Cellspan™ Esophageal Implant (CEI), which combines a synthetic scaffold with a person's own stem cells to help regrow a damaged esophagus. It is designed for individuals needing a section of their esophagus rebuilt, particularly those with stubborn esophageal narrowing or holes that have not improved after other treatments. Ideal candidates for this trial are those who have had at least three different treatments fail and require surgery to repair a short part of their esophagus. The trial aims to determine if this implant can safely and effectively aid in healing the esophagus and restoring its function. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

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

What prior data suggests that the Cellspan™ Esophageal Implant is safe for esophageal reconstruction?

Research has shown that the Cellspan™ Esophageal Implant (CEI) is still undergoing safety testing in humans. Earlier studies found that similar esophageal grafts can be successfully used for esophageal reconstruction in people. However, since this is the first human trial for the CEI, information on patient tolerance and potential side effects remains limited.

An independent Data Monitoring Committee closely monitors this trial to ensure safety. They use a step-by-step approach to enroll participants, carefully reviewing each case before proceeding. This process helps identify and address any safety issues quickly. While the study aims to determine the safety of the CEI, the absence of previous human trials means potential participants should be aware of the uncertainties involved. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for esophageal reconstruction involve complex surgeries or grafts using tissue from other parts of the body, which can be invasive and come with significant recovery time. The Cellspan™ Esophageal Implant (CEI) is unique because it offers a potentially less invasive alternative that uses a synthetic scaffold to encourage the body's own cells to regenerate the esophagus. This innovative approach not only reduces the need for extensive surgery but also aims to improve healing by harnessing the body's natural regenerative processes. Researchers are excited about this treatment because it could lead to quicker recovery times and fewer complications, revolutionizing how we approach esophageal reconstruction.

What evidence suggests that the Cellspan™ Esophageal Implant is effective for esophageal reconstruction?

Research has shown that the Cellspan™ Esophageal Implant (CEI), which participants in this trial will receive, has yielded promising results in animal studies. In pigs, the implant facilitated tissue regrowth after esophagus removal, forming a new, continuous tube-like structure. Early findings also suggest that mesenchymal stem cells can repair the esophagus rapidly, in about two weeks. Although data on humans is limited, these results provide a strong basis for expecting similar outcomes in people. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

This trial is for adults over 18 who've tried at least three treatments without success for esophageal conditions like strictures, perforations, or fistulas. They must need and be able to undergo a short segment esophageal reconstruction within the thoracic cavity and be considered high-risk for standard procedures.

Inclusion Criteria

I have tried at least 3 treatments for my esophagus condition without success.

I am eligible for a surgery to remove a small part of my esophagus.

I need surgery to fix my esophagus due to severe damage or blockage.

Exclusion Criteria

I had a procedure for Barrett's esophagus less than a year ago.

I have implants near the surgery area that could interfere with the healing.

Life expectancy of less than 1 year

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Implantation and Initial Monitoring

Participants undergo the CELLSPAN Esophageal Implant procedure and are monitored for immediate post-surgical outcomes

6 weeks

Regular monitoring visits

Follow-up

Participants are monitored for safety and effectiveness after treatment, including imaging and endoscopic evaluations

3 months

Monthly visits

Long-term Follow-up

Participants are followed for a minimum of 2 years post-implant surgery to assess long-term safety and efficacy

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Cellspan™ Esophageal Implant (CEI)

Trial Overview

The study tests the CELLSPAN Esophageal Implant (CEI), which uses a patient's stem cells on a synthetic scaffold to regenerate part of the esophagus. It's a first-in-human trial with continuous safety monitoring by an independent committee across multiple U.S. centers.

How Is the Trial Designed?

Group I: Short Segment Esophageal Replacement in patients that have had a previous partial esophagectomy Experimental Treatment 1 Intervention

Group II: Short Segment Esophageal Replacement in patients requiring a full reconstruction of the esophagus Experimental Treatment 1 Intervention

Cellspan™ Esophageal Implant (CEI) is already approved in United States, European Union for the following indications:

Approved in United States as Cellspan Esophageal Implant for:

• Short segment esophageal replacement
• Refractory benign esophageal strictures (RBES)
• Esophageal perforation
• Chronic/persistent esophageal fistula

Approved in European Union as Cellspan Esophageal Implant for:

• Orphan designation for esophageal reconstruction

Who Is Running the Clinical Trial?

Biostage, Inc.

Lead Sponsor

Trials

1

Recruited

10+

Harvard Apparatus Regenerative Technology, Inc.

Lead Sponsor

Trials

1

Recruited

10+

Published Research Related to This Trial

The CellspanTM Esophageal Implant (CEI) successfully stimulated tissue regeneration in a porcine model after segmental resection of the esophagus, leading to a fully epithelialized lumen by 90 days and complete tissue architecture restoration by 365 days.

The mechanical strength of the regenerated tissue was comparable to that of the native esophagus, indicating that the CEI not only facilitated healing but also restored the functional integrity of the esophagus over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biomechanics of regenerated esophageal tissue following the implantation of a tissue engineered CellspanTM Esophageal Implant. Meng, L., Frohbergh, M., Villarraga, M., et al.[2022]

Tissue engineering offers a promising alternative to traditional esophageal replacement methods by using a combination of acellular matrices and autologous cells, showing the most success in creating esophageal substitutes.

Future developments may include 'intelligent matrices' that promote tissue regeneration without the need for implantation, leveraging the properties of mesenchymal stem cells to enhance healing and reduce inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Esophageal tissue engineering: Current status and perspectives. Poghosyan, T., Catry, J., Luong-Nguyen, M., et al.[2022]

A patient successfully received a tissue-engineered esophageal graft made from autologous adipose-derived mesenchymal stromal cells (Ad-MSCs) and a polyurethane scaffold, demonstrating the potential for esophageal regeneration after a complex tumor resection.

Histological analysis 7.5 months post-implantation showed complete luminal epithelialization and partial regeneration of esophageal tissue, indicating that the graft effectively supports healing and tissue growth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-Human Segmental Esophageal Reconstruction Using a Bioengineered Mesenchymal Stromal Cell-Seeded Implant. Aho, JM., La Francesca, S., Olson, SD., et al.[2022]

This study successfully created tissue-engineered esophageal constructs using cells isolated from donor rat esophagus, which were cultured and integrated into the host tissue after transplantation, allowing recipients to resume normal feeding.

The engineered constructs demonstrated the ability to develop into multiple cell types (epithelial, smooth muscle, and glial), indicating their potential for treating severe esophageal conditions in both pediatric and adult patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biomimetic and synthetic esophageal tissue engineering. Jensen, T., Blanchette, A., Vadasz, S., et al.[2018]

The Cellspan Esophageal ImplantTM (CEI) was successfully implanted in piglets, showing promising results in restoring esophageal continuity with complete epithelialization of the lumenal surface by day 90 and ongoing tissue remodeling over a 1-year period.

CT imaging and histological evaluations confirmed the safety and efficacy of the CEI, as it allowed for normal growth and restoration of oral nutrition in the animals, indicating a viable alternative to traditional surgical interventions for esophageal defects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Esophageal regeneration following surgical implantation of a tissue engineered esophageal implant in a pediatric model. Sundaram, S., Jensen, T., Roffidal, T., et al.[2022]

Iodine-125 seed implantation demonstrated a 100% dysphagia remission rate at half a month post-treatment, significantly outperforming conventional treatments like radiotherapy and chemotherapy, which had much lower remission rates.

No serious adverse events were reported with iodine-125 seed implantation, indicating it is a safer option compared to conventional therapies that had higher incidences of myelosuppression and gastrointestinal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the Therapeutic Effects of Iodine-125 Seed Implantation and Conventional Radiochemotherapy for Advanced Esophageal Cancer. Han, LQ., Wang, CH., Cui, TT., et al.[2022]

A novel esophageal substitute made from a decellularized porcine scaffold seeded with bone marrow-derived mesenchymal stromal cells (BM-MSCs) showed promising results in replicating the muscle layer of the esophagus, indicating potential for functional restoration.

Despite some complications like esophageal substenosis in both non-seeded and seeded groups, the seeded scaffolds demonstrated better muscle layer regeneration, suggesting that cell seeding enhances the healing process compared to non-seeded scaffolds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful muscle regeneration by a homologous microperforated scaffold seeded with autologous mesenchymal stromal cells in a porcine esophageal substitution model. Marzaro, M., Algeri, M., Tomao, L., et al.[2022]

Citations

1.

mayo.edu

mayo.edu/research/clinical-trials/cls-20550192

Safety and Feasibility Study of the CELLSPAN Esophageal ...

This is a single arm, unblinded, multicenter, prospective first-in-human (FIH) feasibility study to be performed at a maximum of 5 centers in the United States.

2.

trialx.com

trialx.com/clinical-trials/listings/279368/safety-and-feasibility-study-of-the-cellspan-esophageal-implant-cei-in-patients-requiring-short-segment-esophageal-replacement/

Safety and Feasibility Study of the CELLSPAN Esophageal ...

A clinical trial is a study designed to test specific interventions or treatments' effectiveness and safety, paving the way for new, innovative ...

3.

trialfinder.panfoundation.org

trialfinder.panfoundation.org/en-US/trial/listing/500256

Safety and Feasibility Study of the CELLSPAN Esophageal ...

Primary outcome measures · The number of patients who develops continuous biologic neo-conduit within the esophagus based on CT/MRI imaging and ...

4.

withpower.com

withpower.com/trial/phase-1-esophageal-diseases-5-2023-05764

Esophageal Implant for Esophageal Reconstruction

The CellspanTM Esophageal Implant (CEI) successfully stimulated tissue regeneration in a porcine model after segmental resection of the esophagus, leading to a ...

5.

sciencedirect.com

sciencedirect.com/science/article/pii/S2468498822000105

Early tissue growth and cell fate determination following ...

A Mesenchymal Stromal Cell (MSC) seeded Implant can repair the esophagus following a segmental resection and restore the esophageal conduit within 14 days.

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8474397/

First-in-Human Segmental Esophageal Reconstruction Using ...

In this case report, we found that a clinical-grade, tissue-engineered esophageal graft can be used for segmental esophageal reconstruction in a human patient.