Tissue Engineered Vascular Grafts for Heart Disease

(TEVG-2 Trial)

Overseen By Joanne Chisolm, MSN, RN

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Nationwide Children's Hospital

Must not be taking: Bisphosphonates

Disqualifiers: Acute renal failure, Pacemaker, 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: Unknown

Duration: Immediate post-operative period

24 Participants Needed

Trial Summary

What is the purpose of this trial?

A single arm clinical trial evaluating the safety and efficacy of the second generation TEVG as vascular conduits for extracardiac total cavopulmonary connection.

Will I have to stop taking my current medications?

The trial may require you to stop taking certain medications if they could interfere with the study, such as bisphosphonates (medications that prevent bone loss). It's best to discuss your current medications with the trial investigator to see if any changes are needed.

What data supports the effectiveness of the treatment Second-Generation Tissue Engineered Vascular Grafts for heart disease?

Research shows that tissue-engineered vascular grafts (TEVGs) can transform into vessels that function like natural ones and have the ability to grow, which is promising for heart surgeries in children. Although there are challenges like blood clots and vessel thickening, studies in both animals and humans have shown encouraging results, suggesting TEVGs could eventually replace traditional grafts. ^{1 2 3 4 5}

Is the use of tissue-engineered vascular grafts safe in humans?

Tissue-engineered vascular grafts (TEVGs) have shown an excellent safety profile in clinical trials, although about 16% of grafts may experience stenosis (narrowing) within the first seven years after implantation. ^{2 4 5 6 7}

How is the Second-Generation Tissue Engineered Vascular Grafts treatment different from other treatments for heart disease?

Second-Generation Tissue Engineered Vascular Grafts (TEVGs) are unique because they are made from biologically active cells and biodegradable scaffolds, allowing them to grow and repair themselves, unlike traditional synthetic grafts that cannot remodel or self-repair. This makes TEVGs potentially more effective, especially for smaller diameter grafts, as they can adapt and integrate better with the body's natural tissues. ^{1 2 4 5 6}

Research Team

Christopher Breuer, MD

Principal Investigator

Nationwide Children's Hospital

Mark Galantowicz, MD

Principal Investigator

Nationwide Children's Hospital

Toshiharu Shinoka, MD/PhD

Principal Investigator

Nationwide Children's Hospital

Eligibility Criteria

This trial is for children with certain heart defects who need a special surgery called extracardiac total cavopulmonary connection. They must be able to follow the study plan and not have urgent medical issues, pacemakers, severe heart valve problems, other serious health conditions, or need graft sizes outside of 12-24 mm. Kids with high lung blood pressure or abnormal veins can't join.

Inclusion Criteria

Patient and/or legal guardian must voluntarily provide informed consent/assent for participation in the study.

I am eligible for a specific heart surgery to improve blood flow.

Exclusion Criteria

Patient has a history of another condition or significant medical problem that, in the opinion of the investigator, precludes compliance with protocol-specified procedures.

Patient or parent/legal guardian is, in the opinion of the investigator, unable to comply with protocol evaluations.

You need a graft that is not between 12 and 24 millimeters in diameter.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients with single ventricle cardiac anomalies undergo EC TCPC using a tissue engineered conduit

Immediate post-operative period

In-patient surgical procedure

Follow-up

Participants are monitored for safety and effectiveness after treatment, including adverse events and graft performance

2 years

Regular follow-up visits at Nationwide Children's Hospital

Interim Analysis

Interim analysis to assess early graft-related complications in the first 6 enrolled patients

Up to 6 months

Treatment Details

Interventions

• Second-Generation Tissue Engineered Vascular Grafts

Trial Overview The study tests second-generation tissue engineered vascular grafts (TEVG) in kids needing heart surgery to connect large veins to their lungs. It's checking if these new grafts are safe and work well over two years without using different treatment groups.

Participant Groups

Group I: Tissue Engineered Vascular Grafts Experimental Treatment 1 Intervention

Second-Generation Tissue Engineered Vascular Grafts is already approved in United States for the following indications:

Approved in United States as Second-Generation TEVG for:

• Extracardiac Total Cavopulmonary Connection

Who Is Running the Clinical Trial?

Nationwide Children's Hospital

Lead Sponsor

Trials

354

Recruited

5,228,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Gunze Limited

Collaborator

Trials

3

Recruited

30+

Findings from Research

In a study involving 25 patients with single ventricle physiology, tissue-engineered vascular grafts were successfully implanted as conduits, showing no graft-related mortality over a mean follow-up of 5.8 years.

The main issue observed was graft stenosis, which occurred in four patients but was treatable with percutaneous angioplasty, indicating that while the grafts are generally safe, monitoring for stenosis is essential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Late-term results of tissue-engineered vascular grafts in humans. Hibino, N., McGillicuddy, E., Matsumura, G., et al.[2022]

Small-diameter tissue-engineered vascular grafts (TEVGs) are still not widely used in clinical settings, despite significant advancements in tissue engineering, highlighting a critical unmet need in medical treatments.

The review emphasizes the potential role of stem cells in developing TEVGs and suggests future research directions to enhance the viability and effectiveness of these grafts for clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stem cells for tissue engineered vascular bypass grafts. Askari, F., Solouk, A., Shafieian, M., et al.[2018]

Tissue-engineered vascular grafts (TEVGs) show potential for creating functional blood vessels in children, with a study using a lamb model revealing that the polymer scaffold loses structural integrity within 26 weeks, while fragments can last up to 52 weeks.

Neotissue formation initially results from an inflammatory response to the scaffold, but as it degrades, the remodeling process shifts to being driven by mechanical forces, ultimately leading to a neovessel that behaves like a natural blood vessel and supports biological growth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tissue engineered vascular grafts transform into autologous neovessels capable of native function and growth. Blum, KM., Zbinden, JC., Ramachandra, AB., et al.[2023]

Endothelialization is crucial for preventing thrombosis in tissue-engineered vascular grafts (TEVGs), especially those with small diameters (<6 mm), which are prone to complications after transplantation.

The review highlights the importance of selecting appropriate types of endothelialization and seed cells to enhance the long-term success and patency rates of TEVGs, suggesting that tailored approaches could improve outcomes based on graft size and length.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selection of different endothelialization modes and different seed cells for tissue-engineered vascular graft. Cai, Q., Liao, W., Xue, F., et al.[2021]

Tissue-engineered vascular grafts (TEVGs) show potential advantages over traditional synthetic grafts, including reduced complications and improved integration with the body.

Current research, including both animal and human studies, indicates promising results for TEVGs, but further development is necessary before they can be widely adopted as replacements for conventional grafts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Current Status of Tissue-Engineered Vascular Grafts. Jaspan, VN., Hines, GL.[2015]

Tissue-engineered vascular grafts (TEVGs) show promise in overcoming the limitations of conventional synthetic grafts, such as poor remodeling and patency issues, by utilizing biologically active cells and biodegradable scaffolds.

Recent advancements in TEVG technology, including improved scaffold materials and design, have led to successful clinical trials, indicating their potential for clinical applications and the development of 'off-the-shelf' solutions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tissue engineered vascular grafts: current state of the field. Ong, CS., Zhou, X., Huang, CY., et al.[2018]

The first clinical trial of tissue engineered vascular grafts (TEVG) using autologous bone marrow-derived cells showed an excellent safety profile, indicating that this approach is safe for patients with cardiovascular diseases.

However, about 16% of the grafts experienced stenosis (narrowing) within the first seven years, highlighting a significant complication that needs further research to improve the design and function of future TEVGs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vascular tissue engineering: towards the next generation vascular grafts. Naito, Y., Shinoka, T., Duncan, D., et al.[2011]

References

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

Late-term results of tissue-engineered vascular grafts in humans. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Stem cells for tissue engineered vascular bypass grafts. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Tissue engineered vascular grafts transform into autologous neovessels capable of native function and growth. [2023]

4. China pubmed.ncbi.nlm.nih.gov

Selection of different endothelialization modes and different seed cells for tissue-engineered vascular graft. [2021]

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

The Current Status of Tissue-Engineered Vascular Grafts. [2015]

6. England pubmed.ncbi.nlm.nih.gov

Tissue engineered vascular grafts: current state of the field. [2018]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Vascular tissue engineering: towards the next generation vascular grafts. [2011]