Islet Cell Transplant for Type 1 Diabetes

(TCD Trial)

Overseen By Fouad Kandeel, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

Must be taking: Anti-rejection medications

Must not be taking: Chronic anticoagulants

Disqualifiers: Obesity, Kidney dysfunction, Cardiovascular disease, 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

Compensation: Varies

Number of Visits: Unknown

10 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you will need to take anti-rejection medications and comply with a post-transplant regimen, which may affect your current medication plan.

What data supports the effectiveness of the islet cell transplant treatment for Type 1 Diabetes?

Research shows that allogeneic islet transplantation can be an effective therapy for Type 1 Diabetes, with improvements in success rates over time. However, challenges like limited donor availability and the need for better islet survival and function remain. ^{1 2 3 4 5}

Is islet cell transplantation safe for humans?

Islet cell transplantation has been performed for about 30 years and is considered a treatment option for certain patients with type 1 diabetes. However, the main safety concern is the need for immunosuppression (medications to prevent the body from rejecting the transplant), which can have significant side effects. Improvements in the procedure and management of these risks are ongoing. ^{1 2 6 7 8}

How is the islet cell transplant treatment different from other treatments for Type 1 Diabetes?

Islet cell transplant treatment is unique because it involves transplanting insulin-producing cells from a deceased donor to help restore normal blood sugar levels in people with Type 1 Diabetes. Unlike other treatments that require ongoing insulin injections, this approach aims to provide a more permanent solution by replacing the damaged cells, although it requires managing immune system reactions to prevent rejection. ^{1 2 9 10 11}

What is the purpose of this trial?

City of Hope National Medical Center, located in Duarte, CA, is hosting a clinical study on islet cell transplantation, an experimental procedure being evaluated as a treatment for patients with type 1 diabetes. Islet cell transplantation involves taking insulin-producing cells from organ donors and transplanting them into the liver of a patient with diabetes. Once transplanted, the islets produce insulin, which can improve blood sugar control and eliminate the need to inject insulin or use an insulin pump. Anti-thymocyte globulin (ATG) and alemtuzumab (Campath) are anti-rejection medications that work by decreasing a patient's T-cells. T-cells are special white blood cells that recognize and destroy unwanted things like infections but can also attack transplanted cells and organs. Reducing the number of T-cells at the time of transplant may protect islets and improve long-term transplant success. In previous research studies, islet transplantation has been successful in reducing low blood sugar episodes, improving overall blood sugar control, and in some cases, allowing patients with type 1 diabetes to stop taking insulin. The purpose of this study is to determine if islet cell transplantation using ATG or alemtuzumab, along with additional medications to prevent the body from rejecting the transplanted cells, is a safe and effective treatment for type 1 diabetes. Study participants may receive up to three islet transplants and will be followed for five years to monitor blood sugar control, islet transplant function, and changes in quality of life.

Research Team

Fouad Kandeel, MD, PhD

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

Adults aged 18-68 with Type 1 diabetes for at least 5 years, willing to follow a strict post-transplant regimen including anti-rejection meds, frequent clinic visits, and contraception use. Excludes those with significant heart or kidney issues, high BMI (>33), substance abuse, certain infections or blood disorders, pregnancy/breastfeeding women, and untreated psychiatric illnesses.

Inclusion Criteria

I am committed to following a strict post-transplant care plan, including medication, contraception, and regular health monitoring.

I have had Type 1 diabetes for 5 years or more.

Exclusion Criteria

I have anemia or another blood disorder that needs treatment.

I have a high risk of bleeding or I am on long-term blood thinners.

I have serious kidney problems.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Transplantation

Participants receive up to three islet cell transplants with immunosuppression using ATG or alemtuzumab

Varies per transplant

Follow-up

Participants are monitored for blood sugar control, islet transplant function, and changes in quality of life

5 years

Treatment Details

Interventions

• Alemtuzumab (Campath)
• Allogenic Human Islet Cells
• Anti-thymocyte globulin (ATG)

Trial Overview The trial is testing if transplanting insulin-producing cells into the liver can help control blood sugar in Type 1 diabetes patients. It involves anti-rejection drugs (ATG or alemtuzumab) plus other medications to protect the transplanted cells. Participants may get up to three transplants and are monitored for five years.

Participant Groups

Group I: Single Arm Study Experimental Treatment 3 Interventions

Allogenic Human Islet Cell Transplant with immunosuppression

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

University of California, Los Angeles

Collaborator

Trials

1,594

Recruited

10,430,000+

Findings from Research

In a study of 44 patients with Type 1 Diabetes who underwent islet transplantation, a larger islet infusion volume was negatively associated with graft survival, suggesting that smaller infusion volumes may be more effective when combined with improved immunosuppressive protocols.

The administration of Exenatide and Filgrastim was positively associated with better graft survival, indicating that these treatments could enhance the success of islet transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

G-CSF and Exenatide Might Be Associated with Increased Long-Term Survival of Allogeneic Pancreatic Islet Grafts. Zoso, A., Serafini, P., Lanzoni, G., et al.[2020]

Islet allotransplantation has been performed for about 30 years to treat brittle type 1 diabetes, but its use is still limited to select patients due to challenges like the need for lifelong immunosuppression.

Research is ongoing to improve islet production, engraftment, and long-term function, including strategies like co-transplanting beta cell progenitors to enhance graft survival, with clinical trials anticipated in the near future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Islet transplantation 30 years after the first transplants. Antonioli, B., Galuzzi, M.[2019]

Islet transplantation outcomes for type 1 diabetes have improved over time, with insulin independence rates increasing from 27% in 1999-2002 to 44% in 2007-2010, indicating enhanced efficacy of the procedure.

Safety outcomes also improved, as evidenced by a lower rate of islet reinfusion (48% in 2007-2010 compared to 60-65% in earlier years) and a reduction in adverse events, suggesting a more favorable risk profile for recent transplant recipients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improvement in outcomes of clinical islet transplantation: 1999-2010. Barton, FB., Rickels, MR., Alejandro, R., et al.[2022]

Pancreatic islet transplantation has become a viable treatment option for diabetes, showing significant progress since the initial proof of principle was established.

Current clinical trials are focused on refining recipient selection, improving islet graft production, and managing immunosuppression to enhance the success rates of islet transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Islet transplantation: current status and future directions. Hatipoglu, B., Benedetti, E., Oberholzer, J.[2021]

In a study of 35 type 1 diabetic patients who received islet cell transplants from a median of 6 donors, the withdrawal of immunosuppressants led to low rates of allosensitization as measured by the CDC assay (only 6% positivity for class I antibodies).

However, a high rate of allosensitization was observed using the Luminex assay, with 72% of patients testing positive for class I or class II antibodies, particularly associated with lower β-cell purity in the grafts, while the use of steroids helped reduce the positivity for class I antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictive factors of allosensitization after immunosuppressant withdrawal in recipients of long-term cultured islet cell grafts. Hilbrands, R., Gillard, P., Van der Torren, CR., et al.[2016]

References

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

G-CSF and Exenatide Might Be Associated with Increased Long-Term Survival of Allogeneic Pancreatic Islet Grafts. [2020]

2. Italy pubmed.ncbi.nlm.nih.gov

Islet transplantation 30 years after the first transplants. [2019]

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

Twenty years of clinical islet transplantation at the Diabetes Research Institute--University of Miami. [2021]

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

Potential of mesenchymal stromal cells for improving islet transplantation outcomes. [2019]

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

Improved human pancreatic islet isolation for a prospective cohort study of islet transplantation vs best medical therapy in type 1 diabetes mellitus. [2011]

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

Improvement in outcomes of clinical islet transplantation: 1999-2010. [2022]

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

Islet transplantation: current status and future directions. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Sertoli cell-induced reversal of adult rat pancreatic islet beta-cells into fetal-like status: potential implications for islet transplantation in type I diabetes mellitus. [2006]

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

A view on beta cell transplantation in diabetes. [2021]

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

Predictive factors of allosensitization after immunosuppressant withdrawal in recipients of long-term cultured islet cell grafts. [2016]

11. Egypt pubmed.ncbi.nlm.nih.gov

Tolerance-inducing strategies in islet transplantation. [2021]