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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates whether islet cell transplantation can help people with type 1 diabetes manage blood sugar without regular insulin injections. The process transplants insulin-producing cells into the liver to help control blood sugar levels. Participants will take special medications to prevent their bodies from rejecting the transplanted cells. People with type 1 diabetes who frequently experience low blood sugar episodes or have unstable blood sugar that disrupts daily life may be a good fit for this study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in diabetes care.

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 prior data suggests that islet cell transplantation is safe for type 1 diabetes?

Research has shown that transplanting islet cells from a donor can safely treat type 1 diabetes. Studies have found that this method helps control blood sugar levels and reduces the risk of severe low blood sugar episodes. Some patients even stopped needing insulin shots.

In earlier studies, patients tolerated the procedure well and experienced few serious side effects. Anti-rejection medications like ATG and alemtuzumab (Campath) protect the transplanted cells by reducing the activity of T-cells, which might attack the new cells.

Overall, evidence suggests that this treatment is well-tolerated and can effectively manage type 1 diabetes. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for Type 1 Diabetes, which often include insulin therapy and continuous glucose monitoring, the allogenic human islet cell transplant offers a groundbreaking approach by using donor islet cells to restore the body's ability to produce insulin. This treatment is unique because it directly targets the root problem by replenishing the insulin-producing cells that the immune system has destroyed. Additionally, the use of immunosuppression in this approach helps protect the transplanted islet cells from being attacked by the recipient's immune system, offering a potentially more sustainable solution. Researchers are excited about this treatment because it holds the promise of significantly reducing or even eliminating the need for lifelong insulin injections, transforming the management of Type 1 Diabetes.

What evidence suggests that islet cell transplantation could be an effective treatment for type 1 diabetes?

Research has shown that islet cell transplantation can effectively treat type 1 diabetes. Studies have found that this procedure improves blood sugar control and reduces the need for insulin shots. Some patients even stopped needing insulin altogether after the transplant. In this trial, participants will receive an allogenic human islet cell transplant with immunosuppression, using medications like ATG and alemtuzumab to protect the transplanted cells and enhance treatment success. Long-term follow-ups have demonstrated that islet transplants can lead to lasting improvements in managing blood sugar levels. Overall, these findings suggest that islet cell transplantation is a promising option for people with type 1 diabetes. ^{1 2 3 4 6}

Who Is on the Research Team?

Fouad Kandeel, MD, PhD

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10605704/

The Current Status of Allogenic Islet Cell Transplantation We review data on long-term outcomes and the ongoing challenges of allogenic islet cell and stem cell-derived islet cell transplant.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11906537/

Islet Cell Replacement and Regeneration for Type 1 Diabetes A recent phase 3 study confirmed that allogeneic islet transplantation is a safe and effective treatment for patients with T1D and unstable ...

3. diabetesjournals.org diabetesjournals.org/diabetes/article/74/7/1068/158190/Advances-in-Cell-Replacement-Therapies-for

Advances in Cell Replacement Therapies for Diabetes Health authorities in several countries have approved deceased donor islet transplantation for treating patients with type 1 diabetes and ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1600613522088049

Ten-year outcomes of islet transplantation in patients with ... With a 10-year follow-up in a multicentric network, islet transplantation provided sustained improvement of glycemic control and was efficient to prevent ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT01909245

NCT01909245 | Islet Cell Transplant for Type 1 Diabetes 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 ...

6. journals.lww.com journals.lww.com/transplantationdirect/fulltext/2025/03000/efficacy_and_safety_of_allogeneic_islet.6.aspx

Efficacy and Safety of Allogeneic Islet Transplantation... Islet transplantation provided near-normal glycemic control and protection against severe hypoglycemic events in patients with type 1 diabetes mellitus in this ...