Islet Cell Transplant for Type 1 Diabetes

Overseen By Piotr Witkowski, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Chicago

Must be taking: Calcineurin inhibitors

Disqualifiers: Obesity, High insulin needs, Hypertension, 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety of transplanting islet cells, which produce insulin, in individuals with Type 1 Diabetes who have already received a kidney transplant. The goal is to determine if this can control blood sugar levels without insulin shots. Participants must have had Type 1 Diabetes for over 5 years, rely on insulin, and have undergone a kidney transplant. Donors provide the islet cells, which are administered through a vein (intraportal infusion of islet cells). This research may uncover new ways to manage diabetes for those with kidney transplants. As a Phase 2 trial, it focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that participants should be on a specific type of immunosuppression medication if they have had a kidney transplant.

Is there any evidence suggesting that islet cell transplantation is likely to be safe?

Research has shown that transplanting islet cells from a donor can be safe for patients. One study found that it helps control blood sugar levels almost like normal and reduces severe low blood sugar episodes, indicating that many patients handle the treatment well. Another study confirmed its long-term safety, although patients must continue taking medication to prevent rejection of the new cells.

For the method used to deliver the islet cells, called intraportal infusion, studies have also shown long-term safety. Although patients need to take medication continuously, they generally tolerate it well. This treatment aims to manage blood sugar without the need for insulin shots.

Overall, both the treatment and the delivery method have demonstrated promising safety results in past research. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Allogenic islet cell transplantation is unique because it directly targets the root problem in Type 1 Diabetes by introducing healthy islet cells into the patient's liver, where they can produce insulin. Unlike standard treatments like insulin injections or pumps, which manage blood sugar levels externally, this approach aims to restore the body's natural insulin production. Researchers are excited about this treatment because it has the potential to significantly reduce or even eliminate the need for insulin therapy, offering a more permanent solution to managing the disease.

What evidence suggests that islet cell transplantation could be an effective treatment for Type 1 Diabetes?

Research has shown that transplanting islet cells from a donor can help manage blood sugar levels in people with type 1 diabetes. Studies have found that this method can lead to nearly normal blood sugar levels and reduce severe low blood sugar episodes. In one study, about 68% of patients no longer needed insulin for an average of 15 months. This trial will evaluate the transplantation of allogenic islet cells, which has shown long-term safety, although patients need medication to prevent rejection of the transplanted cells. Delivering these cells directly into the liver, known as intraportal infusion, has also yielded promising results, with many patients becoming insulin-independent. Overall, these findings suggest that islet cell transplantation could effectively manage type 1 diabetes. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-68 with Type 1 Diabetes, onset before age 40 and insulin-dependent for over 5 years. Participants must be at least three months post-kidney transplant, on specific immunosuppressants, and not producing their own insulin. They should have stable kidney function without severe allergies or infections, not be pregnant or planning pregnancy soon, and willing to use contraception.

Inclusion Criteria

Subjects who are able to provide written informed consent and to comply with the procedures of the study protocol

I am over 3 months post-kidney transplant and on specific immune-suppressing drugs, or I will receive a kidney and islet transplant from the same donor within 72 hours.

My kidney function has been stable for the last 3 months.

Exclusion Criteria

My blood pressure is high even with medication.

I do not have certain harmful antibodies against a transplant.

I am not pregnant, breastfeeding, or planning to become pregnant and will use effective birth control.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Islet Transplantation

Participants receive islet cell transplants from cadaver donors to improve blood sugar control

1 year

Follow-up

Participants are monitored for safety and effectiveness after transplantation

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Allogenic islet cells (human, U. Chicago)
• Intraportal infusion of islet cells

Trial Overview The study tests the safety of transplanting islet cells from deceased donors into patients who've had a kidney transplant. The goal is to see if these cells can control blood sugar levels in the body without needing insulin injections.

How Is the Trial Designed?

Group I: Allogenic islet cells (human, U. Chicago) Experimental Treatment 2 Interventions

Allogenic islet cells (human, U. Chicago) is already approved in United States, European Union, Canada, United Kingdom for the following indications:

Approved in United States as Islet Cell Transplantation for:

• Type 1 diabetes mellitus with severe hypoglycemia and impaired awareness of hypoglycemia

Approved in European Union as Islet Cell Transplantation for:

• Type 1 diabetes mellitus with recurrent severe hypoglycemia despite optimized conventional management

Approved in Canada as Islet Cell Transplantation for:

• Type 1 diabetes mellitus with severe hypoglycemia and impaired awareness of hypoglycemia

Approved in United Kingdom as Islet Cell Transplantation for:

• Type 1 diabetes mellitus with recurrent severe hypoglycemia despite optimized conventional management

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Published Research Related to This Trial

Islet transplantation can potentially cure Type 1 diabetes by replacing the destroyed insulin-secreting beta-cells, but the limited availability of donor islets has hindered its widespread use.

Recent studies indicate that xenografts, tissue stem cells, and embryonic stem cells could serve as alternative sources for insulin-producing cells, with embryonic stem cells being particularly promising due to their ability to generate large quantities of cells for transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cell-based treatments for diabetes. Jones, PM., Courtney, ML., Burns, CJ., et al.[2008]

Islet cell transplantation shows great promise as a treatment for Type 1 diabetes, with recent advancements in isolating and purifying human islet cells leading to encouraging results.

The main challenge remains the need for immunosuppression, which limits the indications for islet transplantation; however, strategies to achieve long-term graft function with minimal or no immunosuppression are being explored.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Langerhans islet preparation in cell transplantation. Penfornis, A.[2006]

Pancreas and islet transplantation are the only treatments for type 1 diabetes that can lead to insulin independence and stable blood sugar levels, but they require immunosuppressive therapy, which carries risks.

Recent advancements suggest that islet transplantation could be modified to reduce immunosuppression needs, potentially expanding its use to non-uremic type 1 diabetics, including children, while also improving quality of life and delaying complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Islet cell and pancreas transplantation in diabetes: status 1996]. Bretzel, RG.[2008]

Islet cell transplantation faces significant challenges, including insufficient yield from donor pancreases and high islet cell loss during purification, limiting its effectiveness for treating insulin-deficient diabetes.

Current islet transplants are highly susceptible to rejection and often fail shortly after transplantation, necessitating advancements in histocompatibility matching and immunosuppression techniques before they can be widely applied in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Replacement of pancreatic beta cells as treatment for diabetes mellitus: a review. Jonasson, O., Hoversten, GH.[2021]

In a study involving 7 Type 1 diabetes patients, 14 islet allografts were successfully transplanted, demonstrating initial function through C-peptide secretion and reduced insulin requirements.

Five patients were able to completely stop insulin therapy after receiving at least two grafts, indicating the potential efficacy of islet transplantation as an alternative to insulin therapy for severe Type 1 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Technique of pancreatic procurement for pancreatic islet isolation]. Hubert, T., Arnalsteen, L., Jany, T., et al.[2009]

The study demonstrated that myeloid-derived suppressor cells (MDSC) can significantly prolong the survival of islet transplants in mice without the need for immunosuppressive drugs, which are often associated with severe complications.

MDSC migration to islet grafts was dependent on the expression of the CCR2 receptor, highlighting the importance of monitoring CCR2 levels during MDSC generation for potential therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

C-C Chemokine Receptor Type 2-Dependent Migration of Myeloid-Derived Suppressor Cells in Protection of Islet Transplants. Qin, J., Arakawa, Y., Morita, M., et al.[2018]

Pancreatic islet transplantation is an effective treatment for type 1 diabetes, benefiting from advancements in isolation techniques and immunosuppression, which enhance patient outcomes.

To ensure the safety and efficacy of islet transplants, strict quality control measures must be followed throughout the isolation and transplantation process, including meeting regulatory standards for biological and drug products.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality control for clinical islet transplantation: organ procurement and preservation, the islet processing facility, isolation, and potency tests. Yamamoto, T., Horiguchi, A., Ito, M., et al.[2021]

Allogeneic islet cell transplantation is becoming a promising standard therapy for type 1 diabetes, addressing previous challenges like islet isolation efficacy and the need for immunosuppressive drugs.

Autologous islet cell transplantation is the standard treatment for patients undergoing total pancreatectomy, although it is only available at select centers, highlighting the potential for remote center options to improve access.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical allogeneic and autologous islet cell transplantation: update. Matsumoto, S.[2021]

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]

Intraportal transplantation of pancreatic islets can improve blood sugar control in type 1 diabetes, but it often leads to coagulation activation and potential islet damage, even without visible thrombosis, as observed in four patients during the study.

The study identified that pancreatic islet cells produce tissue factor (TF), which triggers clotting reactions; blocking TF with specific antibodies or inactivated factor VIIa could be a promising treatment to enhance islet transplant success and reduce the need for multiple donor islets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Production of tissue factor by pancreatic islet cells as a trigger of detrimental thrombotic reactions in clinical islet transplantation. Moberg, L., Johansson, H., Lukinius, A., et al.[2019]

Intraportal islet cell transplantation has become a more clinically relevant treatment for type 1 diabetes, thanks to advancements in protocols that enhance success rates and long-term function of islet grafts.

Recent improvements in islet transplantation techniques have made it a safer and simpler outpatient procedure compared to the more complex and risky whole-organ pancreas transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of oxygenated perfluorocarbon toward making every pancreas count. Fraker, CA., Alejandro, R., Ricordi, C.[2022]

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]

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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39936131/

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

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2213858724003413

Long-term outcomes of pancreatic islet transplantation ... Research has shown that islet transplantation alone can effectively treat some patients with type 1 diabetes, improving glycaemic control and promoting insulin ...

4. thelancet.com thelancet.com/journals/landia/article/PIIS2213-8587(24)00341-3/abstract

Long-term outcomes of pancreatic islet transplantation ... Kaplan–Meier estimates indicated graft survival rates of 86% at 1 year, 65% at 5 years, 47% at 10 years, 47% at 15 years, and 40% at 20 years.

5. diabetesjournals.org diabetesjournals.org/diabetes/article/74/5/685/158079/Cell-Benchmarks-Defining-Predictive-Outcomes-in

β-Cell Benchmarks: Defining Predictive Outcomes in Islet ... AIRpot was lower in islet transplant recipients than controls with normal glucose tolerance and remained stable for the first 4 years ...

6. diabetesjournals.org diabetesjournals.org/care/article/48/6/1007/158141/Impact-of-Islet-Transplantation-on-Diabetes

Impact of Islet Transplantation on Diabetes Complications and ... This study aimed to evaluate the impact of islet transplantation (IT) on diabetes complications, death, and cancer incidence.