Islet Cell Transplant for Type 1 Diabetes

Overseen By Piotr Witkowski, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Chicago

Disqualifiers: Obesity, Hypertension, Kidney disease, others

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

Compensation: Varies

Number of Visits: Unknown

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety of islet cell transplants to help people with Type 1 diabetes control their blood sugar without insulin shots. Islets are special groups of cells in the pancreas that produce insulin. In this study, these cells will be sourced from donors and infused into participants. The trial seeks individuals with Type 1 diabetes who have relied on insulin for at least five years and experience severe low blood sugar episodes. As an unphased trial, participants can contribute to groundbreaking research that could transform diabetes treatment.

Will I have to stop taking my current medications?

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

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

Previous studies have shown promise for islet cell transplantation in people with Type 1 diabetes. Research indicates that this procedure can help patients maintain better blood sugar levels and reduce severe low blood sugar episodes.

Regarding safety, studies report that islet transplantation is generally well-tolerated. For example, one study found a 92% overall survival rate over about 13 years, demonstrating good long-term outcomes. However, some side effects often relate to the need for ongoing medication to prevent rejection of the transplanted cells.

For the intraportal infusion method, which delivers cells into the liver, research shows it can prevent severe low blood sugar and improve blood sugar control. Although continuous medication is necessary, studies highlight the procedure's good long-term safety profile.

Overall, these methods have shown safety, but participants should be aware of the potential need for ongoing treatment to maintain the transplant's benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard insulin therapy for managing Type 1 Diabetes, islet cell transplantation offers a unique approach by using allogenic islet cells from donors. This treatment targets the underlying issue by transplanting functional insulin-producing cells directly into the liver through intraportal infusion, potentially reducing or eliminating the need for insulin injections. Researchers are excited because this could lead to more stable blood glucose levels and a better quality of life for patients.

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

Studies have shown that islet cell transplantation can help manage type 1 diabetes by improving blood sugar control. Research indicates that patients who received islet transplants often achieve blood sugar levels close to normal and experience fewer severe low blood sugar episodes. In large trials, about 74% of patients no longer needed insulin shots, achieving insulin independence. Long-term studies reveal that many patients retain some function of the transplanted cells, with 86% of these cells surviving after one year and 47% after ten years. In this trial, participants will receive allogenic islet cells from human donors at U. Chicago, aiming to restore the body's ability to control blood sugar. ^{1 2 3 5 6}

Who Is on the Research Team?

Piotr Witkowski, MD PhD

Principal Investigator

University of Chicago

Are You a Good Fit for This Trial?

This trial is for adults aged 18-70 with Type 1 Diabetes (T1D) diagnosed before age 40, insulin-dependent for at least 5 years, and have a history of severe or problematic hypoglycemia despite intensive diabetes management. Participants must not be overweight, pregnant, or planning pregnancy soon. They should also not have certain blood or immune conditions.

Inclusion Criteria

I was diagnosed with Type 1 Diabetes before 40, need insulin for over 5 years, and have had severe low blood sugar.

I check my glucose 3+ times daily and use insulin injections or a pump under a specialist's care.

You have a history of not being able to sense when your blood sugar is low or high, or having big swings in blood sugar levels despite taking medicine for diabetes.

Exclusion Criteria

I have high levels of certain antibodies against transplant tissues.

Your kidney function is below a certain level.

You have had a high level of protein in your urine in the past.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Islet Transplantation

Participants receive islet cells from cadaver donors via vein to assess safety and control of blood sugar

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after transplantation, with a focus on maintaining HbAlc <7.0% and absence of severe hypoglycemic events

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 donors into patients' livers to manage blood sugar levels in T1D without daily insulin shots. The goal is to achieve better control over blood glucose with these transplanted cells that produce insulin.

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

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]

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]

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]

Recent advancements in islet retrieval techniques have improved the number and purity of islets available for transplantation, allowing for renewed clinical trials in type 1 diabetes patients.

Islet transplantation, while having a lower success rate for insulin independence compared to whole pancreas transplantation, offers several advantages such as being a simpler and safer outpatient procedure, potential for cell banking, and future possibilities for xenotransplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Islet transplantation. Inoue, K., Miyamoto, M.[2019]

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]

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]

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 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 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]

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]

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]

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]

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]

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/74/7/1068/158190/Advances-in-Cell-Replacement-Therapies-for

Advances in Cell Replacement Therapies for Diabetes In the largest multicenter trials of ITA and IAK in the U.S., insulin independence was additionally achieved in 74% of islet transplant ...

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.