Islet Cell Transplant for Type 1 Diabetes

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Chicago

Must be taking: Exogenous insulin

Disqualifiers: Organ transplant, Portal hypertension, Malignancy, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for individuals with type 1 diabetes, particularly those who struggle to control their blood sugar despite intensive management. The main goal is to determine if transplanting insulin-producing islet cells (allogenic islet cell transplantation) can safely manage blood sugar levels and reduce severe low blood sugar episodes. Participants should have had type 1 diabetes for over five years, rely on frequent insulin injections, and have experienced issues like severe blood sugar swings or unawareness of low blood sugar. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications. However, since it involves transplant and anti-rejection drugs, it's possible that medication adjustments might be needed. Please discuss with the trial team for specific guidance.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that islet cell transplantation has been tested for safety in people with type 1 diabetes. One study found that this treatment can help achieve nearly normal blood sugar levels and reduce severe low blood sugar episodes. Another review noted that most patients handled the procedure well, although challenges with the transplant itself remain.

The "Edmonton Protocol" uses specific drugs to prevent the body from rejecting the transplant without steroids. Researchers tested this approach on 36 people with type 1 diabetes who had severe low blood sugar symptoms, and the results showed positive safety outcomes.

Overall, while risks exist, these studies suggest that islet cell transplantation is relatively safe for humans with careful monitoring and management. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about allogenic islet cell transplantation for type 1 diabetes because it offers a unique approach by directly replacing the insulin-producing cells that are damaged in this condition. Unlike standard treatments, which primarily focus on managing blood sugar levels with insulin injections or pumps, this therapy aims to restore the body's natural ability to produce insulin. By potentially reducing or even eliminating the need for external insulin, it could significantly improve the quality of life for patients and reduce the long-term complications associated with diabetes.

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

Research has shown that transplanting islet cells from a donor can help people with type 1 diabetes better control their blood sugar. In this trial, participants will receive an allogenic islet cell transplantation. In previous studies, some patients stopped using insulin within 75 days and maintained healthy blood sugar levels for a year. This treatment not only improves long-term blood sugar control but also helps prevent dangerous low blood sugar episodes. Over time, islet cell transplants have provided lasting benefits, with many patients maintaining transplanted cell function for several years. While not everyone can stop using insulin completely, many find it much easier to manage their diabetes. ^{1 2 6 7 8}

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 people aged 18-58 with type 1 diabetes who have been diabetic for at least five years. They must be on a strict regimen of glucose monitoring and insulin injections, experience severe diabetes complications or hypoglycemic unawareness, and can give informed consent. Excluded are those with recent heart attacks, certain liver issues, obesity (BMI > 28), prior transplants, infections, substance abuse problems, pregnancy or inability to use contraception.

Inclusion Criteria

I have unstable diabetes, don't feel when my blood sugar is low, or my diabetes is getting worse.

I have been diabetic for 5 years or more.

I check my blood sugar and inject insulin at least three times a day under a doctor's care.

Exclusion Criteria

Pregnancy, or inability to comply with contraceptive regimen

Failure to meet inclusion criteria

Serologic positivity for HIV and/or hepatitis

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Transplantation

Participants receive allogenic islet cells via intraportal infusion and begin immunosuppressive therapy

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after transplantation, focusing on hyperglycemia control and hypoglycemia reversal

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Allogenic Islet Cell Transplantation

Trial Overview

The study tests the safety and initial effectiveness of transplanting human islet cells into patients with type 1 diabetes to control blood sugar levels. It follows the 'Edmonton Protocol' which uses specific anti-rejection drugs without steroids during transplantation.

How Is the Trial Designed?

Group I: Transplant Experimental Treatment 2 Interventions

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Published Research Related to This Trial

Co-transplanting mesenchymal stromal cells (MSCs) with islets significantly improved glucose control in a mouse model of diabetes, particularly when islets were placed under the kidney capsule, indicating a potential strategy to enhance islet transplant outcomes.

The MSCs reduced early islet cell death (apoptosis) and improved islet survival, suggesting that MSCs may provide protective effects during the critical early post-transplant period, although they did not increase beta cell proliferation or differentiate into beta cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mesenchymal stromal cells improve transplanted islet survival and islet function in a syngeneic mouse model. Borg, DJ., Weigelt, M., Wilhelm, C., et al.[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]

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]

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]

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]

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 transplantation has become a viable treatment for type 1 diabetes, significantly reducing severe hypoglycemia in about 15% of patients, with recent improvements in long-term outcomes now comparable to pancreas transplantation.

The procedure is gaining wider acceptance, with reimbursement from health insurance providers in several countries, and ongoing efforts aim to enhance its availability and safety, potentially allowing for earlier intervention in newly diagnosed patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

State of the art of clinical islet transplantation and novel protocols of immunosuppression. Shapiro, AM.[2021]

Citations

1.

pmc.ncbi.nlm.nih.gov

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

The Current Status of Allogenic Islet Cell Transplantation

Overall, these recent studies and clinical data results support the safety and efficacy of islet cell transplantation for the treatment of T1D ...

2.

pmc.ncbi.nlm.nih.gov

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

Islet Cell Replacement and Regeneration for Type 1 Diabetes

Remarkably, the patient achieved insulin independence within 75 days and sustained over 98% time-in-range glycemic control for a year, with ...

3.

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 ...

4.

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 ...

5.

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.

6.

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 ...

7.

thelancet.com

thelancet.com/journals/eclinm/article/PIIS2589-5370(23)00510-2/fulltext

Islet transplantation outcomes in type 1 diabetes and ...

Evidence suggests that islet transplantation is an efficacious therapy for selected patients with Type 1 diabetes with proven safety and ...

8.

diabetesjournals.org

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

Advances in Cell Replacement Therapies for Diabetes

The International Trial of the Edmonton Protocol for Islet Transplantation demonstrated in 36 individuals with T1D and severe hypoglycemia that ...