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

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The purpose of this study is to determine the safety of transplanting human islet cells for controlling hyperglycemia in brittle and/or complex patients with type 1 diabetes. In addition, initial observations will be made with regards to the effectiveness of reversing hypoglycemia with this treatment. The "Edmonton Protocol" of using specific anti-rejection drugs without steroids is also being evaluated.

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 islet cell transplantation safe for humans?

Islet cell transplantation can have serious side effects, including liver problems, bleeding, infections, and kidney issues, mostly related to the transplant procedure and the drugs used to prevent rejection. However, these side effects were resolved without lasting harm, and no cancers or deaths were reported in the study. ^{1 2 3 4 5}

How is the islet cell transplant treatment different from other treatments for type 1 diabetes?

Islet cell transplantation is unique because it involves transplanting insulin-producing cells from a donor to help manage blood sugar levels in people with type 1 diabetes, potentially reducing the need for insulin injections. Unlike other treatments, it is minimally invasive and specifically targets severe cases of hypoglycemia and insulin dependence, but it requires immunosuppressive therapy to prevent rejection of the transplanted cells. ^{2 4 6 7 8}

What data supports the effectiveness of the treatment Allogenic Islet Cell Transplantation for Type 1 Diabetes?

Allogenic islet cell transplantation has been shown to help control severe low blood sugar and reduce the need for insulin in some patients with type 1 diabetes. Recent improvements have increased the long-term success of this treatment, making it more comparable to whole pancreas transplantation in terms of outcomes. ^{2 4 6 9 10}

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]

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]

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]

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]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Ambulatory intravenous insulin and islet cell transplantation to treat severe type III insulin hypersensitivity in a patient with type 1 diabetes mellitus. [2020]

2. Germany pubmed.ncbi.nlm.nih.gov

Mesenchymal stromal cells improve transplanted islet survival and islet function in a syngeneic mouse model. [2021]

3. Italy pubmed.ncbi.nlm.nih.gov

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

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

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

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

Current issues in allogeneic islet transplantation. [2021]

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

Adverse events in clinical islet transplantation: one institutional experience. [2021]

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

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

8. Korea (South) pubmed.ncbi.nlm.nih.gov

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

9. 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]

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

C-C Chemokine Receptor Type 2-Dependent Migration of Myeloid-Derived Suppressor Cells in Protection of Islet Transplants. [2018]