Islet Cell Transplant for Type 1 Diabetes

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Northwestern University

Must be taking: Immunosuppressants

Must not be taking: Corticosteroids, Anticoagulants

Disqualifiers: Obesity, High HbA1c, Kidney disease, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a treatment for type 1 diabetes involving the transplant of insulin-producing cells and a drug that helps the body accept these cells by calming the immune system. It targets patients who have dangerous low blood sugar levels that they can't detect. The new cells help control blood sugar.

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

The trial does not specify if you need to stop your current medications, but it involves taking immunosuppressive medications. It's best to discuss your current medications with the trial team to understand any potential interactions.

What data supports the effectiveness of the islet cell transplant treatment for type 1 diabetes?

Islet cell transplantation has shown promising results, with some centers reporting that 80% of patients achieve insulin independence after one year. Additionally, it improves blood sugar control and reduces the risk of severe low blood sugar episodes. ^{1 2 3 4 5}

What is known about the safety of islet cell transplantation for type 1 diabetes?

Islet cell transplantation can have some serious side effects, including bleeding, infections, and issues related to the immune system. Some patients experienced elevated liver enzymes, bleeding in the abdomen, and decreased kidney function, but these issues were resolved without lasting problems. Long-term risks like cancer and serious infections are rare, but minor issues like mouth ulcers and diarrhea can occur due to the medications used to prevent rejection of the transplant. ^{6 7 8 9 10}

How does islet cell transplant treatment differ from other treatments for type 1 diabetes?

Islet cell transplant is unique because it involves transplanting insulin-producing cells into the body, aiming to achieve insulin independence, unlike traditional treatments that rely on external insulin injections. This procedure is less invasive than whole pancreas transplants and offers the potential to reduce or eliminate the need for lifelong immunosuppressive drugs. ^{1 11 12 13 14}

Research Team

Daniel Borja-Cacho, MD

Principal Investigator

Northwestern University

Eligibility Criteria

This trial is for adults aged 18-65 with Type 1 Diabetes, specifically those who've had severe hypoglycemia and aren't aware when their blood sugar gets too low. They should have been insulin-dependent for at least 5 years, mentally stable, and under a doctor's care for diabetes management for over a year. People with obesity, high insulin needs, certain infections or diseases, pregnancy or breastfeeding women, and those not using contraception are excluded.

Inclusion Criteria

Ability to provide written informed consent

You have had type 1 diabetes and required insulin for at least 5 years, and meet specific medical criteria including low c-peptide levels, severe hypoglycemia, reduced awareness of hypoglycemia, or previous islet cell transplant with continued need for insulin and immunosuppression medication.

You had a very low blood sugar episode at least once in the past year.

Exclusion Criteria

I have painful gallstones.

I have stomach or intestine problems that affect how I absorb pills.

You have high levels of protein in your urine.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Islet Cell Transplantation

Participants receive islet cell transplantation under alemtuzumab induction

Varies based on donor availability

Multiple visits for transplantation and monitoring

Post-Transplant Monitoring

Participants are monitored for safety and efficacy of the islet transplantation

2 years

Regular follow-up visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years after the final islet transplant

Treatment Details

Interventions

• Islet Cell Transplant

Trial Overview The study tests the safety and effectiveness of transplanting islet cells into patients with Type 1 Diabetes who often have dangerously low blood sugar without realizing it. It includes immunosuppressive drugs to prevent rejection of the transplanted cells.

Participant Groups

Group I: Islet Cell Transplant Experimental Treatment 1 Intervention

All qualified subjects will be put on United Network for Organ Sharing (UNOS) Islet Transplant wait list for potential islet cell transplant.

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

Findings from Research

Islet transplantation shows promise as a curative treatment for type 1 diabetes, with some centers reporting insulin independence rates of over 80% after one year, although these results are limited to experienced centers and small patient cohorts.

Major challenges remain, including the risk of immune rejection, the need for strong immunosuppression, and the high loss of islet viability post-transplant, highlighting the need for improvements in islet isolation techniques and alternative tissue sources.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pancreatic islet transplantation, results, techniques, perspectives and indications]. Benhamou, PY., Bayle, F.[2022]

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]

Clinical pancreatic transplantation for Type 1 diabetes has shown improved outcomes, with some centers reporting over 70% graft survival rates after one year.

Successful pancreatic transplants can lead to normalization of glucose tolerance in 60-65% of patients and may also provide curative effects on complications associated with Type 1 diabetes, such as diabetic retinopathy and nephropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Status of pancreatic organ and pancreatic islet cell transplantation]. Land, W.[2019]

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]

Islet transplantation is a promising alternative treatment for type 1 diabetes, which affects an estimated 300,000 to 500,000 people in the U.S., potentially improving health outcomes compared to traditional insulin therapy.

The North American Collaborative Islet Transplant Registry (CITR) is collecting and analyzing data from islet transplants across North America to enhance the safety and efficacy of these procedures, with participation from over 22 transplant centers to identify key factors influencing patient and graft survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NIH-Supported National Islet Transplantation Registry. Close, N., Anand, R., Hering, B., 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]

References

1. France pubmed.ncbi.nlm.nih.gov

[Pancreatic islet transplantation, results, techniques, perspectives and indications]. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Progress in islet transplantation in patients with type 1 diabetes mellitus. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

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

4. Japan pubmed.ncbi.nlm.nih.gov

Pancreatic islet transplantation: toward definitive treatment for diabetes mellitus. [2020]

5. Germany pubmed.ncbi.nlm.nih.gov

[Status of pancreatic organ and pancreatic islet cell transplantation]. [2019]

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

Risks and side effects of islet transplantation. [2019]

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

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

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

NIH-Supported National Islet Transplantation Registry. [2019]

10. Japan pubmed.ncbi.nlm.nih.gov

Current state and future evolution of pancreatic islet transplantation. [2023]

11. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Prospective and challenges of islet transplantation for the therapy of autoimmune diabetes. [2006]

13. Germany pubmed.ncbi.nlm.nih.gov

Islet cell transplantation in diabetes mellitus--from bench to bedside. [2005]

14. England pubmed.ncbi.nlm.nih.gov

Islet cell transplantation. [2023]