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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for type 1 diabetes by testing the safety and effectiveness of transplanting islet cells, which produce insulin. The study targets individuals with type 1 diabetes who often fail to notice dangerously low blood sugar levels. Participants experiencing severe hypoglycemia and those who struggle to manage it with current treatments may be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

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.

Is there any evidence suggesting that islet cell transplant is likely to be safe for humans?

Research has shown that islet cell transplantation is a safe option for people with Type 1 diabetes. One study found this procedure safe and effective for patients with unstable diabetes. Another study, which tracked patients for 10 years, found it helped control blood sugar levels and reduced severe low blood sugar episodes over time. Evidence also suggests that this treatment is safe for certain patients, showing good results without major safety concerns. Overall, past studies have indicated that this treatment is well-tolerated. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Islet cell transplant is unique because it offers a potential cure for Type 1 Diabetes by directly replacing the insulin-producing cells that the disease destroys. Unlike standard treatments that manage symptoms with insulin injections or pumps, this transplant aims to restore normal insulin production. Researchers are excited because it could significantly reduce or even eliminate the need for daily insulin therapy, offering patients the possibility of long-term independence from regular insulin administration.

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

Studies have shown that islet cell transplants can greatly improve blood sugar control in people with type 1 diabetes. Many patients no longer need insulin shots and can maintain stable blood sugar levels for at least a year. In one study, 91% of transplant recipients did not experience severe low blood sugar episodes after one year. Long-term research indicates that islet transplants can remain effective for many years, with a 10-year follow-up showing lasting improvements in blood sugar management. These findings suggest that islet cell transplants offer a promising option for those with severe blood sugar issues. ^{1 2 6 7 8}

Who Is on the Research Team?

Daniel Borja-Cacho, MD

Principal Investigator

Northwestern University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

1. 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 ...

2. 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 ...

3. 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 ...

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. sciencedirect.com sciencedirect.com/science/article/pii/S1600613522275327

Islet Cell Transplantation in Type 1 Diabetes: An Analysis ... Ninety-one percent of all recipients were free of severe hypoglycemic episodes at 1 year. Furthermore, the KM survival estimates showed that 91%, 85% and 80% of ...

6. 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 ...

7. 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.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11748148/

Can Islet Transplantation Possibly Reduce Mortality in ... Among T1D subjects, crude all-cause mortality per 1,000 person-years was 8% with 8 years mean follow-up and 2.9% among controls with a mean ...