Islet Transplant for Type 1 Diabetes

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Rodolfo Alejandro

Disqualifiers: Malignancy, HIV, Active infections, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1 year

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether transplanting islet cells (clusters of insulin-producing cells) can help people with Type 1 Diabetes manage their blood sugar without insulin shots. It also examines the reduction of serious low blood sugar episodes and assesses if the transplant can prevent diabetes-related complications. Some participants will receive additional treatments to protect the new cells. Suitable candidates have had Type 1 Diabetes for over five years and struggle with very low blood sugar or have difficulty controlling their diabetes despite significant efforts. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to important advancements in diabetes care.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, since the trial involves islet cell transplantation and medications like infliximab, etanercept, and exenatide, it's possible that some medication adjustments might be needed. Please consult with the trial coordinators for specific guidance.

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

Research has shown that islet transplantation is generally safe for people with Type 1 diabetes. Studies have found that this treatment does not cause serious side effects. For example, one study reported no negative effects directly linked to the islet transplantation itself, indicating patients handled the treatment well.

Another study found that islet transplantation can help maintain stable blood sugar levels for many years. This stability is crucial because it can prevent other health problems related to diabetes.

Overall, evidence supports islet transplantation as a safe option for managing Type 1 diabetes. It has been tested in other studies, showing positive results and a good safety record. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Type 1 Diabetes?

Islet transplantation is unique because it involves transplanting insulin-producing islet cells into people with Type 1 diabetes, potentially restoring their ability to produce insulin naturally. Unlike standard treatments that rely on external insulin administration, like injections or pumps, this approach aims to address the root cause of insulin deficiency. Researchers are excited about this treatment because it offers the possibility of reducing or even eliminating the need for daily insulin therapy, which can significantly improve quality of life for patients.

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

Research shows that islet transplantation, which participants in this trial will receive, can be a promising treatment for people with Type 1 Diabetes. It helps improve blood sugar control and reduces the need for insulin shots. Studies have shown that some patients achieved better blood sugar levels and required less insulin after the transplant. Over time, about half of the patients maintained these benefits. The treatment has generally been safe, with most patients living well for several years. Overall, islet transplantation offers hope for better diabetes management and fewer complications. ^{1 5 6 7 8}

Who Is on the Research Team?

Camillo Ricordi, M.D.

Principal Investigator

University of Miami, Diabetes Research Institute

Rodolfo Alejandro, M.D.

Principal Investigator

University of Miami, Diabetes Research Institute

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with Type 1 Diabetes Mellitus, BMI ≤26, experiencing severe hypoglycemia unawareness or poor diabetes control despite intensive insulin therapy. Candidates must have had diabetes for over 5 years and show progressive complications. Excluded are those with certain blood markers, untreated eye issues, kidney dysfunction, high insulin requirements or lipid levels, specific infections including HIV/HCV/EBV, history of malignancy (except some skin cancers), unstable heart conditions, pregnancy/breastfeeding without proper contraception use, recent substance abuse/smoking.

Inclusion Criteria

My type 1 diabetes is getting worse.

One or more of the following:

- Body Mass Index (BMI) ≤26

Exclusion Criteria

C-peptide > 0.3ng/ml basal or stimulated

I am a woman who can have children and am using an approved birth control method.

Alcohol abuse, substance abuse or smoking within the previous 6 months

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Transplantation

Participants receive intraportal islet cell infusion from one or more donors

Peri-transplant period

Treatment

Participants receive immunosuppressive therapy including Daclizumab, Sirolimus, Tacrolimus, and potentially Infliximab or Etanercept

1 year

Follow-up

Participants are monitored for safety, islet graft function, and metabolic control

1 year

What Are the Treatments Tested in This Trial?

Interventions

• islets

Trial Overview The study tests whether transplanting islet cells can reverse the need for insulin in Type 1 Diabetes patients while avoiding steroid-based immunosuppression. It also examines if this procedure prevents severe low blood sugar episodes and improves long-term health outcomes related to diabetes complications. The effects of infliximab and etanercept on early islet survival and exenatide on graft function/survival are being studied as well.

How Is the Trial Designed?

Group I: Islet transplantation Experimental Treatment 1 Intervention

Subjects receiving intraportal Islet cell infusion (transplant)

Who Is Running the Clinical Trial?

Rodolfo Alejandro

Lead Sponsor

Trials

10

Recruited

210+

Health Resources and Services Administration (HRSA)

Collaborator

Trials

88

Recruited

152,000+

National Center for Research Resources (NCRR)

Collaborator

Trials

540

Recruited

317,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

University of Miami

Collaborator

Trials

976

Recruited

423,000+

Diabetes Research Institute Foundation

Collaborator

Trials

10

Recruited

80+

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]

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 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 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 A recent phase 3 study confirmed that allogeneic islet transplantation is a safe and effective treatment for patients with T1D and unstable ...

2. 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 ...

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 ... Overall survival was 92% (73 of 79) over a median follow-up of 13·1 years, with a 20-year survival probability of 84%. Adverse events related to ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9889686/

Pancreatic islet transplantation in type 1 diabetes: Current ... The median time of graft survival was 5.9 years. Glycemic control was significantly improved after islet transplantation. Near half of the patients maintained ...

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. 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 ...

8. 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.