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

26 Participants Needed

Trial Summary

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.

What data supports the effectiveness of islet transplantation for type 1 diabetes?

Islet transplantation has shown to be effective in reducing severe low blood sugar episodes and improving blood sugar control in people with type 1 diabetes. Some studies report that up to 80% of patients can become insulin-independent for at least one year after the procedure, although long-term effectiveness can vary. ^{1 2 3 4 5}

Is islet transplantation safe for humans?

Islet transplantation for type 1 diabetes has shown some safety concerns, including severe adverse events like elevated liver enzymes, bleeding, infections, and kidney issues, mostly related to the transplant procedure and the drugs used to prevent rejection. However, these events were resolved without lasting effects, and no cases of cancer or death were reported in the study. ^{6 7 8 9 10}

How is islet transplantation different from other treatments for type 1 diabetes?

Islet transplantation is unique because it involves transplanting insulin-producing cells into the body, which can help achieve better blood sugar control without severe low blood sugar episodes, unlike traditional insulin therapy. This minimally invasive procedure offers the potential for insulin independence, although it requires donor cells and lifelong immune system suppression to prevent rejection. ^{1 5 6 10 11}

What is the purpose of this trial?

This trial involves transplanting insulin-producing cells into patients with Type 1 Diabetes to help them manage their blood sugar levels without needing insulin injections. The trial also tests medications to protect these new cells from the immune system and improve their function and survival. One of these medications has been studied for its potential to improve beta-cell function in long-standing type 1 diabetes.

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

Eligibility Criteria

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.

I have had type 1 diabetes for over 5 years.

One or more of the following:

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

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]

References

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

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

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

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

3. England pubmed.ncbi.nlm.nih.gov

Clinical pancreatic islet transplantation. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Pancreatic islet transplantation in type 1 diabetes: 20-year experience from a single-centre cohort in Canada. [2023]

5. France pubmed.ncbi.nlm.nih.gov

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

6. Japan pubmed.ncbi.nlm.nih.gov

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

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

NIH-Supported National Islet Transplantation Registry. [2019]

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

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

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

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

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

Strategic opportunities in clinical islet transplantation. [2019]

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

Clinical islet transplantation. [2019]