Islet Transplantation for Type 1 Diabetes

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must be taking: Insulin

Must not be taking: Glucocorticoids, Antipsychotics, Antidepressants, others

Disqualifiers: Liver disease, Cardiovascular disease, Infection, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method for managing difficult-to-control type 1 diabetes by transplanting islet cells. These special cells produce insulin, which controls blood sugar levels. The study aims to determine if this method is safe and can stabilize blood sugar in individuals experiencing frequent swings and low levels, despite proper insulin use. Suitable candidates have had type 1 diabetes for over five years and frequently experience low blood sugar episodes that disrupt their lives. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

Will I have to stop taking my current medications?

The trial requires that you do not take certain medications that could affect blood sugar control, such as glucocorticoids and some psychiatric medications. If you are on any of these, you may need to stop them to participate.

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

Research has shown that islet cell transplantation is generally safe for people with Type 1 diabetes. Studies have found that this treatment can effectively control blood sugar levels over time. Evidence indicates that islet transplantation, even when combined with medications to prevent rejection, is well-tolerated. Serious complications or unexpected side effects are uncommon.

Regarding long-term safety, one study found that 92% of patients lived for more than 13 years after the procedure. While any medical procedure carries risks, the data suggests that islet transplantation is a promising option for those with difficult-to-control diabetes. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for Type 1 Diabetes, which often involve daily insulin injections or insulin pumps, islet cell transplantation offers a unique approach by directly replacing the insulin-producing cells that the body is missing. This method has the potential to restore the body's ability to regulate blood sugar naturally, reducing or possibly eliminating the need for external insulin. Researchers are excited about this treatment because it addresses the root cause of the disease rather than just managing symptoms. Additionally, when combined with immunosuppression, it may improve the longevity and effectiveness of the transplanted cells, offering a more sustainable solution for patients.

What evidence suggests that islet cell transplantation could be an effective treatment for difficult to control type 1 diabetes?

Research has shown that islet cell transplantation, which participants in this trial may receive, can help manage difficult-to-control type 1 diabetes. Studies have found that this treatment improves blood sugar levels and reduces episodes of low blood sugar. In one study, 74% of patients no longer needed insulin shots after the procedure. Long-term data indicates that the transplanted cells can last for years, with about 86% surviving at least one year. This suggests that islet cell transplantation offers a promising option for better diabetes management. ^{2 4 6 7 8}

Who Is on the Research Team?

Fouad Kandeel, MD

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with difficult to control Type 1 diabetes, experiencing severe blood sugar fluctuations despite using insulin and monitoring. Candidates must have had diabetes for at least 5 years, no chronic kidney or liver disease, and be able to follow a strict post-transplant regimen. Exclusions include significant heart disease, certain immune responses (high antibody levels), obesity (BMI over 30), active infections, substance abuse, psychiatric issues affecting treatment adherence, and any history of cancer except specific skin or cervical cancers.

Inclusion Criteria

Ability to give informed consent

My liver is healthy.

I have had Type 1 diabetes for over 5 years and it's hard to control.

Exclusion Criteria

You have a high body mass index (BMI).

I am on long-term medication for a chronic illness.

I currently have an ongoing infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Islet Cell Transplantation

Participants undergo islet cell transplantation to evaluate safety and effectiveness in controlling type 1 diabetes

Not specified

Immunosuppressive Treatment

Participants receive a glucocorticoid-free immunosuppressive regimen to prevent rejection of transplanted islets

Not specified

Follow-up

Participants are monitored for safety and effectiveness after transplantation

20 months

What Are the Treatments Tested in This Trial?

Interventions

• Islet cell transplantation
• Islet Transplantation + Immunosuppression

Trial Overview The study tests the safety and effectiveness of islet cell transplantation without steroids in managing Type 1 diabetes that's hard to control with standard treatments. It involves transplanting cells into patients who then receive an immunosuppressive drug regimen to prevent rejection of the new cells while avoiding glucocorticoids which can affect blood sugar levels.

How Is the Trial Designed?

Group I: 1 Experimental Treatment 2 Interventions

Islet cell transplantation alone

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

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]

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]

Pancreatic islet transplantation (IT) can improve glycaemic control and reduce the fear of hypoglycaemia for individuals with complex Type 1 diabetes, with benefits observed up to 36 months post-transplant.

However, the overall impact on quality of life (QoL) is unclear due to mixed results from studies, limited sample sizes, and the lack of sensitivity in some patient-reported outcome measures, indicating a need for more comprehensive assessments of patient satisfaction and QoL post-transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes following islet cell or pancreas transplantation (alone or after kidney) in Type 1 diabetes: a systematic review. Speight, J., Reaney, MD., Woodcock, AJ., et al.[2021]

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. 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. 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.

4. diabetesjournals.org diabetesjournals.org/diabetes/article/74/7/1068/158190/Advances-in-Cell-Replacement-Therapies-for

Advances in Cell Replacement Therapies for Diabetes In the largest multicenter trials of ITA and IAK in the U.S., insulin independence was additionally achieved in 74% of islet transplant ...

5. amjtransplant.org amjtransplant.org/article/S1600-6135(22)27532-7/fulltext

Islet Cell Transplantation in Type 1 Diabetes: An Analysis ... For patients with three islet transplants, the graft survival at 1, 2 and 3 years were 87%, 69% and 62%, respectively. In the combined sample (including all ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10758748/

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. clinicaltrials.gov clinicaltrials.gov/study/NCT00566813

NCT00566813 | Islet Transplantation in Type 1 Diabetic ... The primary purpose of this study is to demonstrate the safety of allogeneic islet transplantation in type 1 diabetic patients performed at the University ...