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

17 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The purpose of this study is to evaluate the safety and effectiveness of islet cell transplantation alone (ITA) in patients with difficult to control type I diabetes. Difficult to control type 1 diabetes is defined as wide swings in blood glucose that disrupt the patient's life and result in frequent episodes of low blood glucose despite the proper use of standard insulin therapy and frequent blood glucose monitoring.

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.

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

Islet transplantation is unique because it involves transplanting insulin-producing cells directly into the liver, which can help maintain normal blood sugar levels without the need for daily insulin injections. Unlike traditional treatments, it requires immunosuppressive drugs to prevent rejection, but it offers the potential for insulin independence and fewer hypoglycemic episodes. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment Islet Transplantation + Immunosuppression for Type 1 Diabetes?

Islet transplantation has shown promising results, with some centers reporting that over 80% of patients achieve insulin independence after one year. This success is attributed to improved immunosuppressive protocols and increased islet mass delivered to patients. ^{2 3 4 5 6}

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]

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]

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]

Citations

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

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

2. Denmark pubmed.ncbi.nlm.nih.gov

Safety and tolerability of the T-cell depletion protocol coupled with anakinra and etanercept for clinical islet cell transplantation. [2021]

3. England 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. [2021]

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

Islet alone versus islet after kidney transplantation: metabolic outcomes and islet graft survival. [2022]

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

C-C Chemokine Receptor Type 2-Dependent Migration of Myeloid-Derived Suppressor Cells in Protection of Islet Transplants. [2018]

6. Italy pubmed.ncbi.nlm.nih.gov

Pancreatic islet and stem cell transplantation: new strategies in cell therapy of diabetes mellitus. [2007]