Islet Transplantation for Type 1 Diabetes

Recruiting at 1 trial location

Overseen By Midhat Abdulreda, Ph.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Trial Phase: Phase 1 & 2

Sponsor: Midhat H. Abdulreda

Must not be taking: Topical steroids, Immune-modulatory drugs

Disqualifiers: Glaucoma, HbA1c >10%, Hypertension, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

2 Participants Needed

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 transplanting insulin-producing cells into the eye. The goal is to determine if this method can manage the condition more effectively. Participants must have diabetes requiring insulin, stable kidney function, and one eye with very limited vision. The trial involves a brief procedure where these cells are infused into the eye to potentially improve blood sugar control. 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 therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on systemic steroids, you may need to adjust your dosage to 5 mg of prednisone daily or an equivalent dose for physiological replacement only.

What prior data suggests that intraocular islet transplantation is safe for humans?

Research has shown that transplanting human pancreatic islets may help treat type 1 diabetes. Studies have examined the safety and tolerability of this treatment. For instance, some research found that patients who received islet transplants could reduce or even stop using insulin, indicating improved blood sugar control.

Regarding safety, these studies generally find that islet transplantation is well-tolerated. However, like any medical procedure, there are risks. Some individuals might experience mild side effects, but serious complications are rare. It is important to note that this treatment is still under investigation and is not yet a standard option for everyone with type 1 diabetes. Prospective trial participants can use this information to understand what other patients have experienced. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard insulin therapy and glucose monitoring for Type 1 Diabetes, human pancreatic islet transplantation offers a groundbreaking approach by placing insulin-producing cells into the eye's anterior chamber. This method is unique because it allows the transplanted islets to be easily monitored and maintained, potentially leading to better long-term management and reduced need for regular insulin shots. Researchers are excited because this approach could offer a more natural regulation of blood sugar levels, mimicking the body's own insulin production more closely than current methods.

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

Research has shown that transplanting human pancreatic islet cells can help people with type 1 diabetes. This trial will examine the effects of Human Pancreatic Islet Transplantation, which can improve blood sugar control and enable some patients to produce their own insulin again. In one study, the transplanted cells survived in about 86% of patients for one year and in 65% for five years. Another study found that the average survival time for these cells was about 5.9 years. Overall, these findings suggest that this treatment can offer long-term benefits, although not every transplant lasts that long. ^{1 2 6 7 8}

Who Is on the Research Team?

Midhat Abdulreda, Ph.D.

Principal Investigator

University of Miami

Are You a Good Fit for This Trial?

This trial is for individuals with Type 1 Diabetes who have severe vision loss in at least one eye and are legally blind. They must have a normal cornea, stable intraocular lens if applicable, and no response to a mixed meal tolerance test. People can't join if they've had certain immune reactions, uveitis, narrow iris angle, recent investigational drug use, history of most cancers or substance abuse.

Inclusion Criteria

Have you received a legal blindness diagnosis in one or both eyes?

Patient with at least one eye with extensive loss of vision from hand motion to no light perception

Have stable lens in blind eye (natural lens or replaced in previous cataract surgery)

Exclusion Criteria

You have not taken any experimental drugs in the past 4 weeks.

I have had cancer before, but it was completely removed except for skin cancer.

You currently have a problem with drinking alcohol or using drugs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Intraocular islet transplantation into the anterior chamber of the eye with localized maintenance immunosuppression via topical application of eye-drops

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including absence of ocular complications and confirmation of intraocular islet graft survival

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Human Pancreatic Islet Transplantation

Trial Overview

The study tests transplanting human pancreatic islet cells into the eye's anterior chamber to help manage diabetes in those with low vision. The procedure involves placing cells through the cornea and requires patients to lie flat afterwards to ensure cell attachment.

How Is the Trial Designed?

Group I: Human Pancreatic Islet Transplantation Experimental Treatment 1 Intervention

Islet transplantation into the anterior chamber of the eye single arm

Human Pancreatic Islet Transplantation is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Islet Transplantation for:

• Type 1 Diabetes

Approved in Canada as Islet Transplantation for:

• Type 1 Diabetes

Approved in European Union as Islet Transplantation for:

• Type 1 Diabetes

Who Is Running the Clinical Trial?

Midhat H. Abdulreda

Lead Sponsor

Trials

1

Recruited

2+

Bascom Palmer Eye Institute

Collaborator

Trials

12

Recruited

1,200+

Diabetes Research Institute Foundation

Collaborator

Trials

10

Recruited

80+

Published Research Related to This Trial

Pancreatic islet transplantation is a viable treatment for patients with type 1 diabetes mellitus, offering a potential solution for managing the disease.

The procedure has been successfully performed in various countries, indicating its global acceptance and application in diabetes care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Islet Transplantation Covered by Health Insurance in Japan. Noguchi, H.[2022]

Pancreatic islet transplantation (IT) can significantly improve the quality of life for individuals with type 1 diabetes by reducing severe hypoglycemic episodes and improving glycemic control, as reported by most recipients in a study of 16 adults.

Despite the need for ongoing immunosuppression and the stress of being on the waiting list, recipients expressed overall satisfaction with the transplant process and outcomes, indicating that their expectations were largely met, though some still hoped for complete insulin independence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Well, I Wouldn't be Any Worse Off, Would I, Than I am Now? A Qualitative Study of Decision-Making, Hopes, and Realities of Adults With Type 1 Diabetes Undergoing Islet Cell Transplantation. Speight, J., Woodcock, AJ., Reaney, MD., et al.[2022]

Pancreas transplantation is considered a safe and moderately successful treatment for patients with severe diabetic complications, outweighing the risks of long-term immunosuppression.

In contrast, islet transplantation has not achieved similar success rates, indicating that it remains a challenging procedure compared to whole pancreas transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical pancreas and islet transplantation. Part 1: registry statistics and an overview. Sutherland, DE.[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]

In a study of 325 adult recipients of islet transplants, 23% achieved insulin independence for at least 2 weeks three years after their first infusion, indicating that islet transplantation can significantly improve metabolic control in Type 1 diabetes.

The use of immunosuppressive protocols with daclizumab or etanercept was associated with higher rates of insulin independence and lower rates of function loss, suggesting that these approaches enhance the efficacy of islet transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

2008 Update from the Collaborative Islet Transplant Registry. Alejandro, R., Barton, FB., Hering, BJ., et al.[2022]

The study demonstrated that encapsulating pancreatic islets in alginate-chitosan-PEG provides immunoprotection by reducing IL-2 secretion from lymphocytes, which is crucial for preventing immune rejection in transplantation.

Insulin secretion from the encapsulated islets was effectively stimulated by glucose, showing that the encapsulation and PEGylation processes did not negatively impact the islets' ability to respond to glucose, maintaining their functionality similar to non-coated islets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Normal Insulin Secretion from Immune-Protected Islets of Langerhans by PEGylation and Encapsulation in the Alginate-Chitosan-PEG. Najafikhah, N., Hashemi-Najafabadi, S., Zahediasl, S., et al.[2022]

Islet transplantation shows promise as a treatment for type 1 diabetes, offering advantages over whole pancreas transplantation, particularly for patients with kidney failure.

Out of 32 pancreases sent for islet isolation, only 19 yielded viable islets, and only 4 (18%) were deemed optimal for implantation, highlighting challenges in donor selection and laboratory techniques that need to be addressed for improved success rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pancreas donation for islet transplantation. Frutos, MA., Ruiz, P., Mansilla, JJ.[2013]

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 cell transplantation faces significant challenges, including insufficient yield from donor pancreases and high islet cell loss during purification, limiting its effectiveness for treating insulin-deficient diabetes.

Current islet transplants are highly susceptible to rejection and often fail shortly after transplantation, necessitating advancements in histocompatibility matching and immunosuppression techniques before they can be widely applied in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Replacement of pancreatic beta cells as treatment for diabetes mellitus: a review. Jonasson, O., Hoversten, GH.[2021]

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]

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]

In a study of 44 patients with Type 1 Diabetes who underwent islet transplantation, a larger islet infusion volume was negatively associated with graft survival, suggesting that smaller infusion volumes may be more effective when combined with improved immunosuppressive protocols.

The administration of Exenatide and Filgrastim was positively associated with better graft survival, indicating that these treatments could enhance the success of islet transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

G-CSF and Exenatide Might Be Associated with Increased Long-Term Survival of Allogeneic Pancreatic Islet Grafts. Zoso, A., Serafini, P., Lanzoni, G., et al.[2020]

Whole pancreas transplantation has been successfully performed for over 30 years, leading to significant health benefits such as improved quality of life and reduced complications from diabetes, including retinopathy and nephropathy.

Islet transplantation has also shown promise, but more research is needed to confirm its long-term benefits, and there is a critical need for alternative sources of beta cells due to the limited availability of pancreas donations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on transplanting beta cells for reversing type 1 diabetes. Robertson, RP.[2019]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/35588757/

Pancreatic islet transplantation in type 1 diabetes - PubMed

Median graft survival was 5·9 years (IQR 3·0-9·5), and graft failure occurred in 91 (36%) patients. 178 (70%) recipients had sustained graft ...

2.

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 ...

3.

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 ...

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.

frontiersin.org

frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1391504/full

Pancreatic islet transplantation: current advances and ...

This clinical trial suggests that islet transplantation using the Edmonton protocol can restore long-term endogenous insulin production and stabilize blood ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11180903/

Pancreatic islet transplantation: current advances and ...

In recent years, advances in islet transplantation have significantly advanced the treatment of diabetes, allowing patients to discontinue exogenous insulin 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/NCT06239636

NCT06239636 | First-in-human Safety Study of ...

The study is an open, one-armed study where adult subjects with longstanding type 1 diabetes will receive transplantation of Langerhans islet cells (25 000 000- ...