Pancreatic Cell Implants for Type 1 Diabetes

(SUGR Trial)

No longer recruiting at 1 trial location

Overseen By Mohammad Razvi

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Seraxis

Must be taking: Immunosuppressants

Must not be taking: Anti-diabetics, Weight loss

Disqualifiers: Type 2 diabetes, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8-12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for individuals with Type 1 diabetes who frequently experience severe low blood sugar. The focus is on the safety and effectiveness of implanting special pancreatic cell clusters (groups of insulin-producing cells) to better manage blood sugar levels. Participants should have had Type 1 diabetes for over five years, experience frequent severe hypoglycemia, and be willing to use a continuous glucose monitor. As a Phase 1 trial, the research aims to understand 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 requires that you have not used any anti-diabetic medications other than insulin in the last 3 months, so you may need to stop those if you are taking them. The protocol does not specify about other medications, so it's best to discuss with the trial team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that treatments like SR-02, which use donor pancreatic cell clusters, have promising safety results. A recent study found that a similar treatment, allogeneic islet transplantation, proved safe and effective for people with type 1 diabetes. This treatment helped some patients better control their blood sugar and reduce their need for insulin.

Another study found that most patients who received similar transplants had a high survival rate and did well over many years. Some side effects occurred, but they were generally manageable. Since allogeneic islet transplantation is already in use, it suggests that SR-02 could be well-tolerated. However, as this study is still in the early stages of testing in humans, more research is needed to confirm its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about allogeneic pancreatic endocrine cell clusters for Type 1 Diabetes because they offer a novel approach by potentially regenerating insulin-producing cells. Unlike the standard treatments, like insulin injections, which manage blood sugar levels but don't address the underlying issue, this method aims to restore the body’s natural ability to produce insulin. This cell-based therapy could significantly reduce the need for frequent insulin administration and improve blood sugar control by directly targeting the root cause of diabetes.

What evidence suggests that this treatment might be an effective treatment for Type 1 diabetes?

Research has shown that donor pancreatic cell implants, such as SR-02, can help manage Type 1 diabetes. Studies have found that these implants can improve blood sugar control and enable some individuals to stop needing insulin. In large studies, about 74% of participants stopped using insulin after receiving similar treatments. Long-term results are encouraging, with many transplants lasting several years. Recent clinical data strongly support the safety and effectiveness of these cell implants. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals with Type 1 diabetes who frequently experience severe low blood sugar episodes. Participants must be willing to undergo immunosuppression therapy to prevent their body from rejecting the treatment.

Inclusion Criteria

I am willing to use a device to monitor my blood sugar levels continuously.

I have been dependent on insulin for 5 or more years.

I frequently experience severe low blood sugar.

Exclusion Criteria

I haven't taken diabetes medication other than insulin in the last 3 months.

I have not taken weight loss medications in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive SR-02 pancreatic endocrine cell clusters implanted in the omentum

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Allogeneic Pancreatic Endocrine Cell Clusters

Trial Overview The study tests the safety and effectiveness of implanting pancreatic endocrine cell clusters into the omentum (a part of the abdomen) in patients with Type 1 diabetes, aiming to find the best dose.

How Is the Trial Designed?

Group I: SR-02 Allogeneic pancreatic endocrine cell clusters Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Seraxis

Lead Sponsor

Trials

1

Recruited

9+

Published Research Related to This Trial

In a study involving four nonimmunosuppressed patients with type 1 diabetes, microencapsulated human islet transplants led to a sustained C-peptide response and significant improvements in blood glucose levels over a 3-year follow-up period.

The encapsulated islet grafts did not trigger an immune response, demonstrating a unique 'bioinvisibility' that allowed for successful function without the need for immunosuppressive therapy, a significant advancement in transplantation for diabetes management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term metabolic and immunological follow-up of nonimmunosuppressed patients with type 1 diabetes treated with microencapsulated islet allografts: four cases. Basta, G., Montanucci, P., Luca, G., et al.[2022]

The study introduces 'Neo-Islets' (NIs), which are islet-sized organoids created by co-culturing islet cells with Mesenchymal Stromal Cells, showing potential to restore normoglycemia in diabetic models without the need for immunosuppression.

In pilot studies, both human and canine NIs demonstrated the ability to re-establish normal blood sugar levels in diabetic mice, indicating that these organoids could significantly expand the donor pool for Type 1 Diabetes treatments and provide a viable alternative to traditional islet transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Significant expansion of the donor pool achieved by utilizing islets of variable quality in the production of allogeneic "Neo-Islets", 3-D organoids of Mesenchymal Stromal and islet cells, a novel immune-isolating biotherapy for Type I Diabetes. Gooch, AM., Chowdhury, SS., Zhang, PM., et al.[2023]

Pancreatic islet transplantation has become a viable treatment option for diabetes, showing significant progress since the initial proof of principle was established.

Current clinical trials are focused on refining recipient selection, improving islet graft production, and managing immunosuppression to enhance the success rates of islet transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Islet transplantation: current status and future directions. Hatipoglu, B., Benedetti, E., Oberholzer, J.[2021]

Pancreatic islet cell transplantation is a feasible procedure, indicating that it can be performed successfully in clinical settings.

However, the current evidence does not support the justification for widespread clinical trials, suggesting that more research is needed to establish its efficacy and safety on a larger scale.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Islet cell transplant not justified. [2016]

Transplanting human fetal pancreas tissue into diabetic and nondiabetic mice resulted in the growth and differentiation of endocrine tissue, leading to the formation of mature islets over a period of up to 37 weeks.

Uncultured fetal pancreas implants grew larger than those that were cultured before transplantation, indicating that the pre-transplant culture period negatively affects the size and viability of the implants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Histologic differentiation of human fetal pancreatic explants transplanted into nude mice. Tuch, BE., Ng, AB., Jones, A., et al.[2019]

Islet transplantation can significantly improve metabolic control in patients with unstable type 1 diabetes, leading to normalization of A1c levels and prevention of severe hypoglycemia, thus enhancing quality of life.

Challenges such as limited islet availability and the need for long-term immunosuppression remain, but ongoing research into islet recovery and immune tolerance strategies shows promise for making this treatment more widely accessible.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transplantation: current developments and future directions; the future of clinical islet transplantation as a cure for diabetes. Hogan, A., Pileggi, A., Ricordi, C.[2019]

Transplanting human embryonic stem cell-derived pancreatic endoderm cells (PECs) into mice successfully corrected diabetes long-term, demonstrating their potential as a limitless source for insulin-producing cells.

This method avoids chronic foreign-body responses and does not require devices or growth factors, allowing PECs to differentiate in vivo and effectively restore glucose regulation in the mice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transplantation of Human Pancreatic Endoderm Cells Reverses Diabetes Post Transplantation in a Prevascularized Subcutaneous Site. Pepper, AR., Pawlick, R., Bruni, A., et al.[2018]

Human Neo-Islets (NIs) have shown the ability to significantly improve glycemic control in a mouse model of Type 1 diabetes, indicating their potential as a curative therapy without the need for anti-rejection drugs.

In a pilot study with insulin-dependent dogs, allogeneic canine NIs improved glycemic control, suggesting that this approach may be effective across species and supports the planned clinical trials for human NIs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraperitoneal administration of human "Neo-Islets", 3-D organoids of mesenchymal stromal and pancreatic islet cells, normalizes blood glucose levels in streptozotocin-diabetic NOD/SCID mice: Significance for clinical trials. Westenfelder, C., Hu, Z., Zhang, P., et al.[2021]

Islet transplantation has shown promise as a treatment for diabetes, with successful autotransplantation in three patients who underwent near-total pancreatectomy, leading to one patient remaining insulin-free and normoglycemic for over 2 years.

While allogeneic islet transplantation in diabetic renal allograft recipients showed some transient islet function, it was generally unsuccessful due to rejection, suggesting that autografts may be more effective in preventing diabetes after extensive pancreatic surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transplantation of dispersed pancreatic islet tissue in humans: autografts and allografts. Sutherland, DE., Matas, AJ., Goetz, FC., et al.[2019]

Allogeneic islet transplantation is recognized as a standard treatment for labile type 1 diabetes in many countries, but the U.S. is facing challenges in its implementation due to regulatory hurdles from the FDA.

The commercialization of islet cell treatments raises ethical and legal concerns, as it may lead to for-profit companies monopolizing a procedure that has been developed through years of academic research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

US food and drug administration (FDA) panel endorses islet cell treatment for type 1 diabetes: A pyrrhic victory? Piemonti, L., Andres, A., Casey, J., et al.[2021]

Xenotransplantation using insulin-producing cells from embryonic pig pancreas (obtained at embryonic day 28) shows promise for long-term engraftment in diabetic rats and rhesus macaques without the need for immune suppression.

Previous transplantation of embryonic pig pancreas appears to induce a state of tolerance to porcine islets, suggesting that this approach could allow for the use of pig islet cells in humans without requiring immunosuppressive drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Engraftment of insulin-producing cells from porcine islets in non-immune-suppressed rats or nonhuman primates transplanted previously with embryonic pig pancreas. Hammerman, MR.[2021]

The FDA has reviewed over 40 applications for using allogeneic pancreatic islets to treat type 1 diabetes, showing significant interest and progress in this area over the past 12 years.

Despite promising results from multiple centers in islet cell transplantation, there are still manufacturing and clinical trial design challenges that need to be addressed before allogeneic islets can be approved as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on regulatory issues in pancreatic islet transplantation. Wonnacott, K.[2019]

Islet allotransplantation has been performed for about 30 years to treat brittle type 1 diabetes, but its use is still limited to select patients due to challenges like the need for lifelong immunosuppression.

Research is ongoing to improve islet production, engraftment, and long-term function, including strategies like co-transplanting beta cell progenitors to enhance graft survival, with clinical trials anticipated in the near future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Islet transplantation 30 years after the first transplants. Antonioli, B., Galuzzi, M.[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. 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. 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. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1391504/full

Pancreatic islet transplantation: current advances and ... In conclusion, the latest research and clinical data unequivocally support the safety and efficacy of pancreatic islet cell transplantation in T1DM treatment.

6. ir.sana.com ir.sana.com/news-releases/news-release-details/sana-biotechnology-announces-positive-six-month-clinical-results

Release Details - Investor Relations | Sana Biotechnology, Inc The primary objective of the study is to investigate safety of UP421 transplantation in patients with type 1 diabetes, with secondary endpoints ...

7. diabetesjournals.org diabetesjournals.org/diabetes/article/74/9/1452/162981/Future-Directions-and-Clinical-Trial

Future Directions and Clinical Trial Considerations for Novel ... Type 1 diabetes results from the immune-mediated loss of insulin-producing pancreatic islet β-cells, rendering those affected dependent on ...