Pancreatic Cell Implants for Type 1 Diabetes

(SUGR Trial)

Recruiting at 1 trial location

Overseen By Mohammad Razvi

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Seraxis

Must be taking: Immunosuppressants

Must not be taking: Anti-diabetics, Weight loss

Disqualifiers: Type 2 diabetes, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This study will evaluate the safety, efficacy and durability of SR-02 administered to the omentum of patients of Type 1 diabetes with severe recurrent hypoglycemia. The study will also help establish the optimal treatment dose. Although this study is open to patients with all HLA or blood types, immunosuppression to prevent rejection will be required in this first in human study.

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.

What data supports the effectiveness of the treatment Allogeneic Pancreatic Endocrine Cell Clusters for Type 1 Diabetes?

Research shows that similar treatments, like islet transplantation, have improved metabolic control and reduced severe low blood sugar episodes in patients with Type 1 Diabetes. Additionally, studies on 'Neo-Islets' in animals have shown promising results in maintaining normal blood sugar levels without the need for anti-rejection drugs. ^{1 2 3 4 5}

Is the pancreatic cell implant treatment safe for humans?

Pancreatic cell implants, also known as allogeneic pancreatic islet transplants, have been reviewed by the FDA and are considered a standard treatment for type 1 diabetes in several countries. While there are challenges in manufacturing and licensing, the treatment has shown promising results in clinical trials, and procedure-related risks are being refined. ^{1 6 7 8 9}

How does the treatment of Allogeneic Pancreatic Endocrine Cell Clusters for Type 1 Diabetes differ from other treatments?

This treatment is unique because it uses 'Neo-Islets', which are 3-D organoids made from mesenchymal stromal and islet cells, to restore insulin production without the need for anti-rejection drugs. Unlike traditional pancreas or islet transplants, this approach is designed to be immune-protected and can potentially provide a long-term solution for Type 1 Diabetes by normalizing blood sugar levels. ^{2 10 11 12 13}

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Allogeneic Pancreatic Endocrine Cell Clusters (Cell Therapy)

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. United States 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. [2022]

2. United States 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. [2023]

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

Transplantation: current developments and future directions; the future of clinical islet transplantation as a cure for diabetes. [2019]

4. Italy pubmed.ncbi.nlm.nih.gov

Islet transplantation 30 years after the first transplants. [2019]

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

Transplantation of dispersed pancreatic islet tissue in humans: autografts and allografts. [2019]

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

Islet transplantation: current status and future directions. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

US food and drug administration (FDA) panel endorses islet cell treatment for type 1 diabetes: A pyrrhic victory? [2021]

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

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

9. England pubmed.ncbi.nlm.nih.gov

Islet cell transplant not justified. [2016]

10. United States 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. [2021]

11. United States 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. [2021]

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

Transplantation of Human Pancreatic Endoderm Cells Reverses Diabetes Post Transplantation in a Prevascularized Subcutaneous Site. [2018]

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

Histologic differentiation of human fetal pancreatic explants transplanted into nude mice. [2019]