Cell Transplant for Type 1 Diabetes

(cePolyTregs Trial)

Overseen By Saira Qureshi

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Alberta

Must not be taking: Steroids, Anticoagulants

Disqualifiers: Cardiac disease, Substance abuse, others

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

Compensation: Varies

Number of Visits: 2

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes those on chronic steroid treatment or anticoagulant therapy (except aspirin). It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment cePolyTregs for type 1 diabetes?

Research shows that stem cell therapies, which include components similar to cePolyTregs, can help improve insulin production and reduce the need for insulin in people with type 1 diabetes. These therapies work by helping the body regenerate insulin-producing cells and balance the immune system. ^{1 2 3 4 5}

Is cell transplantation for type 1 diabetes safe?

Islet transplantation, a type of cell transplant for type 1 diabetes, has been shown to be safe for patients with severe hypoglycemia and those already on immunosuppressive drugs, although it requires donor cells and immunosuppression. ^{1 6 7 8 9}

How is the treatment cePolyTregs different from other treatments for type 1 diabetes?

The treatment cePolyTregs is unique because it involves the use of regulatory T cells (a type of immune cell) to potentially modulate the immune system and protect insulin-producing cells in the pancreas, which is different from traditional treatments that focus on insulin replacement or beta cell transplantation. ^{1 5 10 11 12}

What is the purpose of this trial?

This trial is testing a new treatment using special immune cells called cePolyTregs to help people with type 1 diabetes who are getting islet transplants. These cells help protect the transplanted insulin-producing cells from being attacked by the immune system, improving their function and survival.

Research Team

James Shapiro, MD, PhD

Principal Investigator

University of Alberta

Indri Purwana, PhD

Principal Investigator

University of Alberta

Eligibility Criteria

This trial is for adults aged 18-68 with Type 1 Diabetes (T1DM) who've had it for over 5 years and struggle with blood sugar control despite trying hard. They should have issues sensing low blood sugar or have been hospitalized for related complications within the last year. Participants need to understand the study, agree to its terms, and not be on certain medications like anticoagulants or planning pregnancy.

Inclusion Criteria

I understand the study's risks and have signed the consent form.

You are not able to sense when your blood sugar gets too low, or your blood sugar levels are hard to control even with a lot of insulin.

You have trouble noticing when your blood sugar gets too low, and it has caused serious problems in the past year.

Exclusion Criteria

I have Graves' disease but have been treated with radioiodine.

I am on long-term steroids for another health issue.

I do not have active infections like Hepatitis C, B, HIV, or TB.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Islet Transplantation

Participants receive islet transplantation as part of the study protocol

1 day

1 visit (in-person)

cePolyTregs Infusion

Participants receive cePolyTregs infusion two weeks post islet transplant

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and preliminary efficacy of cePolyTregs therapy

52 weeks

Regular visits as per protocol

Treatment Details

Interventions

• cePolyTregs

Trial Overview The trial tests cePolytreg cells in people receiving Islet transplants to manage T1DM. These special cells might help patients accept their new insulin-producing cells without needing lifelong anti-rejection drugs by preventing unwanted immune responses that could damage the transplant.

Participant Groups

Group I: Treatment Experimental Treatment 1 Intervention

Participants will receive cePolyTregs (target 400-1600 million, with a minimal acceptable dose of 100 million) two weeks post islet transplant and will be followed for 1 year after cePolyTregs infusion to assess the safety and preliminary efficacy of cePolyTregs therapy.

Group II: Control Active Control 1 Intervention

The Participants in this arm receive islet transplant only and no cePolyTregs.

Who Is Running the Clinical Trial?

University of Alberta

Lead Sponsor

Trials

957

Recruited

437,000+

Juvenile Diabetes Research Foundation Canadian Clinical Trial Network

Collaborator

Trials

1

Recruited

10+

Juvenile Diabetes Research Foundation

Collaborator

Trials

237

Recruited

142,000+

Findings from Research

Stem cell therapy significantly increased C-peptide levels and reduced glycated hemoglobin levels in patients with type 1 diabetes mellitus (T1DM), indicating improved insulin production and blood sugar control based on a meta-analysis of 22 studies.

The most effective outcomes were observed in patients aged 18 and older or those with a medical history of less than 3 months, particularly when higher doses of stem cells (≥107 IU/kg/day) were used, suggesting that patient characteristics and treatment protocols can influence the efficacy of stem cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stem cell transplantation for the treatment of patients with type 1 diabetes mellitus: A meta-analysis. Gan, J., Wang, Y., Zhou, X.[2020]

The Stem Cell Educator therapy, which uses cord blood-derived multipotent stem cells to modulate the immune system, has shown promising results in reversing autoimmunity in patients with long-standing Type 1 diabetes (T1D).

In a clinical trial, a single treatment led to the regeneration of pancreatic islet β cells and improved metabolic control, highlighting a potential new approach to treating T1D that differs from conventional methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stem cell educator therapy and induction of immune balance. Zhao, Y.[2021]

In a study involving 29 patients with established type 1 diabetes, those who received umbilical cord mesenchymal stromal cell (MSC) and autologous bone marrow mononuclear cell (aBM-MNC) transplantation showed significantly lower rates of chronic complications like peripheral neuropathy (7.1% vs. 46.7%) and diabetic nephropathy (7.1% vs. 40.0%) compared to the control group after 8 years.

The co-transplantation treatment was associated with a lower overall incidence of complications, with only 14.3% of patients in the SCT group developing any complications compared to 73.3% in the control group, indicating a potential long-term safety and efficacy of this stem cell therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention of chronic diabetic complications in type 1 diabetes by co-transplantation of umbilical cord mesenchymal stromal cells and autologous bone marrow: a pilot randomized controlled open-label clinical study with 8-year follow-up. Wu, Z., Xu, X., Cai, J., et al.[2022]

Type 1 diabetes is increasingly common, affecting about 1 in 300 people, and early intervention during the prediabetic phase, identified by islet autoantibodies, is crucial for potential prevention.

Current therapies, including monoclonal antibodies and immunosuppressants, have not yet achieved long-term remission or prevention of type 1 diabetes, highlighting the need for a balance between safety and efficacy in developing new treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention strategies for type 1 diabetes mellitus: current status and future directions. Winter, WE., Schatz, D.[2018]

Islet transplantation can potentially cure Type 1 diabetes by replacing the destroyed insulin-secreting beta-cells, but the limited availability of donor islets has hindered its widespread use.

Recent studies indicate that xenografts, tissue stem cells, and embryonic stem cells could serve as alternative sources for insulin-producing cells, with embryonic stem cells being particularly promising due to their ability to generate large quantities of cells for transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cell-based treatments for diabetes. Jones, PM., Courtney, ML., Burns, CJ., et al.[2008]

References

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

Microvessels enhance vascularization and function of transplanted insulin-producing cells. [2022]

2. Greece pubmed.ncbi.nlm.nih.gov

Stem cell transplantation for the treatment of patients with type 1 diabetes mellitus: A meta-analysis. [2020]

3. Ireland pubmed.ncbi.nlm.nih.gov

Stem cells: An emerging novel therapeutic for type-1 diabetes mellitus. [2018]

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

Stem cell educator therapy and induction of immune balance. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Prevention of chronic diabetic complications in type 1 diabetes by co-transplantation of umbilical cord mesenchymal stromal cells and autologous bone marrow: a pilot randomized controlled open-label clinical study with 8-year follow-up. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Advances in β-cell replacement therapy for the treatment of type 1 diabetes. [2021]

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

Combination Immunotherapy for Type 1 Diabetes. [2019]

8. Japan pubmed.ncbi.nlm.nih.gov

Current state and future evolution of pancreatic islet transplantation. [2023]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Prevention strategies for type 1 diabetes mellitus: current status and future directions. [2018]

10. Belgium pubmed.ncbi.nlm.nih.gov

Therapies aimed at preservation or restoration of beta cell function in type 1 diabetes. [2018]

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

From the dish to humans: A stem cell recipe for success. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Cell-based treatments for diabetes. [2008]