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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new cell therapy called cePolyTregs to help people with type 1 diabetes manage their blood sugar more effectively. The researchers aim to determine if adding these cells enhances the outcomes of an islet transplant, a procedure that places insulin-producing cells into the liver. The trial includes two groups: one receiving the new cell therapy and one undergoing only the transplant. Individuals with type 1 diabetes for over five years who experience severe low blood sugar or erratic glucose levels despite insulin use might be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new therapy.

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.

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

Research has shown that cePolyTregs, the special immune cells under study, have been safe in other conditions like type 1 diabetes and lupus. In these studies, patients generally handled the treatment well, with few serious side effects. This suggests that cePolyTregs might also be safe for people receiving islet transplants for diabetes. Although this trial remains in its early stages, the positive safety record from other studies is encouraging. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for Type 1 Diabetes, which typically involves insulin therapy, cePolyTregs introduces a new approach by using regulatory T cells, or Tregs. These cells are designed to help the immune system tolerate transplanted islet cells, potentially reducing the need for long-term insulin use. Researchers are excited about cePolyTregs because they target the root cause of Type 1 Diabetes by modulating the immune response, rather than just managing blood sugar levels. This represents a shift towards potentially achieving longer-term remission of the disease.

What evidence suggests that cePolyTregs might be an effective treatment for type 1 diabetes?

Research has shown that Treg cell therapy, such as cePolyTregs, holds promise for treating type 1 diabetes. In this trial, participants in the experimental arm will receive cePolyTregs two weeks after an islet transplant to evaluate its safety and preliminary efficacy. Studies have found that similar treatments, like PTG-007, have enabled some patients to go up to 12 years without needing insulin. Patients who received higher doses experienced better outcomes. This therapy uses Tregs to help the immune system stop attacking the body's own cells, potentially improving the success of islet transplants. These findings suggest that cePolyTregs could enhance blood sugar control in type 1 diabetes. ^{1 6 7 8 9}

Who Is on the Research Team?

James Shapiro, MD, PhD

Principal Investigator

University of Alberta

Indri Purwana, PhD

Principal Investigator

University of Alberta

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. poltreg.com poltreg.com/poltreg-treg-cell-therapy-for-patients-with-type-1-diabetes-shows-long-term-clinical-remission-and-insulin-independence/

PolTREG Treg cell therapy for patients with type-1 diabetes ... Treatment with its Treg cell therapy, PTG-007, resulted in clinical remission for up to 12 years in patients with type-1 diabetes (T1D).

2. withpower.com withpower.com/trial/phase-1-diabetes-mellitus-type-1-4-2022-17ced

Cell Transplant for Type 1 Diabetes (cePolyTregs Trial) 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 ...

3. clinicaltrialsarena.com clinicaltrialsarena.com/news/easd-2024-poltreg-t-cell-therapy-long-term-remission-type-1-diabetes/

EASD 2024: PolTREG's T cell therapy shows long-term ... PolTREG has presented positive long-term data for its cell therapy, PTG-007, showing that the therapy induced clinical remission for type 1 diabetes (T1D) for ...

4. poltreg.com poltreg.com/positive-results-of-a-long-term-safety-and-efficacy-study-of-ptg-007-in-early-onset-type-1-diabetes/

Positive results of a long-term safety and efficacy study ... We believe that PTG-007 has the potential to prevent type-1 diabetes, freeing patients of the life-long burden of having to take frequent insulin injections.

5. ainvest.com ainvest.com/news/poltreg-t1d-therapy-breakthrough-convergence-clinical-regulatory-catalysts-driving-cell-therapy-innovation-2508/

PolTREG's T1D Therapy Breakthrough: A Convergence of ... - Adaptive Phase 2/3 trial design and inclusion of Polish patients accelerate data readouts, showing up to 10-year insulin independence in some ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11951698/

Immunotherapies for prevention and treatment of type 1 diabetes This review discusses different types of immunotherapies with the goal of preventing or treating T1D.

7. sciencedirect.com sciencedirect.com/science/article/pii/S0009898124020710

Cluster of differentiation molecules in the metabolic ... Clinical trials evaluating the safety and efficacy of cePolyTregs in conjunction with islet transplantation provide valuable insights into the ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9714335/

Foxp3+ regulatory T cell therapy for tolerance in autoimmunity ... Additionally, its safety and efficacy as a therapy has been shown in both SLE and type 1 diabetes (144–148). Further modifications of IL-2 have been pursued ...

9. go.drugbank.com go.drugbank.com/conditions/DBCOND0029465

Type 1 Diabetes Mellitus (DBCOND0029465) Observational Study to Evaluate Safety of Levemir® in Type 1 and Type 2 Diabetes ... Home Telemedicine to Optimize Health Outcomes in High-Risk Youth With Type 1 ...