Islet Transplantation + Immune Cell Therapy for Type 1 Diabetes

Overseen By Stephan Busque, MD, MS

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Stanford University

Must be taking: Insulin

Must not be taking: Anti-diabetics, Investigational agents

Disqualifiers: Obesity, Hypertension, Infections, others

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

Compensation: Varies

Number of Visits: 6

Duration: Within 2 years

24 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

The trial requires that you stop taking any anti-diabetic medication other than insulin within 4 weeks of enrollment. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

What data supports the effectiveness of the treatment Islet Transplantation + Immune Cell Therapy for Type 1 Diabetes?

Research shows that bone marrow transplantation can help prevent diabetes in animal models by improving immune function and reducing harmful immune responses. Additionally, mesenchymal stem cell infusions have been shown to preserve insulin-producing cell function and reduce inflammation in both patients and animal models with severe diabetes. ^{1 2 3 4 5}

Is islet transplantation with immune cell therapy safe for humans?

Islet transplantation has been studied for safety in humans, with data showing that larger islet numbers and older recipient age are linked to better outcomes. However, there are concerns about the toxicity of the immunosuppressive drugs used to prevent rejection of the transplanted cells. ^{2 5 6 7 8}

How does the treatment for Type 1 Diabetes involving Islet Transplantation and Immune Cell Therapy differ from other treatments?

This treatment is unique because it combines islet transplantation with immune cell therapy to potentially restore the body's ability to tolerate its own insulin-producing cells, reducing the need for lifelong immunosuppression. It aims to both replace damaged cells and modulate the immune system to prevent further autoimmune attacks, which is different from standard treatments that primarily focus on managing blood sugar levels. ^{3 4 5 9 10}

What is the purpose of this trial?

The goal of this clinical trial is to learn if patients who have brittle type 1 diabetes receiving an islet transplantation will have better control of their sugars if they also receive one of 2 types of immune cells along with the islet transplant. The participants will receive either their own immune cells, called regulatory T cells, or immune cells from the bone marrow of the islet donor.

Research Team

Stephan Busque, MD, MS

Principal Investigator

Stanford University

Eligibility Criteria

Adults aged 18-70 with brittle type 1 diabetes, not suitable for pancreas transplant, under intensive diabetes management, and experiencing severe hypoglycemia unawareness. Must be mentally stable to follow the study protocol and use dual contraception if of childbearing potential.

Inclusion Criteria

At least two episodes of severe hypoglycemia in the 12 months prior to study enrollment

I am not pregnant and agree to use 2 forms of birth control during the study.

Absence of stimulated C peptide (< 0.3 ng/mL) in response to a mixed meal tolerance test measured at 60 and 90 minutes after the start of consumption

Exclusion Criteria

I haven't had a serious fungal infection in the last year.

Baseline Hb below the lower limits of normal; neutropenia (<1,500/7L), or thrombocytopenia (platelets <100,000/7L)

Presence or history of macroalbuminuria (>500mg/g creatinine)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive islet transplantation along with either regulatory T cells or donor-derived vertebral bone marrow cells

Within 2 years

Follow-up

Participants are monitored for safety, glucose control, and adverse events post-islet transplantation

24 months

assessed at 6, 12, and 24 months

Long-term monitoring

Continued monitoring of glucose variability, hypoglycemia, and quality of life

Long-term

Treatment Details

Interventions

• Donor Derived Vertebral Bone Marrow infusion
• Recipient T regulatory cell infusion

Trial Overview The trial is testing whether adding immune cells (either the patient's own regulatory T cells or donor bone marrow cells) to an islet cell transplant helps better control blood sugar in people with brittle type 1 diabetes.

Participant Groups

Group I: Recipient T Regulatory Cell Experimental Treatment 1 Intervention

T regulatory cells prior to islet transplantation, induction therapy with ATG and Belatacept and maintenance immunosuppression with Tacrolimus Extended-release tablets (Envarsus XR) and Mycophenolate Mofetil (MMF).

Group II: Donor Derived Vertebral Bone Marrow Experimental Treatment 1 Intervention

Deceased donor vertebral bone marrow (VBM) cells, induction therapy with ATG and Belatacept and maintenance immunosuppression with Tacrolimus Extended-release tablets (Envarsus XR) and Mycophenolate Mofetil (MMF).

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

University of California, San Francisco

Collaborator

Trials

2,636

Recruited

19,080,000+

Findings from Research

The transplantation of umbilical cord mesenchymal stromal cells (UC-MSC) combined with autologous bone marrow mononuclear cells (aBM-MNC) in 42 patients with established type 1 diabetes (T1D) was found to be safe and well-tolerated, showing no significant adverse effects over the one-year follow-up period.

Patients receiving the stem cell treatment experienced significant improvements in insulin secretion and metabolic control, including a 105.7% increase in C-peptide levels and a 12.6% reduction in HbA1c, while control subjects showed declines in these measures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Umbilical Cord Mesenchymal Stromal Cell With Autologous Bone Marrow Cell Transplantation in Established Type 1 Diabetes: A Pilot Randomized Controlled Open-Label Clinical Study to Assess Safety and Impact on Insulin Secretion. Cai, J., Wu, Z., Xu, X., et al.[2022]

Islet transplantation outcomes for type 1 diabetes have improved over time, with insulin independence rates increasing from 27% in 1999-2002 to 44% in 2007-2010, indicating enhanced efficacy of the procedure.

Safety outcomes also improved, as evidenced by a lower rate of islet reinfusion (48% in 2007-2010 compared to 60-65% in earlier years) and a reduction in adverse events, suggesting a more favorable risk profile for recent transplant recipients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improvement in outcomes of clinical islet transplantation: 1999-2010. Barton, FB., Rickels, MR., Alejandro, R., et al.[2022]

References

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

Immunological Basis for Rapid Progression of Diabetes in Older NOD Mouse Recipients Post BM-HSC Transplantation. [2020]

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

Umbilical Cord Mesenchymal Stromal Cell With Autologous Bone Marrow Cell Transplantation in Established Type 1 Diabetes: A Pilot Randomized Controlled Open-Label Clinical Study to Assess Safety and Impact on Insulin Secretion. [2022]

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

Inducing tolerance to MHC-matched allogeneic islet grafts in diabetic NOD mice by simultaneous islet and bone marrow transplantation under nonirradiative and nonmyeloablative conditioning therapy. [2019]

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

Prevention of type I diabetes in nonobese diabetic mice by allogenic bone marrow transplantation. [2022]

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

Infusion with Human Bone Marrow-derived Mesenchymal Stem Cells Improves β-cell Function in Patients and Non-obese Mice with Severe Diabetes. [2018]

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

Improvement in outcomes of clinical islet transplantation: 1999-2010. [2022]

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

Considerations and challenges of islet transplantation and future therapies on the horizon. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Durable Control of Autoimmune Diabetes in Mice Achieved by Intraperitoneal Transplantation of "Neo-Islets," Three-Dimensional Aggregates of Allogeneic Islet and "Mesenchymal Stem Cells". [2019]

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

Induction of donor-specific tolerance to islet allografts in nonhuman primates. [2019]

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

Elimination of insulitis and augmentation of islet beta cell regeneration via induction of chimerism in overtly diabetic NOD mice. [2018]