Islet Transplantation + Immune Cell Therapy for Type 1 Diabetes

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Stephan Busque, MD, MS profile photo
Overseen ByStephan Busque, MD, MS
Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: Stanford University
Must be taking: Insulin
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if people with brittle type 1 diabetes, who struggle to control their blood sugar, benefit more from islet transplantation when they also receive special immune cells. Participants will receive either their own regulatory T cells (a type of immune cell that helps control the immune response) or cells from the bone marrow of the islet donor (Donor Derived Vertebral Bone Marrow infusion). Those who have had type 1 diabetes for at least 5 years and experience frequent episodes of severe low blood sugar might be a good fit for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that stem cells from bone marrow, like those used in certain bone marrow infusions, are generally safe. They are often used in studies because most patients tolerate them well. Although no major safety issues have emerged, further research is needed to fully understand their effects.

Similarly, studies on regulatory T cell infusions have shown they are mostly safe. In one study, most patients experienced no serious problems, though one person developed a fever after treatment. This indicates that while these treatments are generally safe, mild side effects can occur.

Both treatments are in early trial stages, so researchers focus primarily on ensuring their safety for people.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for Type 1 Diabetes because they offer a novel approach to managing the condition. Unlike standard treatments that typically focus on insulin replacement, these therapies aim to address the underlying immune dysfunction. The donor-derived vertebral bone marrow infusion introduces new stem cells that could help regenerate healthy islets and immune tolerance, while the recipient T regulatory cell infusion works to modulate the immune system, potentially reducing the autoimmune attack on insulin-producing cells. These innovative strategies could lead to more durable and effective management of Type 1 Diabetes, shifting the focus from symptom management to addressing root causes.

What evidence suggests that this trial's treatments could be effective for type 1 diabetes?

This trial will compare two experimental treatments for type 1 diabetes. One treatment arm uses donor-derived vertebral bone marrow cells. Research has shown that stem cells from bone marrow might help treat type 1 diabetes, with studies in rats finding that these cells can help control blood sugar levels. In humans, some early tests suggested possible benefits, but more proof is needed.

The other treatment arm involves the infusion of recipient T regulatory cells. These special immune cells help manage the body's immune response. Previous research has found challenges with their long-term effectiveness, but they have shown some promise in managing type 1 diabetes. The idea is that these cells might help protect transplanted islets and improve blood sugar control. More research is needed to confirm these findings in humans.14678

Who Is on the Research Team?

Stephan Busque | Stanford Medicine

Stephan Busque, MD, MS

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

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
See 7 more

Exclusion Criteria

Baseline Hb below the lower limits of normal; neutropenia (<1,500/7L), or thrombocytopenia (platelets <100,000/7L)
I haven't had a serious fungal infection in the last year.
Presence or history of macroalbuminuria (>500mg/g creatinine)
See 24 more

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.
How Is the Trial Designed?
2Treatment groups
Experimental Treatment
Group I: Recipient T Regulatory CellExperimental Treatment1 Intervention
Group II: Donor Derived Vertebral Bone MarrowExperimental Treatment1 Intervention

Find a Clinic Near You

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+

Published Research Related to This Trial

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

Citations

Bone Marrow-Derived Stem Cell Transplantation for the ...This article reviews the progress in the field of BMC for the treatment of subjects with insulin-dependent diabetes, and summarizes clinical data of pilot ...
Efficiency of Bone Marrow-Derived Mesenchymal Stem ...This study aims to evaluate the effectiveness of the bone marrow-derived mesenchymal stem cells (BM-MSCs) and hesperetin in the treatment of a T1DM rat model.
NCT05973734 | Islet Transplantation With Recipient T-Reg ...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 ...
The Potential Utility of Bone Marrow or Umbilical Cord ...The Potential Utility of Bone Marrow or Umbilical Cord Blood Transplantation For the Treatment of Type I Diabetes Mellitus. Mohamed Mabed.
Efficacy of Autologous Bone Marrow–Derived Stem Cell ...A total of 10 patients (8 men) with T2DM for >5 years, failure of triple oral antidiabetic drugs, currently on insulin (≥0.7 U/kg/day) at least for 1 year, and ...
a systematic review and meta-analysis - PMC - PubMed CentralAlthough meta-analysis illustrated the SCT is associated with T1DM improvement, well-designed randomized clinical trials are needed to clarify its efficacy.
Stem Cells Therapy for Diabetes Mellitus Type 1. An ...Because of their proven safety, bone marrow-derived MSCs are the most frequently applied stem cell source today. However, there are several ...
Efficacy and Safety of Autologous Bone Marrow-Derived ...This prospective, randomized, single-blinded placebo-controlled study evaluates the efficacy and safety of autologous bone marrow-derived stem cell ...
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