Device-Less Islet Transplantation for Type 1 Diabetes

Overseen By Peter Senior, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Alberta

Disqualifiers: Cardiac disease, Substance abuse, Psychiatric disorder, Infections, others

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

Compensation: Varies

Number of Visits: 6

5 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new method of transplanting insulin-producing cells under the skin for people with type 1 diabetes who struggle with standard treatments. The technique uses a small tube to create a supportive environment for the cells. This approach aims to improve blood sugar control by helping the transplanted cells survive and function effectively. This method is being explored as an alternative to insulin therapy, especially for those with severe blood sugar issues.

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

The trial protocol does not specify if you need to stop taking your current medications. However, if you have a psychiatric disorder that is unstable or uncontrolled on current medication, you may not be eligible to participate.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have a psychiatric disorder that is unstable or uncontrolled on current medication, you may not be eligible to participate.

What data supports the idea that Device-Less Islet Transplantation for Type 1 Diabetes is an effective treatment?

The available research shows that Device-Less Islet Transplantation can effectively manage Type 1 Diabetes. In a study with mice, this method reversed diabetes in 91% of the subjects and maintained normal blood sugar levels for over 100 days. This approach was successful even in mice with pre-existing diabetes and those with a strong immune response. Compared to other methods, this treatment does not require a permanent device, making it a promising option for diabetes management. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment 'Device-Less Islet Transplantation for Type 1 Diabetes'?

Research shows that islet transplantation can help control blood sugar levels in people with type 1 diabetes, and using a prevascularized subcutaneous site for transplantation has been effective in reversing diabetes in mouse models. This approach avoids the need for a permanent device and has shown promising results in maintaining normal blood sugar levels. ^{1 2 3 4 5}

What safety data exists for device-less islet transplantation for Type 1 Diabetes?

The provided research does not contain safety data for device-less islet transplantation or related procedures like nylon catheter implantation or angiocatheter implantation. The studies focus on the use of drug-eluting stents in diabetic patients, which is unrelated to the treatment in question. ^{6 7 8 9 10}

Is the treatment 'Implantation of Nylon catheter (Device-less sentinel unit)' a promising treatment for type 1 diabetes?

Yes, the treatment is promising. It involves a new way to transplant cells that make insulin, which can help people with type 1 diabetes. This method doesn't need a permanent device and has shown success in reversing diabetes in animal studies. It offers a simpler and safer option for managing diabetes. ^{2 3 4 5 11}

How is the treatment 'Implantation of Nylon catheter (Device-less sentinel unit)' for type 1 diabetes different from other treatments?

This treatment is unique because it involves transplanting islets into a pre-prepared subcutaneous space without the need for a permanent device or immunosuppressive drugs, unlike traditional methods that often require placing islets in the liver and using lifelong medication to prevent rejection. ^{1 2 4 5 11}

Research Team

James Shapiro, MD, PhD

Principal Investigator

University of Alberta

Eligibility Criteria

This trial is for adults with Type 1 Diabetes who have unstable blood sugar levels, frequent hospital visits due to diabetic ketoacidosis, or reduced awareness of hypoglycemia. They must understand the study and consent to participate. Excluded are those under 18 or over 68, with certain medical conditions like severe heart disease, kidney issues, psychiatric disorders, high insulin requirements, pregnancy intentions without contraception use, substance abuse history including smoking within the last six months.

Inclusion Criteria

Your blood sugar levels are not well controlled and have caused problems with your daily activities, or you have been to the hospital for diabetic ketoacidosis in the past year.

Participants must be capable of understanding the purpose and risks of the study and must sign a statement of informed consent.

You have trouble recognizing when your blood sugar levels are low and have experienced severe low blood sugar episodes that needed help from someone else within the last year.

Exclusion Criteria

Psychiatric disorder making the subject not a suitable candidate for transplantation (e.g., schizophrenia, bipolar disorder, or major depression that is unstable or uncontrolled on current medication).

You need more than 1 unit of insulin per kilogram of body weight each day.

Positive pregnancy test, intent for future pregnancy or male subjects' intent to procreate, failure to follow effective contraceptive measures, or presently breast-feeding.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

DL Sentinel Unit Implantation

Implantation of the DL sentinel unit in the forearm, with local or general anesthesia

2-24 weeks prior to islet transplant

1 visit (in-person)

Islet Transplantation

Simultaneous portal and subcutaneous islet transplantation in the DL sentinel spaces

Day 0

1 visit (in-person)

Explantation of DL Sentinels

Explantation of DL sentinel units at 2, 4, 12, and 24 weeks post islet transplant

24 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including post-transplant testing and visits

9 months

Multiple visits (in-person and virtual)

Treatment Details

Interventions

• Implantation of Nylon catheter (Device-less sentinel unit)

Trial Overview The trial tests a 'device-less' technique for transplanting insulin-producing cells under the skin in patients with Type 1 Diabetes. This method uses a temporary nylon catheter to create a favorable environment for cell survival by promoting new blood vessel growth without triggering adverse body reactions.

Participant Groups

Group I: Treatment Group Experimental Treatment 1 Intervention

Implantation of the Device-Less sentinel units. Ultrasound Monitoring. Islet Transplantation. Explantation of Device-Less Sentinels. Standard of Care. Concomitant Care. Post Transplant Testing and Visits. Participant Retention (nine month follow up assessment).

Who Is Running the Clinical Trial?

University of Alberta

Lead Sponsor

Trials

957

Recruited

437,000+

Juvenile Diabetes Research Foundation

Collaborator

Trials

237

Recruited

142,000+

Findings from Research

Islet transplantation has emerged as a promising treatment for type 1 diabetes, offering better metabolic control than exogenous insulin, although it requires lifelong immunosuppression and is limited by the availability of donor organs.

The focus of islet transplantation has shifted from achieving complete insulin independence to maintaining good blood glucose control and preventing severe hypoglycemic episodes, allowing more patients to benefit from the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Islet transplantation in type I diabetes mellitus]. Lehmann, R., Pavlicek, V., Spinas, GA., et al.[2015]

Transplanting islets into the kidney resulted in a 100% success rate for murine islets and a 75-80% success rate for human islets in curing diabetes, while the portal vein showed only a 60% success rate for murine islets.

Skeletal muscle transplantation demonstrated equivalent or superior glucose-lowering effects compared to the portal vein, suggesting it could be a more accessible and effective site for future human islet transplant trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transplantation sites for human and murine islets. Stokes, RA., Cheng, K., Lalwani, A., et al.[2019]

A new method called replenishable prevascularized implantation methodology (RPVIM) significantly improves the survival and function of insulin-producing beta cells in type 1 diabetes patients by enhancing blood supply to encapsulated cells, with over 75% of devices showing positive signals after 28 days.

Compared to standard methods, RPVIM devices not only had better engraftment but also maintained the functionality of the beta cell clusters, which is essential for effective blood glucose regulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Replenishable prevascularized cell encapsulation devices increase graft survival and function in the subcutaneous space. Chendke, GS., Kharbikar, BN., Ashe, S., et al.[2023]

In a study involving diabetic rats, the implantation of agarose rods containing the cyclic oligopeptide SEK-1005 successfully created vascularized pockets that allowed for the transplantation of islet cells without the need for immunosuppressive drugs.

Out of 10 recipients, 8 showed long-term survival of the transplanted islet grafts, with the mechanism of acceptance linked to the formation of granulomatous tissue and regulatory T cells that helped suppress immune responses against the grafts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term Functioning of Allogeneic Islets in Subcutaneous Tissue Pretreated With a Novel Cyclic Peptide Without Immunosuppressive Medication. Kuwabara, R., Hamaguchi, M., Fukuda, T., et al.[2022]

Transplanting donor-derived islets into a prevascularized subcutaneous site, created temporarily with a vascular access catheter, successfully reversed diabetes in 91% of mice, maintaining normal blood sugar levels for over 100 days.

This method proved effective even in mice with existing diabetes and those with a stronger inflammatory response, suggesting it could be a promising alternative to traditional transplantation methods without needing permanent devices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prevascularized subcutaneous device-less site for islet and cellular transplantation. Pepper, AR., Gala-Lopez, B., Pawlick, R., et al.[2021]

In a study involving 74 patients with diabetes and small coronary vessel disease, sirolimus-eluting stents (SESs) significantly reduced the rate of angiographic restenosis by about 60% compared to bare metal stents (BMSs), with rates of 25% for SESs versus 63% for BMSs.

SES implantation also led to a 15% absolute decrease in adverse clinical events, although patients with insulin-dependent diabetes mellitus still experienced a high restenosis rate of 40%, indicating that while SESs are more effective, some high-risk patients may still face challenges.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of sirolimus-eluting stent in diabetic patients with small coronary arteries (a SES-SMART substudy). Ortolani, P., Ardissino, D., Cavallini, C., et al.[2016]

In a study of 160 diabetic patients, sirolimus-eluting stents (SES) showed a significantly lower rate of target lesion revascularization at 2 years compared to bare metal stents (BMS), with rates of 7.7% for SES versus 35.0% for BMS (P < 0.001).

While SES demonstrated effectiveness in reducing revascularization rates, there was an increase in stent thrombosis occurrences after the withdrawal of clopidogrel, with three cases in the SES group compared to none in the BMS group, indicating a potential safety concern in the long-term management of these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term clinical benefit of sirolimus-eluting stent implantation in diabetic patients with de novo coronary stenoses: long-term results of the DIABETES trial. Jiménez-Quevedo, P., Sabaté, M., Angiolillo, DJ., et al.[2018]

In a study of type 2 diabetic patients, second-generation drug-eluting stents (DES) significantly reduced the rate of major adverse cardiac events (MACEs) to 3.3% compared to 10.0% for first-generation DES after 2 years, indicating improved safety and efficacy.

The lower rates of MACEs with second-generation DES were primarily due to reduced need for target lesion and vessel revascularization, highlighting their enhanced performance in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of clinical outcomes between first-generation and second-generation drug-eluting stents in type 2 diabetic patients. Jeong, HS., Cho, JY., Kim, EJ., et al.[2013]

In a study of 5051 diabetic patients followed for 3 years, drug-eluting stents (DES) were associated with significantly lower mortality rates (14.4% for DES vs. 22.2% for bare-metal stents (BMS)) and reduced rates of myocardial infarction and revascularization compared to BMS.

After adjusting for various factors, the risk-adjusted rates showed that DES led to a 3.2% lower mortality rate, a 3.0% lower rate of myocardial infarction, and a 5.4% lower rate of target vessel revascularization, indicating that DES are a safer and more effective option for diabetic patients undergoing coronary stenting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug-eluting or bare-metal stenting in patients with diabetes mellitus: results from the Massachusetts Data Analysis Center Registry. Garg, P., Normand, SL., Silbaugh, TS., et al.[2020]

The amphilimus-eluting stent (AES) demonstrated comparable long-term clinical outcomes to everolimus-eluting stents (EES) in patients with diabetes mellitus, showing similar rates of target-vessel failure, target-vessel revascularization, and target-lesion revascularization at 5 years.

The study, part of the RESERVOIR trial, indicates that AES effectively suppresses neointimal hyperplasia, maintaining its efficacy over a 5-year follow-up period without significant differences in major clinical endpoints compared to EES.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amphilimus- Versus Everolimus-Eluting Stents in Patients With Diabetes Mellitus: 5-Year Follow-Up of the RESERVOIR Trial. Ascencio-Lemus, MG., Romaguera, R., Brugaletta, S., et al.[2022]

Subcutaneous transplantation of pancreatic islets mixed with a viability matrix has been shown to achieve long-term blood sugar control (euglycaemia) in various animal models, including mice, pigs, and non-human primates.

This method addresses the challenges of islet transplantation by improving graft survival and function without the need for complex devices, making it a promising new approach for treating type 1 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Islet transplantation in the subcutaneous space achieves long-term euglycaemia in preclinical models of type 1 diabetes. Yu, M., Agarwal, D., Korutla, L., et al.[2021]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

[Islet transplantation in type I diabetes mellitus]. [2015]

2. Germany pubmed.ncbi.nlm.nih.gov

Transplantation sites for human and murine islets. [2019]

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

Replenishable prevascularized cell encapsulation devices increase graft survival and function in the subcutaneous space. [2023]

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

Long-term Functioning of Allogeneic Islets in Subcutaneous Tissue Pretreated With a Novel Cyclic Peptide Without Immunosuppressive Medication. [2022]

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

A prevascularized subcutaneous device-less site for islet and cellular transplantation. [2021]

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

Effect of sirolimus-eluting stent in diabetic patients with small coronary arteries (a SES-SMART substudy). [2016]

7. England pubmed.ncbi.nlm.nih.gov

Long-term clinical benefit of sirolimus-eluting stent implantation in diabetic patients with de novo coronary stenoses: long-term results of the DIABETES trial. [2018]

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

Comparison of clinical outcomes between first-generation and second-generation drug-eluting stents in type 2 diabetic patients. [2013]

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

Drug-eluting or bare-metal stenting in patients with diabetes mellitus: results from the Massachusetts Data Analysis Center Registry. [2020]

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

Amphilimus- Versus Everolimus-Eluting Stents in Patients With Diabetes Mellitus: 5-Year Follow-Up of the RESERVOIR Trial. [2022]

11. Germany pubmed.ncbi.nlm.nih.gov

Islet transplantation in the subcutaneous space achieves long-term euglycaemia in preclinical models of type 1 diabetes. [2021]