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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to assist people with type 1 diabetes by transplanting insulin-producing cells under the skin instead of in the liver. The goal is to improve blood sugar control without the complications of liver transplants and to simplify cell monitoring. The trial involves implanting a nylon catheter, known as the device-less sentinel unit, to facilitate this process. It seeks participants who have difficulty sensing low blood sugar or experience unstable blood sugar levels that disrupt daily life. This new approach could provide a better option for those struggling to manage their diabetes. 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 approach.

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 prior data suggests that this device-less technique is safe for islet transplantation?

Research has shown that islet transplantation can help manage type 1 diabetes by restoring blood sugar control. However, limited safety information exists for this new method, which involves placing insulin-producing cells under the skin using a nylon tube. Since this study is in its early phase, the main focus is to test the treatment's safety.

Past studies have generally found islet transplantation to be safe. However, this specific method without a device remains new. As this study is just beginning, it primarily aims to assess the treatment's safety and identify any possible side effects.

Prospective participants should note that early trials like this one are designed to gather safety information. The goal is to find a new way to help people with type 1 diabetes, but this technique is still under careful study. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about device-less islet transplantation for Type 1 Diabetes because it offers a novel approach compared to existing treatments like insulin therapy and traditional islet transplantation. Unlike standard methods, this treatment uses a nylon catheter as a "device-less sentinel" to implant islet cells, which could potentially reduce the need for lifelong insulin injections. Additionally, the use of ultrasound monitoring and a less invasive implantation technique may improve patient comfort and outcomes. This innovative method aims to enhance the body's ability to regulate blood sugar naturally, offering a promising alternative to current diabetes management strategies.

What evidence suggests that this device-less technique is effective for islet transplantation in type 1 diabetes?

Research has shown that islet transplantation can effectively help control blood sugar levels in people with type 1 diabetes. In this trial, participants will undergo a new technique that involves implanting insulin-producing cells under the skin without using any devices. This method allows the body to grow new blood vessels to support these cells. In studies with mice, this technique reversed type 1 diabetes without requiring drugs to prevent cell rejection. This innovative approach aims to simplify monitoring and ensure cell survival without the typical immune reaction that causes cell loss. While more research is needed, these early findings are promising for improving diabetes management. ^{1 6 7 8 9}

Who Is on the Research Team?

James Shapiro, MD, PhD

Principal Investigator

University of Alberta

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. withpower.com withpower.com/trial/phase-1-diabetes-mellitus-type-1-9-2021-cfa3a

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 ...

2. medicalxpress.com medicalxpress.com/news/2023-12-under-the-skin-implant-diabetes.html

Under-the-skin implant could treat type I diabetes A new technique to treat type 1 diabetes: implanting a device inside a pocket under the skin that can secrete insulin while avoiding the immunosuppression.

3. newatlas.com newatlas.com/medical/subcutaneous-pancreatic-cell-implant-type-1-diabetes-without-immunosuppression/

Under-skin implant reverses type 1 diabetes without anti- ... The device reversed type 1 diabetes in mice and didn't require the administration of anti-rejection drugs. The device could one day provide an ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8563008/

A nanofibrous encapsulation device for safe delivery of ... A nanofibrous encapsulation device for safe delivery of insulin-producing cells to treat type 1 diabetes

5. breakthrought1d.org breakthrought1d.org/news-and-updates/new-breakthrough-t1d-publication-paving-the-way-for-beta-cell-replacement-therapies/

New Breakthrough T1D publication paves the way for cell ... Breakthrough T1D's newest publication outlines a roadmap for beta cell replacement therapies for type 1 diabetes.

6. clinicaltrials.breakthrought1d.ca clinicaltrials.breakthrought1d.ca/clinical-trial/NCT05073302

Device-Less Technique in Islet Transplantation Islet transplantation is an effective modality for treating type 1 diabetes. ... Procedure : Implantation of Nylon catheter (Device-less sentinel unit).

7. ctv.veeva.com ctv.veeva.com/study/device-less-technique-in-islet-transplantation

Device-Less Technique in Islet Transplantation - ClinicalTrials.Veeva Islet transplantation is an effective modality for treating type 1 diabetes ... Procedure: Implantation of Nylon catheter (Device-less sentinel unit) ... Data ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10614671/

Preferred Islet Delivery Device Characteristics and ... The main outcome of our cross-sectional study in a large group of Dutch patients with type 1 diabetes is that patients with T1D are willing to ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT00679042

NCT00679042 | Islet Transplantation in Type 1 Diabetic ... This study is a Phase 3 single center, uncontrolled trial in which 1-3 allogeneic pancreatic islet transplants are performed for each study subject.