Device-Less Technique in Islet Transplantation

NCT05073302 | Completed Phase 1 DMC

• 1 other identifier: Pro00090942
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

Islet transplantation is an effective modality for treating type 1 diabetes. Despite marked progress in clinical islet transplantation with the achievement and maintenance of insulin independence in over half of recipients up to 5 years, transplant approaches are limited to those that struggle to control their diabetes. Furthermore, this approach remains restricted due to the scarcity of human pancreas donors. While transplanting insulin-producing cells into the liver has been demonstrated as an efficacious means of restoring glycemic control to patients with T1D, the procedure often results in cell loss, and carries risks. Moreover, transplant in to the liver does not permit imaging or retrieval of donor islets. The ability to retrieve the cells is also important for safety reasons. In theory, the space under the skin is an attractive alternate site for transplanting insulin producing cell, due to ready access, and potential for monitoring cellular transplant function through novel imaging techniques. However, transplantation of insulin producing cells into an unmodified site under the skin universally fails to reverse diabetes in research animal models, or in human studies. Other techniques using devices with different type of technologies and biomaterials have been explored with variable success. Unfortunately, the foreign body and inflammatory reaction persist in the implant. Shapiro Lab, has developed a novel technique called 'device-less' (DL) transplant modality. This approach was designed to harness an innate foreign body response in a favorable and controlled manner, to induce growth of new blood vessels to allow the survival of the insulin producing cells without the natural body response to foreign body. Briefly, this site transforms the inhospitable under the skin site into a viable location through the temporary implantation of a small tube called angiocatheter. For this study, 5 patients will received transplant in to the modified site under the skin using the DL transplant technique.

Conditions

Type 1 Diabetes

Keywords

Device-less, Islet Transplantation

Outcome Measures

Primary Outcomes (2)

• Rate of Adverse Events/Serious Adverse Events

  Adverse Events/ Serious Adverse Event experienced by the participants in the study

  9 months

• Rate of inflammation in the DL implant site

  Implant tolerability assessment

  9 months

Secondary Outcomes (5)

• Probability of rejection or injury analyzed using the Molecular Microscope Diagnostic System (MMDx) system by measuring the expressions of all genes within the graft

  9 months

• Percentage of live cells measured by immunohistochemistry

  9 months

• Presence of vascularization demonstrated by immunohistochemistry

  9 months

• Presence of immune response demonstrated by immunohistochemistry

  9 months

• Cellular composition demonstrated by immunohistochemistry

  9 months

Study Arms (1)

Treatment Group

EXPERIMENTAL

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).

Procedure: Implantation of Nylon catheter (Device-less sentinel unit)

Interventions

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

Implantation of the Device-Less sentinel units. Ultrasound monitoring will be performed after Device-Less implantation. Standard Islet cell Transplantation: Will occur simultaneously Portal islet transplantation and subcutaneous islet transplantation in the Device-Less sentinel spaces. Islets are maintained for a minimum of 6 hours up to 72 hours in supplemented CMRL1066-based media until the time of transplant. Concomitant to portal vein infusion, islet transplantation will occur in all four (4) DL sentinel spaces. To explant a unit, the Surgeon will make an incision and then carefully dissect the tissue engrafted around the transplant. The entire transplant site and any adherent tissue capsule can then be removed entirely from the pocket.

Treatment Group

Eligibility Criteria

• Age: 18 Years - 68 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Reduced awareness of hypoglycemia, as defined by the absence of adequate autonomic symptoms at plasma glucose levels \< 3.0 mmol/L, indicated by, 1 or more episodes of severe hypoglycemia requiring third-party assistance within 12 months, a Clarke score ≥4, HYPO score ≥1,000, lability index (LI) ≥400 or combined HYPO/LI \>400/\>300.
• Metabolic instability, characterized by erratic blood glucose levels that interfere with daily activities and/or 1 or more hospital visits for diabetic ketoacidosis over the last 12 months.
• Participants must be capable of understanding the purpose and risks of the study and must sign a statement of informed consent.

You may not qualify if:

• Significant skin conditions involving the area(s) targeted for implantation. Examples include but are not limited to recurrent boils/furuncles, extensive surgery or scarring, or lipodystrophy.
• History of enrollment in any other islet transplant trials and islet transplant under standard of care (at the discretion of the investigator).
• Severe co-existing cardiac disease, characterized by any one of these conditions: (a) recent (within the past 6months) myocardial infarction; (b) left ventricular ejection fraction \<30%; or (c) evidence of ischemia on functional cardiac exam.
• Active alcohol or substance abuse, including cigarette smoking (must be abstinent for 6 months prior to listing for transplant).
• 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).
• History of non-adherence to prescribed regimens.
• Active infection including Hepatitis C, Hepatitis B, HIV, or TB (subjects with a positive PPD performed within one year of enrollment, and no history of adequate chemoprophylaxis).
• Any history of, or current malignancies except squamous or basal skin cancer.
• BMI \> 35 kg/m2 at screening visit.
• Age less than 18 or greater than 68 years.
• Measured glomerular filtration rate (GFR) \<60 mL/min/1.73 m2.
• Presence or history of macroalbuminuria (\>300 mg/g creatinine).
• Clinical suspicion of nephritic (hematuria, active urinary sediment) or rapidly progressing renal impairment (e.g. Increase in serum creatinine of 25% within the last 3-6 months).
• Baseline Hb \< 105 g/L (\<10.5 g/dL) in women, or \< 120 g/L (\<12 g/dL) in men.
• Baseline screening liver function tests outside of normal range, with the exception of uncomplicated Gilbert's Syndrome. An initial LFT panel with any values \>1.5 times the upper limit of normal (ULN) will exclude a patient without a re-test; a re-test for any values between ULN and 1.5 times ULN should be made, and if the values remain elevated above normal limits, the patient will be excluded.

Sponsors & Collaborators

• University of Alberta: lead
• Juvenile Diabetes Research Foundation: collaborator

Study Sites (1)

University of Alberta Clinical Islet Transplant Program

Edmonton, Alberta, T6G 2E1, Canada

Location

Related Links

• related link

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• James Shapiro, MD, PhD

  University of Alberta

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Test a new biomedical intervention in a small group of people for the first time to evaluate safety (e.g. to determine a safe dosage range and to identify side effects)

Study Record Dates

• First Submitted: February 26, 2021
• First Posted: October 11, 2021
• Study Start: March 22, 2022
• Primary Completion: February 6, 2023
• Study Completion: March 11, 2025
• Last Updated: March 20, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)