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Device-Less Technique in Islet Transplantation

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ClinicalTrials.gov Identifier: NCT05073302
Recruitment Status : Not yet recruiting
First Posted : October 11, 2021
Last Update Posted : October 13, 2021
Sponsor:
Collaborator:
Juvenile Diabetes Research Foundation
Information provided by (Responsible Party):
University of Alberta

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.


Condition or disease Intervention/treatment Phase
Type 1 Diabetes Procedure: Implantation of Nylon catheter (Device-less sentinel unit) Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 5 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: 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)
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Trial Evaluating a Device-Less Technique in Islet Transplantation
Estimated Study Start Date : October 12, 2021
Estimated Primary Completion Date : November 24, 2024
Estimated Study Completion Date : November 24, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment Group
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)

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.





Primary Outcome Measures :
  1. Rate of Adverse Events/Serious Adverse Events [ Time Frame: 9 months ]
    Adverse Events/ Serious Adverse Event experienced by the participants in the study

  2. Rate of inflammation in the DL implant site [ Time Frame: 9 months ]
    Implant tolerability assessment


Secondary Outcome Measures :
  1. Probability of rejection or injury analyzed using the Molecular Microscope Diagnostic System (MMDx) system by measuring the expressions of all genes within the graft [ Time Frame: 9 months ]
    Molecular Microscope Diagnostic System (MMDx) of the explanted tissue

  2. Percentage of live cells measured by immunohistochemistry [ Time Frame: 9 months ]
  3. Presence of vascularization demonstrated by immunohistochemistry [ Time Frame: 9 months ]
  4. Presence of immune response demonstrated by immunohistochemistry [ Time Frame: 9 months ]
  5. Cellular composition demonstrated by immunohistochemistry [ Time Frame: 9 months ]


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Ages Eligible for Study:   18 Years to 68 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • Untreated proliferative retinopathy.
  • Positive pregnancy test, intent for future pregnancy or male subjects' intent to procreate, failure to follow effective contraceptive measures, or presently breast-feeding.
  • Evidence of significant sensitization on PRA (at the discretion of the investigator).
  • Insulin requirement >1.0 U/kg/day
  • HbA1C >12%.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05073302


Contacts
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Contact: Saira Qureshi, BSc 780-492-2709 citp@ualberta.ca
Contact: Parastoo Dinyari, BSc 780-492-1636 pdinyari@ualberta.ca

Locations
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Canada, Alberta
University of Alberta Clinical Islet Transplant Program
Edmonton, Alberta, Canada, T6G 2E1
Contact: Andrew J Shapiro, MD    (780) 492-3974    amjs68@gmail.com   
Contact: Rayna Bahneva    780-492-5727    bahneva@ualberta.ca   
Principal Investigator: Andrew J Shapiro, MD         
Sub-Investigator: Andrew Pepper, PhD         
Sub-Investigator: Peter Senior, MD         
Sponsors and Collaborators
University of Alberta
Juvenile Diabetes Research Foundation
Investigators
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Principal Investigator: James Shapiro, MD, PhD University of Alberta
Additional Information:
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Responsible Party: University of Alberta
ClinicalTrials.gov Identifier: NCT05073302    
Other Study ID Numbers: Pro00090942
First Posted: October 11, 2021    Key Record Dates
Last Update Posted: October 13, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Alberta:
Device-less, Islet Transplantation
Additional relevant MeSH terms:
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Diabetes Mellitus, Type 1
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases