A Phase I/II Study of the Safety and Efficacy of Sernova's Cell PouchTM for Therapeutic Islet Transplantation

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2012 by University of Alberta
Sponsor:
Collaborator:
Sernova Corp
Information provided by (Responsible Party):
James Shapiro, University of Alberta
ClinicalTrials.gov Identifier:
NCT01652911
First received: July 12, 2012
Last updated: July 30, 2012
Last verified: July 2012
  Purpose

This is an open-label, single arm, non-randomized safety and efficacy study, where participants with Type-1 diabetes will receive the Sernova Cell Pouch™ implanted in the subcutaneous site, two to approximately twelve weeks prior to transplantation of islets into the Cell Pouch™.

The primary objective of this study is to assess the safety of the Sernova Cell Pouch™ in adult participants with Type-1 diabetes receiving islet transplantation for the first time.

Secondary objectives are the following:

  1. To determine the proportion of subjects implanted with the Cell Pouch™ and transplanted with islets into the Cell Pouch™ who achieve and maintain insulin independence after islet transplantation.
  2. To obtain preliminary data on the efficacy of the Cell Pouch™ to maintain adequate immunological protection against both allo- and autoimmunity of islet transplant recipients.
  3. To determine through retrospective analysis comparative metabolic function and engraftment efficiency using patients undergoing standard intraportal islet transplantation under the current alemtuzumab standard of care protocol.

Condition Intervention Phase
Type I Diabetes
Device: Sernova Cell Pouch
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of the Safety and Efficacy of Sernova's Cell PouchTM for Therapeutic Islet Transplantation

Resource links provided by NLM:


Further study details as provided by University of Alberta:

Primary Outcome Measures:
  • To assess the safety of the Sernova Cell Pouch™ in adult participants with Type-1 diabetes receiving islet transplantation for the first time. [ Time Frame: 3 years post-initial Cell Pouch™ implant. ] [ Designated as safety issue: Yes ]
    A tracking log will document adverse events with grading classification as per protocol. For the primary objective endpoint, safety will be assessed following initial Cell Pouch implantation, at the time of islet transplantation, and approximately one month following the initial islet transplantation. Safety will further be assessed at approximately three, six, nine and twelve months and then yearly thereafter.


Secondary Outcome Measures:
  • To determine the proportion of subjects implanted with the Cell Pouch™ and transplanted with islets into the Cell Pouch™ who achieve insulin independence after islet transplantation. [ Time Frame: 3 years post-initial Cell Pouch™ implant. ] [ Designated as safety issue: Yes ]
    The proportion of study participants achieving and maintaining insulin independence (c-peptide, HbA1c level) with good glycemic control (blood sugar measurement) at 1, 3, 6 and 12 months and yearly thereafter.

  • To obtain preliminary data on the efficacy of the Cell Pouch™. [ Time Frame: 3 years post-initial CellPouch™ ] [ Designated as safety issue: Yes ]
    The efficacy analysis will compare observed proportion of subjects who become insulin independent at the end of month 3 following the completed islet transplant. The outcomes will also be analyzed at 1, 6 and 12 months and then yearly thereafter.


Estimated Enrollment: 20
Study Start Date: June 2012
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Intervention Details:
    Device: Sernova Cell Pouch
    The Cell Pouch™ is an implantable medical device for transplantation of donor islets for Type-1 diabetes as an alternative to the current standard of care using intraportal delivery of islets.
  Eligibility

Ages Eligible for Study:   18 Years to 68 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

To be eligible the participant must have had T1DM for more than 5 years, complicated by at least 1 of the following situations that persist despite intensive insulin management efforts:

  1. Reduced awareness of hypoglycemia, as defined by the absence of adequate autonomic symptoms at plasma glucose levels < 3.0 mmol/L, indicated by, 2 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
  2. Metabolic instability, characterized by erratic blood glucose levels that interfere with daily activities and or 2 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:

  1. Severe co-existing cardiac disease, characterized by any one of these conditions: (a) recent myocardial infarction (within past 6 months); (b) left ventricular ejection fraction <30%; or (c) evidence of ischemia on functional cardiac exam.
  2. Active alcohol or substance abuse, to include cigarette smoking (must be abstinent for 6 months prior to transplant).
  3. 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).
  4. History of non-adherence to prescribed regimens.
  5. Active infection including Hepatitis C, Hepatitis B, HIV, TB (subjects with a positive PPD performed within one year of enrollment, and no history of adequate chemoprophylaxis).
  6. Any history of or current malignancies except squamous or basal skin cancer.
  7. BMI > 35 kg/m2 at screening visit.
  8. Age less than 18 or greater than 68 years.
  9. Measured glomerular filtration rate (GFR) <60 mL/min/1.73 m2.
  10. Presence or history of macroalbuminuria (>300 mg/g creatinine).
  11. 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).
  12. Baseline Hb < 105g/L in women, or < 120 g/L in men.
  13. 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.
  14. Untreated proliferative retinopathy.
  15. Positive pregnancy test, intent for future pregnancy or male subjects' intent to procreate, failure to follow effective contraceptive measures, or presently breast feeding.
  16. Previous transplant or evidence of significant sensitization on PRA (at the discretion of the investigator).
  17. Insulin requirement >1.0 U/kg/day
  18. HbA1C >12%.
  19. Uncontrolled hyperlipidemia [fasting LDL cholesterol > 3.4 mmol/L, treated or untreated; and/or fasting triglycerides > 2.3 mmol/L].
  20. Under treatment for a medical condition requiring chronic use of steroids.
  21. Use of coumadin or other anticoagulant therapy (except aspirin) or subject with PT INR > 1.5.
  22. Untreated Celiac disease.
  23. Patients with Graves disease will be excluded unless previously adequately treated with radioiodine ablative therapy.
  24. Any medical condition that, in the opinion of the clinical investigator, will interfere with the safe participation in the trial.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01652911

Contacts
Contact: Andrew Malcolm, PhD 780-407-6952 andrew.malcolm@ualberta.ca
Contact: Parastoo Dinyari, BSc 780-407-3904 parastoo@islet.ca

Locations
Canada, Alberta
University of Alberta - Clinical Islet Transplant Program Recruiting
Edmonton, Alberta, Canada, T6G 2C8
Principal Investigator: James Shapiro, MD, PhD         
Sponsors and Collaborators
University of Alberta
Sernova Corp
Investigators
Principal Investigator: James Shapiro, MD, PhD University of Alberta
  More Information

Additional Information:
No publications provided

Responsible Party: James Shapiro, Director, Clinical Islet Transplant Program, University of Alberta
ClinicalTrials.gov Identifier: NCT01652911     History of Changes
Other Study ID Numbers: Pro00028097
Study First Received: July 12, 2012
Last Updated: July 30, 2012
Health Authority: Canada: Health Canada

Keywords provided by University of Alberta:
Islet Transplantation
Cell Pouch

Additional relevant MeSH terms:
Diabetes Mellitus, Type 1
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on July 26, 2014