Omental Islet Transplant

NCT02821026 | Completed Phase 1 DMC

• 1 other identifier: Pro00058260
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

Islet transplantation is a relatively new procedure used in people with difficult to control Type 1 diabetes. Insulin producing cells (islets) are isolated from a pancreas of a deceased organ donor. After the cells are carefully prepared, the islets are transplanted into patient's body. These transplanted islets may produce insulin for the patient. Patient may be able to reduce or eliminate the need for insulin injections for an unknown period of time. Patients who receive an islet transplant may need to stay on powerful immunosuppressive drugs for as long as the islets remain alive and working. These drugs help to prevent the immune system from attacking the transplanted islets. Under current standard of care procedure, islets are transplanted into patient's liver. The investigators have learned that some of these cells do not survive the current procedure and are lost around the time of transplant. Therefore in this study, the investigators are studying a new transplant procedure that may help prevent this islet cell loss. The new procedure involves transplanting the islets into an omental pouch instead of into the liver. The omentum is a large apron-like fold of membrane inside the abdomen that drapes over the intestines. This study will test to see if omental islet transplantation is safe and effective. Standard immunosuppressive medicines (anti-thymocyte globulin, tacrolimus, mycophenolic acid, sirolimus, etanercept) will be used in this study to prevent rejection of the islets. This study is a collaborative research with the University of Miami, and the same study protocol has been in use over there. Recruitment in Edmonton will continue until all subjects \[N=6\] needed for the study are transplanted. All subjects in this study will receive islet transplants using the study procedure.

Conditions

Type 1 Diabetes

Outcome Measures

Primary Outcomes (2)

• The incidence of Serious Adverse Events

  2 years following islet transplant

• The proportion of subjects with HbA1c ≤ 6.5% at 1 year AND free of severe hypoglycemic events from Day 28 to Day 365, inclusive, after the islet transplant

  From Day 28 to Day 365 inclusive after islet transplant

Secondary Outcomes (60)

• The percent reduction in insulin requirements at Day 75±7 after islet transplant

  Baseline and Day 75±7 after islet transplant

• The percent reduction in insulin requirements at Day 365±14 after islet transplant

  Baseline and Day 365±14 after islet transplant

• The percent reduction in insulin requirements at Day 730±14 after islet transplant

  Baseline and Day 730±14 after islet transplant

• Change from baseline in HbA1c at Day 75±7 after islet transplant

  Baseline and Day 75±7 after islet transplant

• Change from baseline in HbA1c at Day 365±14 after islet transplant

  Baseline and Day 365±14 after islet transplant

Study Arms (1)

Omental islet transplant

EXPERIMENTAL

At the time a suitable islet preparation becomes available, the patient will receive allogeneic islet cells placed in an omental pouch. Islet transplant will be performed under Anti-Thymocyte Globulin induction immunosuppression (5 doses, day -2 prior to transplant to day 2 post-transplant). Maintenance mycophenolate mofetil therapy (1-2 g/day as BID dosing) will be started on Day -1 pre-transplant. Tacrolimus will be administered orally twice daily on Day 1 post-transplant to maintain a trough level of 10-12 ng/mL for 3 months, then 6-10 ng/mL thereafter. Etanercept will be given IV before the islet transplant (50 mg), and then at 25 mg (subcutaneously) on POD +3, +7 and +10. Sirolimus will be used in case of tacrolimus or/and mycophenolate mofetil intolerance.

Procedure: Omental Islet transplant; Drug: Anti-Thymocyte Globulin; Drug: Mycophenolate mofetil; Drug: Tacrolimus; Drug: Etanercept; Drug: Sirolimus

Interventions

Omental Islet transplant PROCEDURE

The intervention is transplanting the islets into an omental pouch instead of into the liver. The omentum is a large apron-like fold of membrane inside the abdomen that drapes over the intestines. This study will test to see if omental islet transplantation is safe and effective. Standard immunosuppressive medicines (anti-thymocyte globulin, tacrolimus, mycophenolic acid, sirolimus, etanercept) will be used in this study to prevent rejection of the islets.

Omental islet transplant

Anti-Thymocyte Globulin DRUG

Also known as: Thymoglobulin®

Omental islet transplant

Mycophenolate mofetil DRUG

Omental islet transplant

Tacrolimus DRUG

Omental islet transplant

Etanercept DRUG

Omental islet transplant

Sirolimus DRUG

Sirolimus will be used in case of tacrolimus or/and mycophenolate mofetil intolerance.

Omental islet transplant

Eligibility Criteria

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

You may qualify if:

• Male and female patients age 18 to 65 years of age.
• Ability to provide written informed consent.
• Mentally stable and able to comply with the procedures of the study protocol.
• Clinical history compatible with T1D with onset of disease at \<40 years of age, insulin-dependence for \> 5 years at the time of enrollment, and a sum of subject age and insulin-dependent diabetes duration of ≥28.
• Absent stimulated c-peptide (\<0.3 ng/mL) in response to a MMTT (Boost® 6 mL/kg body weight to a maximum of 360 mL; another product with equivalent caloric and nutrient content may be substituted for Boost®) measured at 60 and 90 min after the start of consumption.
• Involvement in intensive diabetes management, defined as self-monitoring of glucose values no less than a mean of three times each day averaged over each week and by the administration of three or more insulin injections each day or insulin pump therapy. Such management must be under the direction of an endocrinologist, diabetologist, or diabetes specialist, with at least 3 clinical evaluations during the 12 months prior to study enrollment.
• At least one episode of severe hypoglycemia in the 12 months prior to study enrollment.
• Reduced awareness of hypoglycemia as defined by a Clarke score of 4 or more OR A HYPO score greater than or equal to the 90th percentile (1047) during the screening period; OR Marked glycemic lability characterized by wide swings in blood glucose (BG) despite optimal diabetes therapy and defined by an LI score greater than or equal to the 90th percentile (43 mmol/L2/h·wk-1) during the screening period; OR A composite of a Clarke score of 3 or less and a HYPO score greater than or equal to the 75th percentile (423) and a LI greater than or equal to the 75th percentile (329) during the screening period.

You may not qualify if:

• Body Mass Index (BMI) \>30 kg/m2 or patient weight ≤50 kg.
• Insulin requirement of \>1.0 IU/kg/day or \<15 U/day.
• HbA1c \>10%.
• Untreated proliferative diabetic retinopathy.
• Blood Pressure: systolic blood pressure (SBP) \>160 mmHg or diastolic blood pressure (DBP) \>100 mmHg.
• Measured glomerular filtration rate \<80 mL/min/1.73 m2 calculated using the subject's measured serum creatinine and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation1 or Modification of Diet in Renal Disease \[MDRD\] study estimation formula). Strict vegetarians (vegans) with a calculated GFR \<70 mL/min/1.73m2 are excluded. The absolute (raw) GFR value will be used for subjects with body surface areas \>1.73m2
• Presence or history of macroalbuminuria (\>300mg/g creatinine).
• Presence or history of panel-reactive anti-HLA antibodies above background by flow cytometry.
• For female subjects: Serum or urine Positive pregnancy test, presently breast-feeding, or unwillingness to use effective contraceptive measures for the duration of the study and 4 months after discontinuation. For male subjects: intent to procreate during the duration of the study or within 4 months after discontinuation or unwillingness to use effective measures of contraception. If sexually active, subject must use at least two medically accepted methods of birth control from the following list: oral contraceptives, Norplant®, Depo-Provera®, intrauterine device (IUD), barrier devices with spermicide. Condoms used alone are not acceptable. Instead of the male condom, it is acceptable to use a female condom with one of the other methods for women listed above.
• Presence or history of active infection including hepatitis B, hepatitis C, HIV, or tuberculosis (TB) Subjects with laboratory evidence of active infection are excluded even in the absence of clinical evidence of active infection.
• Negative screen for Epstein-Barr Virus (EBV) by IgG determination.
• Invasive aspergillus, histoplasmosis, and coccidioidomycosis infection within one year prior to study enrollment.
• Any history of malignancy except for completely resected squamous or basal cell carcinoma of the skin.
• Known active alcohol or substance abuse.
• Baseline Hb below the lower limits of normal at the local laboratory; lymphopenia (\<1,000/µL), neutropenia (\<1,500/µL), or thrombocytopenia (platelets \<100,000/µL). Participants with lymphopenia are allowed if the investigator determines there is no additional risk and obtain clearance from a hematologist.

Sponsors & Collaborators

• University of Alberta: lead

Study Sites (1)

Clinical Islet Transplant Program

Edmonton, Alberta, T6G2C8, Canada

Location

Related Links

• Clinical Islet Transplant Program

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Antilymphocyte Serum; thymoglobulin; Mycophenolic Acid; Tacrolimus; Etanercept; Sirolimus

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Macrolides; Lactones; Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Immunoglobulin Constant Regions; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins

Study Officials

• James Shapiro, MD

  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

Study Record Dates

• First Submitted: June 20, 2016
• First Posted: July 1, 2016
• Study Start: May 1, 2016
• Primary Completion: November 13, 2019
• Study Completion: November 13, 2019
• Last Updated: May 9, 2022

Record last verified: 2019-11

Locations

CA (1)