Questa pagina è stata tradotta automaticamente e l'accuratezza della traduzione non è garantita. Si prega di fare riferimento al Versione inglese per un testo di partenza.

LEA29Y (Belatacept) Emory Edmonton Protocol (LEEP)

9 marzo 2016 aggiornato da: National Institute of Allergy and Infectious Diseases (NIAID)

Islet Transplantation in Type I Diabetes With LEA29Y (Belatacept) Maintenance Therapy (CIT-04)

Type 1 diabetes is an autoimmune disease in which the insulin-producing pancreatic beta cells are destroyed, resulting in poor blood sugar control. The purpose of this study is to determine the safety and effectiveness of islet transplantation using a steroid-free, calcineurin-inhibitor-free belatacept based immunosuppressive medication, for treating type 1 diabetes in individuals experiencing hypoglycemia unawareness and severe hypoglycemic episodes.

Panoramica dello studio

Stato

Completato

Condizioni

Intervento / Trattamento

Descrizione dettagliata

Type 1 diabetes is commonly treated with the administration of insulin, either by multiple insulin injections or by a continuous supply of insulin through a wearable pump. Insulin therapy allows long-term survival in individuals with type 1 diabetes; however, it does not guarantee constant normal blood sugar control. Because of this, long-term type 1 diabetic survivors often develop vascular complications, such as diabetic retinopathy, an eye disease that can cause poor vision and blindness, and diabetic nephropathy, a kidney disease that can lead to kidney failure. Some individuals with type 1 diabetes develop hypoglycemia unawareness, a life-threatening condition that is not easily treatable with medication and is characterized by reduced or absent warning signals for hypoglycemia. For such individuals, transplantation of pancreatic islets is a possible treatment option. Unfortunately, insulin independence among islet transplant recipients tends to decline over time. New strategies aimed at promoting engraftment of transplanted islets are needed to improve the clinical outcomes associated with this procedure. The purpose of this study is determine the safety and efficacy of islet transplantation, when combined with an immunosuppressive medication regimen containing belatacept, for treating type 1 diabetes in individuals experiencing hypoglycemia unawareness and severe hypoglycemic episodes. This study will also seek to improve the understanding of determinants of success and failure of islet transplants for type 1 diabetes.

Eligible participants will be randomly assigned to this study or a site-specific Phase 3 islet transplantation study (CIT-07). Participants in this study will receive up to three separate islet transplants and a regimen of immunosuppressive medications consisting of belatacept, basiliximab (an IL-2 monoclonal antibody receptor blocker), and mycophenolate mofetil. Participants will begin receiving all three drugs on the day of the first islet transplant. Belatacept will also be administered again on Days 4, 14, 28, 56, and 84 post-transplant and then every 4 weeks for the duration of the study.

If the participant receives daclizumab, it will also be given again on Days 14, 28, 42, and 56 post-transplant; if the participant receives basiliximab, it will also be given again on Day 4 post-transplant. Mycophenolate mofetil will also be given for the duration of the study.

Transplantations will involve an inpatient hospital stay and intraportal infusion of islet cells. Participants who do not achieve or maintain insulin independence by Day 75 post-transplant will be considered for a second islet transplant. Participants who remain dependent on insulin for longer than 1 month after the second transplant and who show partial graft function will be considered for a third islet transplant. Participants who do not meet the criteria for a subsequent transplant and do not have a functioning graft will enter a reduced follow-up period.

There will be up to 25 study visits following each transplant. A physical exam, review of adverse events, and blood collection will occur at most visits. A chest x-ray, abdominal ultrasound, electrocardiogram, quality of life questionnaires, urine collection, and more extensive blood testing will occur at some visits. Participants will also test their own blood glucose levels at least five times per day throughout the study. A 24-month follow-up period will take place after the participant's last transplant.

Tipo di studio

Interventistico

Iscrizione (Effettivo)

10

Fase

  • Fase 2

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G028
        • University of Alberta
  • Stati Uniti
    • Georgia
      • Atlanta, Georgia, Stati Uniti, 30322
        • Emory University

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

Da 18 anni a 65 anni (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

Inclusion Criteria:

  • Mentally stable and able to comply with study procedures
  • Clinical history compatible with type 1 diabetes with onset of disease at less than 40 years of age, insulin dependence for at least 5 years at study entry, and a sum of age and insulin dependent diabetes duration of at least 28
  • Absent stimulated C-peptide (less than 0.3 ng/mL) 60 and 90 minutes post-mixed-meal tolerance test

  • Involvement of intensive diabetes management, defined as:

    1. Self-monitoring of glucose no less than a mean of three times each day averaged over each week
    2. Three or more insulin injections each day or insulin pump therapy
    3. Under the care of an endocrinologist, diabetologist, or diabetes specialist with at least three clinical evaluations during the past 12 months prior to study enrollment
  • At least one episode of severe hypoglycemia, defined as an event with one of the following symptoms: memory loss; confusion; uncontrollable behavior; irrational behavior; unusual difficulty in awakening; suspected seizure; seizure; loss of consciousness; or visual symptoms, in which the participant was unable to treat him/herself and which was associated with either a blood glucose level less than 54 mg/dL or prompt recovery after oral carbohydrate, intravenous glucose, or glucagons in the 12 months prior to study enrollment
  • Reduced awareness of hypoglycemia. More information about this criterion is in the protocol.

Exclusion Criteria:

  • Body mass index (BMI) greater than 30 kg/m^2 or weight less than or equal to 50 kg (110 lbs)
  • Insulin requirement of more than 1.0 IU/kg/day or less than 15 U/day
  • HbA1c greater than 10%
  • Untreated proliferative diabetic retinopathy
  • Systolic blood pressure higher than 160 mmHg or diastolic blood pressure higher than 100 mmHg
  • Measured glomerular filtration rate using iohexol of less than 80 mL/min/1.73m^2.
  • Presence or history of macroalbuminuria (greater than 300 mg/g creatinine)
  • Presence or history of panel-reactive anti-Histocompatibility Antigen (HLA) antibody levels greater than background by flow cytometry. More information about this criterion is in the protocol.
  • Pregnant, breastfeeding, or unwilling to use effective contraception throughout the study and 4 months after study completion
  • All women more than 35 years and women of any age who have first degree relatives with a history of breast carcinoma or who have other risk factors of breast carcinoma. More information about this criterion is in the study protocol.
  • Active infection, including hepatitis B, hepatitis C, human immunodeficiency virus (HIV). Presence or history of tuberculosis. More information about these criteria is in the protocol.
  • Negative for Epstein-Barr virus (EBV) by anti-viral capsid antigen (VCA) IgG (EBV VCA-IgG) determination
  • Invasive aspergillus, histoplasmosis, or coccidioidomycosis infection in the past year
  • History of malignancy except for completely resected squamous or basal cell carcinoma of the skin
  • Known active alcohol or substance abuse
  • Baseline Hgb below the lower limits of normal, lymphopenia, neutropenia, or thrombocytopenia
  • History of Factor V deficiency
  • Any coagulopathy or medical condition requiring long-term anticoagulant therapy after transplantation or individuals with an international normalized ratio (INR) greater than 1.5.

  • Severe coexisting cardiac disease, defined as:

    1. Heart attack within the last 6 months
    2. Evidence of ischemia on functional heart exam within the year prior to study entry
    3. Left ventricular ejection fraction less than 30%
  • Persistent elevation of liver function tests at study entry
  • Symptomatic cholecystolithiasis
  • Acute or chronic pancreatitis
  • Symptomatic peptic ulcer disease
  • Severe unremitting diarrhea, vomiting, or other gastrointestinal disorders that could interfere with the ability to absorb oral medications
  • Hyperlipidemia despite medical therapy, defined as fasting LDL cholesterol greater than 130 mg/dL and/or fasting triglycerides greater than 200 mg/dL
  • Currently receiving treatment for a medical condition that requires chronic use of systemic steroids except for the use of 5 mg or less of prednisone daily, or an equivalent dose of hydrocortisone, for physiological replacement only
  • Treatment with any antidiabetic medication other than insulin within the past 4 weeks
  • Previous receipt of belatacept
  • Use of any investigational agents within the past 4 weeks
  • Received a live attenuated vaccine(s) within the past 2 months

  • Any medical condition that, in the opinion of the investigator, might interfere with safe participation in the trial

    • Treatment with any immunosuppressive regimen at the time of enrollment.
    • A previous islet transplant.
    • A previous pancreas transplant, unless the graft failed within the first week due to thrombosis, followed by pancreatectomy and the transplant occurred more than 6 months prior to enrollment.
  • Known hypersensitivity to mycophenolate mofetil or any of its components
  • Imprisonment or involuntary incarceration for treatment of either a psychiatric or physical illness
  • Rare hereditary deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) such as Lesch-Nyhan and Kelly-Seegmiller syndrome
  • Dietary restriction of phenylalanine

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: N / A
  • Modello interventistico: Assegnazione di gruppo singolo
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: Allogeneic Pancreatic Islet Cells
Participants will receive up to three islet transplantations and continuous immunosuppressive therapy including belatacept
Biologico: Allogeneic Pancreatic Islet Cells
Transplant of islet cells from a healthy pancreas. A dose of at least 5,000 Islet Equivalents (IEQ)/kg recipient body weight (BW) infused intraportally for the first transplant, and at least 4,000 IEQ/kg recipient BW infused intraportally for subsequent transplants.
Biologico: Belatacept
Belatacept is an inhibitor of the 2 signals that stimulate T-cells. Subjects will receive NULOJIX® (belatacept)10mg/kg through a peripheral vein on Day 0 and post-operative days 4, 14, 28, 56, 84. After Day 84 subjects will receive belatacept at a maintenance dose of 5 mg/kg every 4 weeks for the duration of study follow-up (2 years after the final islet transplant). Infusion doses will be based upon the subject's actual body weight at study Day 0 and will not be modified during the course of the study unless there is a change in body weight plus or minus 10% of Day 0 body weight.
Altri nomi:
  • NUJOLIX
Biologico: Basiliximab
Immunosuppressive medication for prophylaxis of acute transplant rejection. Two Intravenous (IV) doses of basiliximab, a monoclonal antibody Interleukin 2 (IL-2) receptor blocker, will be given with the first and second (if necessary) transplants. The first dose will be 20 mg and will be given within two hours prior to islet transplant on the day of islet transplantation. The second 20 mg dose will be given on Day 4 after the transplant.If a third islet transplant is deemed necessary and performed more than 70 days after the second transplant, both doses of basiliximab will be repeated. No additional doses of basiliximab will be given with a third transplant that is performed between 30 and 70 days after the second transplant.
Altri nomi:
  • Simuletto
Droga: Mycophenolate Mofetil
Maintenance immunosuppressive therapy. Subjects will receive mycophenolate mofetil starting immediately pre-transplant on Day 0 at a dose of 1g orally twice a day for the duration of study follow-up (2 years after the final islet transplant).
Altri nomi:
  • Cellcept
Droga: Tacrolimus
Tacrolimus may be used only as a supplement to maintenance mycophenolate mofetil (MMF) in those cases where the trough level is below the therapeutic range. Tacrolimus will be administered orally twice a day to maintain trough levels of 3-5 ng/mL. Generic equivalents of Prograf® will not be permitted.
Altri nomi:
  • Prograf
Procedura: Intraportal infusion of islet cells
The infusion of allogeneic pancreatic islet cells (islet transplant[s]) will occur intraportally.

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Lasso di tempo
Proportion of subjects with insulin independence
Lasso di tempo: 75 days after first islet transplant
75 days after first islet transplant

Misure di risultato secondarie

Misura del risultato
Lasso di tempo
Proportion of subjects with an HbA1c <7.0% AND free of severe hypoglycemic events
Lasso di tempo: from Day 28 to Day 365, inclusive, after the first islet transplant
from Day 28 to Day 365, inclusive, after the first islet transplant
Proportion of subjects with an HbA1c <7.0% AND free of severe hypoglycemic events
Lasso di tempo: from Day 28 to Day 365, inclusive, after the final islet transplant
from Day 28 to Day 365, inclusive, after the final islet transplant
Percent reduction in insulin requirements, HbA1c, Mean amplitude of glycemic excursions (MAGE), Glycemic lability index (LI), Ryan hypoglycemia severity (HYPO) score
Lasso di tempo: 75 Days after first and final islet transplant
75 Days after first and final islet transplant
Basal (fasting) and 90-min glucose and C-peptide derived from the mixed-meal tolerance test (MMTT), beta-score, C-peptide: glucose-creatinine ration, acute insulin response to glucose
Lasso di tempo: 75 Days after first and final islet transplant
75 Days after first and final islet transplant
Insulin sensitivity and disposition index derived from the insulin-modified frequently-sampled intravenous glucose tolerance test (FSIGT) test
Lasso di tempo: 75 days after first and final islet transplant
75 days after first and final islet transplant
Glucose variability and hypoglycemia duration, derived from the continuous glucose monitoring system (CGMS), quality of life (QOL) measures
Lasso di tempo: 75 days after first and final islet transplant
75 days after first and final islet transplant
Percent reduction in insulin requirements, HbA1c, Mean amplitude of glycemic excursions (MAGE), Glycemic lability index (LI), Clarke Score, Ryan hypoglycemia severity (HYPO) score
Lasso di tempo: 365 days after first and final islet transplant
365 days after first and final islet transplant
Basal (fasting) and 90-min glucose and C-peptide derived from the mixed-meal tolerance test (MMTT), beta-score, C-peptide: glucose-creatinine ratio
Lasso di tempo: 365 days after first and final islet transplant
365 days after first and final islet transplant
Insulin sensitivity and disposition index derived from the insulin-modified frequently-sampled intravenous glucose tolerance test (FSIGT) test
Lasso di tempo: 365 days after first and final islet transplant
365 days after first and final islet transplant
Glucose variability and hypoglycemia duration, derived from the continuous glucose monitoring system (CGMS), quality of life (QOL) measures
Lasso di tempo: 365 days after first and final islet transplant
365 days after first and final islet transplant
Proportion of participants receiving a second or third islet transplant
Lasso di tempo: 365 days after first and final islet transplant
365 days after first and final islet transplant
Rate of favorable outcome at each center preparing islets (rate of subjects with an HbA1c < 7.0% and free of severe hypoglycemic events)
Lasso di tempo: 365 days after first and final islet transplant
365 days after first and final islet transplant
Incidence and severity of adverse events related to the islet transplant procedure
Lasso di tempo: 75 days following each transplant and 365 days following the first and final islet transplant
75 days following each transplant and 365 days following the first and final islet transplant
Incidence and severity of adverse events related to immunosuppression therapy
Lasso di tempo: 75 days following each transplant and 365 days following the first and final islet transplant
75 days following each transplant and 365 days following the first and final islet transplant
Incidence of change in the immunosuppression drug regimen
Lasso di tempo: 75 days following each transplant and 365 days following the first and final islet transplant
75 days following each transplant and 365 days following the first and final islet transplant
Incidence of immune sensitization defined by presence of Histocompatibility Antigen (HLA) antibodies absent prior to transplantation
Lasso di tempo: 75 days following each transplant and 365 days following the first and final islet transplant
75 days following each transplant and 365 days following the first and final islet transplant
Incidence of worsening retinopathy
Lasso di tempo: 365 days following the first islet transplant
365 days following the first islet transplant
Percent reduction in insulin requirements, HbA1c, Mean amplitude of glycemic excursions (MAGE), Glycemic lability index (LI), Clarke Score, Ryan hypoglycemia severity (HYPO) score
Lasso di tempo: From 75 days to 365 days after final islet transplant
From 75 days to 365 days after final islet transplant
Basal (fasting) and 90-min glucose and C-peptide derived from the mixed-meal tolerance test (MMTT), beta-score, C-peptide: glucose-creatinine ratio
Lasso di tempo: From 75 days to 365 days after final islet transplant
From 75 days to 365 days after final islet transplant
Insulin sensitivity and disposition index derived from the insulin-modified frequently-sampled intravenous glucose tolerance test (FSIGT) test
Lasso di tempo: From 75 days to 365 days after final islet transplant
From 75 days to 365 days after final islet transplant
Glucose variability and hypoglycemia duration, derived from the continuous glucose monitoring system (CGMS), quality of life (QOL) measures
Lasso di tempo: From 75 days to 365 days after final islet transplant
From 75 days to 365 days after final islet transplant
Proportion of participants receiving a second or third islet transplant
Lasso di tempo: From 75 days to 365 days after final islet transplant
From 75 days to 365 days after final islet transplant
Rate of favorable outcome at each center preparing islets (rate of subjects with an HbA1c < 7.0% and free of severe hypoglycemic events)
Lasso di tempo: From 75 days to 365 days after final islet transplant
From 75 days to 365 days after final islet transplant
Percent reduction in insulin requirements, number of severe hypoglycemic events from 28 days to 2 years, HbA1c, Clarke Score
Lasso di tempo: Two years after final islet transplant
Two years after final islet transplant
Basal (fasting) and 90-min glucose and C-peptide derived from the mixed-meal tolerance test (MMTT), beta-score, C-peptide
Lasso di tempo: Two years after final islet transplant
Two years after final islet transplant
Glucose variability and hypoglycemia duration, derived from the continuous glucose monitoring system (CGMS), quality of life (QOL) measures
Lasso di tempo: Two years after final islet transplant
Two years after final islet transplant
Safety associated with conventional immunosuppression
Lasso di tempo: Two years after final islet transplant
Two years after final islet transplant
Renal function as measured by serum creatinine, glomerular filtration rate (GFR) and other relevant laboratory parameters
Lasso di tempo: Two years after final islet transplant
Two years after final islet transplant
Lipid profiles (triglycerides, total cholesterol, LDL cholesterol, HDL cholesterol)
Lasso di tempo: Two years after final islet transplant
Two years after final islet transplant

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaboratori

Clinical Islet Transplantation Consortium

Investigatori

  • Cattedra di studio: A.M. James Shapiro, MD, PhD, Clinical Islet Transplant Program, University of Alberta
  • Cattedra di studio: Nicole Turgeon, MD, Clinical Islet Transplant Program, Emory University

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Pubblicazioni generali

Collegamenti utili

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio

1 ottobre 2008

Completamento primario (Effettivo)

1 aprile 2012

Completamento dello studio (Effettivo)

1 aprile 2013

Date di iscrizione allo studio

Primo inviato

1 maggio 2007

Primo inviato che soddisfa i criteri di controllo qualità

1 maggio 2007

Primo Inserito (Stima)

2 maggio 2007

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Stima)

7 aprile 2016

Ultimo aggiornamento inviato che soddisfa i criteri QC

9 marzo 2016

Ultimo verificato

1 marzo 2016

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • DAIT CIT-04

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

Cerca prove simili

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

CROs by country

CROs in Azerbaijan

Condizioni

Malattie rare

Interventi farmacologici

Supplementi dietetici

Sponsor / Collaboratori

Sedi

Sottoscrivi