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Islet Transplantation in Type 1 Diabetes

11 lipca 2019 zaktualizowane przez: National Institute of Allergy and Infectious Diseases (NIAID)
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, combined with immunosuppressive medications, for treating type 1 diabetes in individuals experiencing hypoglycemia unawareness and severe hypoglycemic episodes.

Przegląd badań

Status

Zakończony

Warunki

Interwencja / Leczenie

Szczegółowy opis

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, 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 2 islet transplantation study. Participants in this study will receive up to three separate islet transplants and a regimen of immunosuppressive medications consisting of antithymocyte globulin (ATG), sirolimus, and low-dose tacrolimus.

Transplantations will involve an inpatient hospital stay and infusion of islets into a branch of the portal vein. 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. Basiliximab will be used in place of ATG for the second and third transplants, if they are necessary. 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 19 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 glomerular filtrating rate (GFR) 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.

Typ studiów

Interwencyjne

Zapisy (Rzeczywisty)

48

Faza

  • Faza 3

Kontakty i lokalizacje

Ta sekcja zawiera dane kontaktowe osób prowadzących badanie oraz informacje o tym, gdzie badanie jest przeprowadzane.

Lokalizacje studiów

  • Kanada
    • Alberta
      • Edmonton, Alberta, Kanada, T6G028
        • University of Alberta
  • Stany Zjednoczone
    • California
      • San Francisco, California, Stany Zjednoczone, 94143
        • University of Callifornia, San Francisco
    • Florida
      • Miami, Florida, Stany Zjednoczone, 33136
        • University of Miami
    • Georgia
      • Atlanta, Georgia, Stany Zjednoczone, 30322
        • Emory University
    • Illinois
      • Chicago, Illinois, Stany Zjednoczone, 60611
        • Northwestern University
      • Chicago, Illinois, Stany Zjednoczone, 60612
        • University of Illinois, Chicago
    • Minnesota
      • Minneapolis, Minnesota, Stany Zjednoczone, 55455
        • University of Minnesota
    • Pennsylvania
      • Philadelphia, Pennsylvania, Stany Zjednoczone, 19104
        • University of Pennsylvania

Kryteria uczestnictwa

Badacze szukają osób, które pasują do określonego opisu, zwanego kryteriami kwalifikacyjnymi. Niektóre przykłady tych kryteriów to ogólny stan zdrowia danej osoby lub wcześniejsze leczenie.

Kryteria kwalifikacji

Wiek uprawniający do nauki

18 lat do 65 lat (Dorosły, Starszy dorosły)

Akceptuje zdrowych ochotników

Nie

Płeć kwalifikująca się do nauki

Wszystko

Opis

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 values no less than a mean of three times each day averaged over each week
    2. Administration of three or more insulin injections each day or insulin pump therapy
    3. Under the direction 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 in the past 12 months, 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, compatible with hypoglycemia in which the individual required assistance of another subject was unable to treat him/herself person and which was associated with either a blood glucose level less than 54 mg/dl or prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration in the 12 months prior to study enrollment
  • Reduced awareness of hypoglycemia. More information about this criterion, including specific definition of hypoglycemia unawareness, is in the protocol.

Exclusion Criteria:

  • Body mass index (BMI) greater than 30 kg/m2 or weight less than or equal to 50 kg
  • 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/1.73mm2. More information about this criterion is in the protocol.
  • Presence or history of macroalbuminuria (greater than 300 mg/g creatinine)
  • Presence or history of panel-reactive anti-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
  • Presence or history of active infection, including hepatitis B, hepatitis C, HIV, or tuberculosis.
  • Negative for Epstein-Barr virus by 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 INR greater than 1.5

  • Severe coexisting cardiac disease, characterized by any one of the following conditions:

    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 the time of 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 (treated or untreated) 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
  • Use of any study medications 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.

Plan studiów

Ta sekcja zawiera szczegółowe informacje na temat planu badania, w tym sposób zaprojektowania badania i jego pomiary.

Jak projektuje się badanie?

Szczegóły projektu

  • Główny cel: Leczenie
  • Przydział: Nie dotyczy
  • Model interwencyjny: Zadanie dla jednej grupy
  • Maskowanie: Brak (otwarta etykieta)

Broń i interwencje

Grupa uczestników / Arm
Interwencja / Leczenie
Eksperymentalny: Islet Transplantation
Participants will receive up to three separate islet transplants and a regimen of immunosuppressive medications consisting of antithymocyte globulin (ATG), sirolimus, and low-dose tacrolimus.
Biologiczny: Allogeneic Pancreatic Islet Cells
200 ml suspension of allogenic human purified islets
Biologiczny: Antithymocyte Globulin
Participants will begin receiving ATG 2 days prior to the first islet transplant. ATG will continue to be given until Day 2 post-transplant.
Lek: Sirolimus
Participants will begin receiving sirolimus 2 days prior to the first islet transplant and will be given for the duration of the study.
Inne nazwy:
  • Rapamycyna
Lek: Tacrolimus
On Day 1 post-transplant, participants will receive tacrolimus, which will also be taken for the duration of the study.
Inne nazwy:
  • Fujimycyna
  • FK-506
Biologiczny: Etanercept
Etanercept will be taken on the day of transplant and Days 3, 7, and 10 post-transplant.
Procedura: Islet Transplantation
Transplantation of pancreatic islet cell
Biologiczny: Basiliximab
Basiliximab will be used in place of ATG for the second and third transplants, if they are necessary.
Inne nazwy:
  • chimeryczne mysie-ludzkie antyCD25
  • Ig gamma-1 chain C region

Co mierzy badanie?

Podstawowe miary wyniku

Miara wyniku
Opis środka
Ramy czasowe
Proportion of participants with a HbA1c less than 7.0% AND free of severe hypoglycemic events
Ramy czasowe: From Day 28 to Day 365 (inclusive) following the first islet transplant, with the day of transplant designated Day 0
The proportion of participants with HbA1c ≤7.0% AND free of severe hypoglycemic events from Day 28 to Day 365 inclusive, following the first islet transplant, with the day of transplant designated Day 0.
From Day 28 to Day 365 (inclusive) following the first islet transplant, with the day of transplant designated Day 0

Miary wyników drugorzędnych

Miara wyniku
Opis środka
Ramy czasowe
Incidence and severity of adverse events related to the islet transplant procedure
Ramy czasowe: 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
Ramy czasowe: 365 days following the first islet transplant
365 days following the first islet transplant
Percent reduction in insulin requirements
Ramy czasowe: 75 days following the first and subsequent islet transplant
75 days following the first and subsequent islet transplant
HbA1c on Day 75 Status Post the First and Subsequent Islet Transplant
Ramy czasowe: 75 days following the first and subsequent islet transplant
The target level for HbA1c for this study is 7.0%. This value is the level recommended by the American Diabetes Association and is considered to be the clinically relevant goal for subjects with Type 1 diabetes (T1D). A HbA1c level of 6.5% is the goal recommended by the American College of Endocrinology.
75 days following the first and subsequent islet transplant
Mean amplitude of glycemic excursions (MAGE)
Ramy czasowe: 75 days following the first and subsequent islet transplant
A MAGE >11.1 mmol/L (200 mg/dL) is indicative of marked glycemic lability.
75 days following the first and subsequent islet transplant
Glycemic liability index (LI)
Ramy czasowe: 75 days following the first and subsequent islet transplant
75 days following the first and subsequent islet transplant
Ryan hypoglycemia severity score (HYPO)
Ramy czasowe: 75 days following the first and subsequent islet transplant
75 days following the first and subsequent islet transplant
Basal (fasting) and 90-minute glucose and C-peptide derived from mixed meal tolerance test (MMTT)
Ramy czasowe: 75 days following the first and subsequent islet transplant
75 days following the first and subsequent islet transplant
β-score on Day 75 Status Post the First and Subsequent Islet Transplant
Ramy czasowe: 75 days following the first and subsequent islet transplant
Beta-score: an assessment of beta-cell function after islet transplantation.
75 days following the first and subsequent islet transplant
C-peptide:glucose creatinine ratio
Ramy czasowe: 75 days following the first and subsequent islet transplant
75 days following the first and subsequent islet transplant
Acute insulin response to glucose, insulin sensitivity, and disposition index derived from the insulin-modified frequently sampled intravenous glucose tolerance (FSIGT) test
Ramy czasowe: 75 days following the first and subsequent islet transplant
75 days following the first and subsequent islet transplant
Glucose variability and hypoglycemia duration derived from the continuous glucose monitoring system (CGMS)
Ramy czasowe: 75 days following the first and subsequent islet transplant
75 days following the first and subsequent islet transplant
Assessment of Quality of Life Using the Short Form 36 Health Survey: Day 75 Status Post First and Final Islet Transplant
Ramy czasowe: 75 days following the first and subsequent islet transplant
The Short-Form 36 Health Survey (SF-36®) is comprised of 36 items and 2 component scores, the Physical Component Score and the Mental Component Score. Each component is transformed into a 0-100 scale (higher numbers indicate greater quality of life) and normalized to have a mean of 50 and standard deviation of 10 for the 1998 general US population. SF-36 results unit of measure: Units on a Scale.
75 days following the first and subsequent islet transplant
Proportion of insulin-independent Participants on Day 365 Status Post the First and Final Islet Transplant
Ramy czasowe: 365 days following the first and final islet transplant
365 days following the first and final islet transplant
Percent reduction in insulin requirements
Ramy czasowe: 365 days following the first and final islet transplant
365 days following the first and final islet transplant
HbA1c on Day 365 Status Post the First and Final Islet Transplant
Ramy czasowe: 365 days following the first and final islet transplant
The target level for HbA1c for this study is 7.0%. This value is the level recommended by the American Diabetes Association and is considered to be the clinically relevant goal for subjects with Type 1 diabetes (T1D). A HbA1c level of 6.5% is the goal recommended by the American College of Endocrinology.
365 days following the first and final islet transplant
MAGE
Ramy czasowe: 365 days following the first and final islet transplant
A MAGE >11.1 mmol/L (200 mg/dL) is indicative of marked glycemic lability.
365 days following the first and final islet transplant
Glycemic liability index (LI): Day 365 Status Post First and Final Islet Transplant
Ramy czasowe: 365 days following the first and final islet transplant
365 days following the first and final islet transplant
Clarke score
Ramy czasowe: 365 days following the first and final islet transplant
The Clarke survey provides a composite indices of hypoglycemia frequency, severity, and symptom recognition.
365 days following the first and final islet transplant
HYPO score
Ramy czasowe: 365 days following the first and final islet transplant
The HYPO(glycemia) score provides a composite indices of hypoglycemia frequency, severity, and symptom recognition.
365 days following the first and final islet transplant
Basal (fasting) and 90-minute glucose and C-peptide (MTT)
Ramy czasowe: 365 days following the first and final islet transplant
365 days following the first and final islet transplant
β-score on Day 365 Status Post First and Final Islet Transplant
Ramy czasowe: 365 days following the first and final islet transplant
Beta-score: an assessment of beta-cell function after islet transplantation.
365 days following the first and final islet transplant
C-peptide: glucose creatinine ratio
Ramy czasowe: 365 days following the first and final islet transplant
365 days following the first and final islet transplant
Assessment of Quality of Life Using the Short Form 36 Health Survey: Day 365 Status Post First and Final Islet Transplant
Ramy czasowe: 365 days following the first and final islet transplant
The Short-Form 36 Health Survey (SF-36®) is comprised of 36 items and 2 component scores, the Physical Component Score and the Mental Component Score. Each component is transformed into a 0-100 scale (higher numbers indicate greater quality of life) and normalized to have a mean of 50 and standard deviation of 10 for the 1998 general US population. SF-36 results unit of measure: Units on a Scale.
365 days following the first and final islet transplant
Proportion of participants receiving a second islet transplant
Ramy czasowe: 365 days following the first and final islet transplant
365 days following the first and final islet transplant
Proportion of participants receiving a third islet transplant
Ramy czasowe: 365 days following the first and final islet transplant
365 days following the first and final islet transplant
Incidence and severity of adverse events related to the immunosuppression therapy
Ramy czasowe: 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 a change in the immunosuppression drug regimen
Ramy czasowe: 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 detecting anti-HLA antibodies not present prior to transplantation
Ramy czasowe: 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
Proportion of insulin-independent participants on Day 75 Status Post First and Subsequent Islet Transplant
Ramy czasowe: 75 days following first and subsequent islet transplant
75 days following first and subsequent islet transplant
Acute insulin response to glucose insulin sensitivity, and disposition index derived from the FSIGT test
Ramy czasowe: 365 days following the first and final islet transplant
Frequently Sampled Intravenous Glucose Tolerance (FSIGT), a measure of insulin-independence, a clinically relevant measure of islet graft function.
365 days following the first and final islet transplant

Współpracownicy i badacze

Tutaj znajdziesz osoby i organizacje zaangażowane w to badanie.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Współpracownicy

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Śledczy

  • Krzesło do nauki: Bernhard Hering, MD, University of Minnesota
  • Krzesło do nauki: Olle Korsgren, PhD, Uppsala University Hospital
  • Krzesło do nauki: Ali Naji, PhD, University of Pennsylvania
  • Krzesło do nauki: Camillo Ricordi, MD, University of Miami
  • Krzesło do nauki: James Shapiro, MD, PhD, University of Alberta
  • Krzesło do nauki: Andrew Posselt, MD, PhD, University of California, San Francisco
  • Krzesło do nauki: Nicole Turgeon, MD, Emory University
  • Krzesło do nauki: Xunrong Luo, MD, PhD, Northwestern Univerity

Publikacje i pomocne linki

Osoba odpowiedzialna za wprowadzenie informacji o badaniu dobrowolnie udostępnia te publikacje. Mogą one dotyczyć wszystkiego, co jest związane z badaniem.

Publikacje ogólne

Przydatne linki

Daty zapisu na studia

Daty te śledzą postęp w przesyłaniu rekordów badań i podsumowań wyników do ClinicalTrials.gov. Zapisy badań i zgłoszone wyniki są przeglądane przez National Library of Medicine (NLM), aby upewnić się, że spełniają określone standardy kontroli jakości, zanim zostaną opublikowane na publicznej stronie internetowej.

Główne daty studiów

Rozpoczęcie studiów

1 października 2006

Zakończenie podstawowe (Rzeczywisty)

1 września 2012

Ukończenie studiów (Rzeczywisty)

1 maja 2014

Daty rejestracji na studia

Pierwszy przesłany

9 lutego 2007

Pierwszy przesłany, który spełnia kryteria kontroli jakości

9 lutego 2007

Pierwszy wysłany (Oszacować)

13 lutego 2007

Aktualizacje rekordów badań

Ostatnia wysłana aktualizacja (Rzeczywisty)

17 lipca 2019

Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości

11 lipca 2019

Ostatnia weryfikacja

1 lipca 2019

Więcej informacji

Terminy związane z tym badaniem

Słowa kluczowe

Dodatkowe istotne warunki MeSH

Inne numery identyfikacyjne badania

  • DAIT CIT-07

Plan dla danych uczestnika indywidualnego (IPD)

Planujesz udostępniać dane poszczególnych uczestników (IPD)?

TAK

Opis planu IPD

Participant level data access and additional relevant materials are available to researchers and the public at: https://www.immport.org/home.

The study Identifier in ImmPort is SDY1178.

Ramy czasowe udostępniania IPD

The data is available. ImmPort is a long-term archive of clinical and mechanistic data.

Kryteria dostępu do udostępniania IPD

Register for ImmPort at: https://www.immport.org/registration and submit a rationale for the purpose of requesting study data access.

ImmPort is a long-term archive of clinical and mechanistic data, a National Institute of Allergy and Infectious Diseases Division of Allergy, Immunology and Transplantation (NIAID DAIT)-funded data repository. This archive is in support of the NIH mission to share data with the public. Data shared through ImmPort is provided by NIH-funded programs, other research organizations and individual scientists, ensuring these discoveries will be the foundation of future research.

Typ informacji pomocniczych dotyczących udostępniania IPD

  • PROTOKÓŁ BADANIA
  • SOK ROŚLINNY
  • ICF
  • ANALITYCZNY_KOD

Badanie danych/dokumentów

  1. Protokół badania
    Identyfikator informacji: SDY1178
    Komentarze do informacji: ImmPort study ID is SDY1178.
  2. Kompletny zestaw opisowych danych i wyników
    Identyfikator informacji: SDY1178
    Komentarze do informacji: ImmPort is a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts. This archive is in support of the NIH mission to share data with the public.

Informacje o lekach i urządzeniach, dokumenty badawcze

Bada produkt leczniczy regulowany przez amerykańską FDA

Tak

Bada produkt urządzenia regulowany przez amerykańską FDA

Nie

Te informacje zostały pobrane bezpośrednio ze strony internetowej clinicaltrials.gov bez żadnych zmian. Jeśli chcesz zmienić, usunąć lub zaktualizować dane swojego badania, skontaktuj się z register@clinicaltrials.gov. Gdy tylko zmiana zostanie wprowadzona na stronie clinicaltrials.gov, zostanie ona automatycznie zaktualizowana również na naszej stronie internetowej .

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