- ICH GCP
- US Clinical Trials Registry
- Klinisk utprøving NCT00446264
Islet Allotransplantation With Steroid Free Immunosuppression
Sequential Islet Transplantation With Steroid Free Immunosuppression for Type 1 Diabetes
The restoration of endogenous insulin secretion carries significant hopes for shifting the paradigm of life long exogenous insulin therapy in selected groups of patients with type 1 diabetes(T1D). After decades of frustrating clinical attempts, the Edmonton group set up in 2000 new standards for islet transplantation in patients with brittle T1D by achieving insulin independence in 80 percent of patients. These seminal results have however proved much more difficult to duplicate than initially expected.
This single center phase 2 clinical trial, duplicating the Edmonton protocol, is designed for confirming the consistent short term efficacy and safety of sequential islet allotransplantation with steroid free immunosuppression in patients with severe T1D.
Studieoversikt
Status
Intervensjon / Behandling
Detaljert beskrivelse
The short term effectiveness of islet transplantation for alleviating hypoglycemia and controlling glucose homeostasis while limiting or even avoiding the nedd for exogenous insulin has been established despite protocol modifications in donor selection, islet preparation or recipient treatment, insulin independence with adequate metabolic control was however rarely prolonged beyond two years. The most frequently proposed explanations include chronic allogenic rejection, recurrence of autoimmunity and beta cell toxicity from administered immunosuppressive drugs.
Fourteen patients were enrolled in this single center phase 2 trial initiated in 2003. Eligible patients were males or females between 18 and 65 years of age, with type 1 diabeted documented for more than 5 years, arginine stimulated C-peptide lower than 0.2ng/ml, and hypoglycemia awareness or documented metabolic lability. Exclusion criteria included body mass index greater than 28Kg/m2, unstable arteriopathy or heart disease, active infection, previous transplantation, insulin daily requirements above 1.2 UI/kg, creatinin clearance below 60 ml/mn/m2 or urinary albumin excretion above 300 mg/day, malignancy, smoking, desire for pregnancy, psychiatric disorders and lack of compliance. The study primary efficacy endpoint was graft survival defined as insulin independence and HbA1c<6.5%. Secondary outcomes were graft function and metabolic control.
Studietype
Registrering (Faktiske)
Fase
- Fase 2
Kontakter og plasseringer
Studiesteder
-
-
-
Lille, Frankrike, 59037
- University Hospital of Lille
-
-
Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
Inclusion Criteria:
- type 1 diabetes documented for more than 5 years
- arginine stimulated C-peptide lower than 0.2 ng/mL
- one of the following:hypoglycemia unawareness OR metabolic lability documented by one or more severe hypoglycemias or two or more hospital admissions for ketoacidosis within the previous year.
Exclusion Criteria:
- body mass index greater than 28 kg/m2
- non stable arteriopathy or heart disease
- active infection
- previous transplantation
- hyperimmunization
- insulin daily needs above 1.2 U/Kg
- creatinine clearance below 60 ml/mn or urinary albumin excretion above 300 mg/d
- malignancy
- smoking
- desire for pregnancy
- psychiatric disorders
- lack of compliance
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: N/A
- Intervensjonsmodell: Enkeltgruppeoppdrag
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
---|---|
Eksperimentell: islet transplantation
Each participant received up to three sequential fresh islet infusions within three months.
|
Øytransplantasjon besto av opptil tre sekvensielle ferske øyinfusjoner innen tre måneder.
Tilgang til portalvenen ble oppnådd under generell anestesi ved perkutan kateterisering av en perifer portalgren under ultralydveiledning eller ved kirurgisk kateterisering av en liten mesenterisk vene.
Andre navn:
Immunosuppressive consisted of Tacrolimus, target through level at 3-6 ng/ml, Sirolimus, target through level at 12-15 ng/ml for three months and at 7-10 ng/ml thereafter.
A five-dose induction course of Daclizumab 1mg/Kg was administered biweekly beginning one hour prior to the first infusion
Andre navn:
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
---|---|---|
Composite Criteria: Insulin Independence and Glycosylated Hemoglobin (HbA1c) Under 6.5% at One Year
Tidsramme: 1 year
|
The percentage of insulin independents subjects with an HbA1c less than 6.5% at one year after last transplant
|
1 year
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
---|---|---|
Hypoglycemic Events
Tidsramme: day 0 to day 365
|
Percentage of subjects free of severe hypoglycemic events from day 0 to day 365 with the day of transplant designated day 0
|
day 0 to day 365
|
Plasma C-peptide
Tidsramme: 1 year
|
Level of plasma C-peptide at 1 year after the first transplant
|
1 year
|
HbA1c < 6.5%
Tidsramme: 1 year
|
The percentage of subjects with HbA1c < 6.5% at 1 year after the first transplant
|
1 year
|
Percentage of Time Spent in Hypoglycemia (<0.70 mg/L)
Tidsramme: 1 year
|
percentage of time spent in hypoglycemia derived from CGMS (Continuous Glucose Monitoring System)
|
1 year
|
Number of Adverse Events
Tidsramme: 1 year
|
The number of adverse events related to the procedure and to the immunosuppression
|
1 year
|
Samarbeidspartnere og etterforskere
Sponsor
Samarbeidspartnere
Etterforskere
- Hovedetterforsker: Francois Pattou, MD, University Hospital, Lille
- Hovedetterforsker: Marie-Christine Vantyghem, MD PhD, University Hospital, Lille
- Hovedetterforsker: Julie Kerr-Conte, PhD, Université de Lille 2
Publikasjoner og nyttige lenker
Generelle publikasjoner
- Vantyghem MC, Chetboun M, Gmyr V, Jannin A, Espiard S, Le Mapihan K, Raverdy V, Delalleau N, Machuron F, Hubert T, Frimat M, Van Belle E, Hazzan M, Pigny P, Noel C, Caiazzo R, Kerr-Conte J, Pattou F; Members of the Spanish Back Pain Research Network Task Force for the Improvement of Inter-Disciplinary Management of Spinal Metastasis. Ten-Year Outcome of Islet Alone or Islet After Kidney Transplantation in Type 1 Diabetes: A Prospective Parallel-Arm Cohort Study. Diabetes Care. 2019 Nov;42(11):2042-2049. doi: 10.2337/dc19-0401. Erratum In: Diabetes Care. 2020 May;43(5):1164.
- Benomar K, Chetboun M, Espiard S, Jannin A, Le Mapihan K, Gmyr V, Caiazzo R, Torres F, Raverdy V, Bonner C, D'Herbomez M, Pigny P, Noel C, Kerr-Conte J, Pattou F, Vantyghem MC. Purity of islet preparations and 5-year metabolic outcome of allogenic islet transplantation. Am J Transplant. 2018 Apr;18(4):945-951. doi: 10.1111/ajt.14514. Epub 2017 Nov 11.
- Caiazzo R, Vantyghem MC, Raverdi V, Bonner C, Gmyr V, Defrance F, Leroy C, Sergent G, Hubert T, Ernst O, Noel C, Kerr-Conte J, Pattou F. Impact of Procedure-Related Complications on Long-term Islet Transplantation Outcome. Transplantation. 2015 May;99(5):979-84. doi: 10.1097/TP.0000000000000458.
- Vantyghem MC, Raverdy V, Balavoine AS, Defrance F, Caiazzo R, Arnalsteen L, Gmyr V, Hazzan M, Noel C, Kerr-Conte J, Pattou F. Continuous glucose monitoring after islet transplantation in type 1 diabetes: an excellent graft function (beta-score greater than 7) Is required to abrogate hyperglycemia, whereas a minimal function is necessary to suppress severe hypoglycemia (beta-score greater than 3). J Clin Endocrinol Metab. 2012 Nov;97(11):E2078-83. doi: 10.1210/jc.2012-2115. Epub 2012 Sep 20.
Studierekorddatoer
Studer hoveddatoer
Studiestart
Primær fullføring (Faktiske)
Studiet fullført (Faktiske)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Anslag)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Anslag)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
- Glukosemetabolismeforstyrrelser
- Sykdommer i immunsystemet
- Autoimmune sykdommer
- Sykdommer i det endokrine systemet
- Sukkersyke
- Diabetes mellitus, type 1
- Hypoglykemi
- Metabolske sykdommer
- Fysiologiske effekter av legemidler
- Molekylære mekanismer for farmakologisk virkning
- Anti-infeksjonsmidler
- Enzymhemmere
- Antineoplastiske midler
- Immunsuppressive midler
- Immunologiske faktorer
- Antibakterielle midler
- Antibiotika, antineoplastisk
- Antifungale midler
- Calcineurin-hemmere
- Takrolimus
- Sirolimus
- Daclizumab
Andre studie-ID-numre
- CP 01/48
- PHRC (2001/1939)
- AFSSAPS 030209 (Annen identifikator: AFSSAPS)
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .
Kliniske studier på Metabolske sykdommer
-
Scripps Whittier Diabetes InstituteFullførtCardio-metabolic Care-Team Intervention (CMC-TI)
Kliniske studier på øytransplantasjon
-
Hanita LensesAvsluttet
-
Mayo ClinicPåmelding etter invitasjonLarynx | Larynx sykdom | Laryngektomi | Larynx stenose | Brudd i strupehodetForente stater
-
Alice Højer ChristensenFullført
-
University of SaskatchewanSaskatchewan Health Research Foundation; Saskatchewan Health Authority... og andre samarbeidspartnereFullførtLivskvalitet | Pasientutdanning | NyretransplantasjonCanada
-
Herbert DuPont, MDTilgjengeligTilbakevendende Clostridium Difficile-infeksjon | Multiresistent Klebsiella Pneumoniae Urinveisinfeksjon
-
Merck Sharp & Dohme LLCFullførtHIV-1 infeksjonForente stater, Australia, Canada, Chile, Colombia, Frankrike, Tyskland, Italia, Japan, Korea, Republikken, Peru, Portugal, Puerto Rico, Den russiske føderasjonen, Sør-Afrika, Spania, Ukraina, Storbritannia
-
Changhai HospitalRekrutteringAvansert magekreftKina
-
University of SaskatchewanVancouver Coastal Health; Saskatchewan Health Authority - Regina Area; Southern... og andre samarbeidspartnereRekrutteringMedisinoverholdelse | NyretransplantasjonForente stater, Canada
-
University of California, IrvineHar ikke rekruttert ennå
-
Merck Sharp & Dohme LLCAktiv, ikke rekrutterendeHIV-1 infeksjonForente stater, Australia, Chile, Israel, Japan, Storbritannia