Clinical trial NCT00623610: Beta-Cell Transplantation in Pre-Uremic Patients With Type 1 Diabetes
Official title: Beta-Cell Transplantation in Pre-Uremic Patients With Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Diabetes Mellitus, Type 1
Keywords: Diabetes mellitus, type 1
pancreatic beta cell
transplantation
Lead sponsor: AZ-VUB
Sponsor class: OTHER
Collaborators: name: Vrije Universiteit Brussel
name: Universitaire Ziekenhuizen KU Leuven
name: Universiteit Antwerpen
name: Erasme University Hospital
First posted: 2008-02-26
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To examine whether temporary immunosuppression with ATG, tacrolimus and MMF allows prolonged survival of beta cell allografts in type 1 diabetic patients with early chronic complications of diabetes.


Eligibility criteria: Inclusion Criteria:

* type 1 insulin-dependent diabetic patients in relatively good general condition
* non-smoker
* body weight \< 80 kg
* C-peptide \< 0.03 nmol/l (\<0.09 µg/l) 6 min. after glucagon IV (1mg) (glycemia \> 180 mg/dl)
* EBV antibody positive
* cooperative and reliable patient giving informed consent by signature; the patient should be informed in sufficient detail on the content and procedure of the protocol, indicating potential risks of intervention and of immunosuppressive therapy; the patient should also be informed that withdrawal of immunosuppressive therapy in patients with persistent plasma C-peptide positivity may result in subsequent loss of ß-cell graft function; the ß cell implant should be identified as a clinical trial

Exclusion Criteria:

* history of thrombosis or pulmonary embolism
* abnormal liver function
* HLA antibodies

Primary outcomes:
measure: Evidence of clinically relevant beta cell function.
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Universitair Ziekenhuis and Diabetes Research Center - Brussels Free University-VUB
city: Leuven
country: Belgium
facility: Department of Endocrinology and Nephrology, UZ Gasthuisberg, Katholieke Universiteit Leuven -KUL
Study officials:
affiliation: Universitair Ziekenhuis Brussel
name: Bart Keymeulen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Movahedi B, Keymeulen B, Lauwers MH, Goes E, Cools N, Delvaux G. Laparoscopic approach for human islet transplantation into a defined liver segment in type-1 diabetic patients. Transpl Int. 2003 Mar;16(3):186-90. doi: 10.1007/s00147-002-0517-7. Epub 2003 Feb 15.
citation: Maleux G, Gillard P, Keymeulen B, Pipeleers D, Ling Z, Heye S, Thijs M, Mathieu C, Marchal G. Feasibility, safety, and efficacy of percutaneous transhepatic injection of beta-cell grafts. J Vasc Interv Radiol. 2005 Dec;16(12):1693-7. doi: 10.1097/01.RVI.0000182506.88739.39.
citation: Keymeulen B, Gillard P, Mathieu C, Movahedi B, Maleux G, Delvaux G, Ysebaert D, Roep B, Vandemeulebroucke E, Marichal M, In 't Veld P, Bogdani M, Hendrieckx C, Gorus F, Ling Z, van Rood J, Pipeleers D. Correlation between beta cell mass and glycemic control in type 1 diabetic recipients of islet cell graft. Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17444-9. doi: 10.1073/pnas.0608141103. Epub 2006 Nov 7.
citation: Lee D, Gillard P, Hilbrands R, Ling Z, Van de Velde U, Jacobs-Tulleneers-Thevissen D, Maleux G, Lapauw B, Crenier L, De Block C, Mathieu C, Pipeleers D, Keymeulen B. Use of Culture to Reach Metabolically Adequate Beta-cell Dose by Combining Donor Islet Cell Isolates for Transplantation in Type 1 Diabetes Patients. Transplantation. 2020 Oct;104(10):e295-e302. doi: 10.1097/TP.0000000000003321.
citation: Balke EM, Demeester S, Lee D, Gillard P, Hilbrands R, Van de Velde U, Van der Auwera BJ, Ling Z, Roep BO, Pipeleers DG, Keymeulen B, Gorus FK. SLC30A8 polymorphism and BMI complement HLA-A*24 as risk factors for poor graft function in islet allograft recipients. Diabetologia. 2018 Jul;61(7):1623-1632. doi: 10.1007/s00125-018-4609-z. Epub 2018 Apr 20.
citation: Lee D, Keymeulen B, Hilbrands R, Ling Z, Van de Velde U, Jacobs-Tulleneers-Thevissen D, Maleux G, Lapauw B, Crenier L, De Block C, Mathieu C, Pipeleers D, Gillard P. Age and Early Graft Function Relate With Risk-Benefit Ratio of Allogenic Islet Transplantation Under Antithymocyte Globulin-Mycophenolate Mofetil-Tacrolimus Immune Suppression. Transplantation. 2017 Sep;101(9):2218-2227. doi: 10.1097/TP.0000000000001543.
citation: Ling Z, De Pauw P, Jacobs-Tulleneers-Thevissen D, Mao R, Gillard P, Hampe CS, Martens GA, In't Veld P, Lernmark A, Keymeulen B, Gorus F, Pipeleers D. Plasma GAD65, a Marker for Early beta-Cell Loss After Intraportal Islet Cell Transplantation in Diabetic Patients. J Clin Endocrinol Metab. 2015 Jun;100(6):2314-21. doi: 10.1210/jc.2015-1216. Epub 2015 Mar 27.
citation: Huurman VA, Hilbrands R, Pinkse GG, Gillard P, Duinkerken G, van de Linde P, van der Meer-Prins PM, Versteeg-van der Voort Maarschalk MF, Verbeeck K, Alizadeh BZ, Mathieu C, Gorus FK, Roelen DL, Claas FH, Keymeulen B, Pipeleers DG, Roep BO. Cellular islet autoimmunity associates with clinical outcome of islet cell transplantation. PLoS One. 2008 Jun 18;3(6):e2435. doi: 10.1371/journal.pone.0002435.