Long-Term Function of Beta Cell Allografts in Non-Uremic Type 1 Diabetic Patients - Full Text View

Sponsored by:	AZ-VUB
Information provided by:	AZ-VUB
ClinicalTrials.gov Identifier:	NCT00798785

Purpose

The investigators hypothesize that in transplants (month 6 and 12 PT) and in both groups (month 18 till 36 PT), beta cell graft function will be inferior to endogenous beta cell function in normal controls. The investigators hypothesize that in transplants (month 6 and 12) and in both groups (month 18 till 36), insulin resistance will be higher than in normal controls.

Condition	Intervention	Phase
Diabetes Mellitus, Type 1	Drug: prograft	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study
Official Title:	Long-Term Function of Beta Cell Allografts in Non-Uremic Type 1 Diabetic Patients

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Diabetes Type 1

Drug Information available for: Tacrolimus anhydrous Tacrolimus

U.S. FDA Resources

Further study details as provided by AZ-VUB:

Primary Outcome Measures:

Evidence of clinically relevant beta cell graft function [ Time Frame: up to 60 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	40
Study Start Date:	October 2006
Estimated Study Completion Date:	October 2011
Estimated Primary Completion Date:	October 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
group A: Experimental tacrolimus trough levels 6-8 ng/ml	Drug: prograft tacrolimus levels for 3 years between 6 and 8 ng/ml
group B: Experimental tacrolimus level trough: < 1 year 6-8 ng/ml 1-2 years 4-6 ng/ml 2-3 years 2-4 ng/ml	Drug: prograft tacrolimus levels: < 1 year 8-6 ng/ml6-8 1-2 years 4-6 ng/ml 2-3 years 2-4 ng/ml

Detailed Description:

The present proof of concept study addresses the following specific aims:

To monitor over five years the beta cell secretory capacity and the insulin sensitivity in intraportal graft recipients and compare the data with those in age-matched normal controls.
To correlate these data with the degree of metabolic control, the prevalence of hypoglycemia and chronic complications.
To assess the influence of down-tapering the tacrolimus dose during posttransplant years 2-5 on these data, on metabolic control, on the prevalence of hypoglycemia and on safety parameters.
To assess whether changes in beta cell secretory capacity and/or maintenance immune suppression are correlated with changes in immune status as measured by assays of islet cell autoantibodies, lymphocyte subsets and T-cell reactivity against auto- and alloantigens

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age 18-65 years, male or female, caucasian or not
Body weight < 80 kg
BMI ≤ 27 kg/m2
Type 1 insulin-dependent diabetes
C-peptide < 0.07 nmol/l (<0.2 µg/l) 6 min. after glucagon IV (1mg) (glycemia > 180 mg/dl)
Intensive insulin therapy for more than two years, patients with insulin pump during at least 2 months before inclusion will receive priority
Patients should have at least one of the following chronic complications of diabetes:
- Plasma creatinine <2 mg/dl and albuminuria 30-1000 mg/ 24hrs on 3 separate determinations (>1 month) outside an episode of illness, despite intake of ACE inhibitors; mean systolic blood pressure should be under 130 mmHg and mean diastolic blood pressure under 85 mmHg, when measured at home with ambulatory BP monitoring
- Moderate or severe non-proliferative or proliferative retinopathy
- Hypoglycemic unawareness
Cooperative and reliable patient giving informed consent by signature

Exclusion Criteria:

Smoker
EBV antibody negativity
HIV 1 & 2 antibody positivity
CMV IgM positivity
Plasma creatinine ≥ 2 mg/dl and/or albuminuria ≥1000 mg/24 hrs
History of thrombosis or pulmonary embolism
History of malignancy, tuberculosis or chronic viral hepatitis
History of any other serious illness which could be relevant for the protocol
Presence of HLA antibodies
Blood donation within one month prior to screening or during the study
Symptoms and/or signs of infection, particularly (present or past) endocarditis, osteomyelitis, past tuberculosis with requirement for therapy
Any history of hepatic or neoplastic disease
Any history of renal disease (except diabetes)
Abnormal liver function tests and /or NMR of liver
Hemoglobinopathy
History of any illness that, in the opinion of the investigator, might confound the results of the study or pose additional risks to the patient
Pregnancy or use of inadequate contraception by female patients of childbearing potential
Use of illicit drugs or overconsumption of alcohol (> 3 beers/day) or history of drug or alcohol abuse
Being legally incapacitated, having significant emotional problems at the time of the study, or having a history of psychiatric disorders
Having received antidepressant medications during the last 6 months
Having participated the last 12 months or participating in another clinical study

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00798785

Locations

Belgium
University Hospital Brussels
Brussels, Belgium, 1090
University Hospital Leuven
Leuven, Belgium, 3000
Hopital Erasme
Brussel, Belgium
Universitair Ziekenhuis Antwerpen
Antwerpen, Belgium

Sponsors and Collaborators

AZ-VUB

Investigators

Principal Investigator:

Bart Keymeulen, MD PhD

University Hospital Brussel

More Information

Publications:

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. Epub 2006 Nov 7.

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. Epub 2003 Feb 15.

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.

Responsible Party:	University Hospotal Brussels ( Prof. dr. B. Keymeulen )
Study ID Numbers:	BK_TX_06
Study First Received:	November 25, 2008
Last Updated:	November 25, 2008
ClinicalTrials.gov Identifier:	NCT00798785 History of Changes
Health Authority:	Belgium: Federal Agency for Medicinal Products and Health Products

Keywords provided by AZ-VUB:

diabetes mellitus type 1
pancreatic beta cell
transplantation

Study placed in the following topic categories:

Autoimmune Diseases
Metabolic Diseases
Immunologic Factors
Diabetes Mellitus, Type 1
Diabetes Mellitus
Endocrine System Diseases

Diabetes Mellitus Type 1
Tacrolimus
Endocrinopathy
Glucose Metabolism Disorders
Immunosuppressive Agents
Metabolic Disorder

Additional relevant MeSH terms:

Autoimmune Diseases
Metabolic Diseases
Immunologic Factors
Immune System Diseases
Diabetes Mellitus, Type 1
Physiological Effects of Drugs

Diabetes Mellitus
Endocrine System Diseases
Tacrolimus
Glucose Metabolism Disorders
Immunosuppressive Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 10, 2009