Bet Cell Therapy in Diabetes Type 1

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by AZ-VUB
Sponsor:
Collaborators:
Universitair Ziekenhuis Brussel
Universitaire Ziekenhuizen Leuven
Information provided by (Responsible Party):
Bart Keymeulen, AZ-VUB
ClinicalTrials.gov Identifier:
NCT01379729
First received: May 2, 2011
Last updated: December 27, 2013
Last verified: December 2013
  Purpose

Primary outcome measurement is a parameter of functional beta cell mass at 6 months PT. Functional beta-cell mass will be calculated using the AUC/min between 150 and 160 min during hyperglycemic clamp at 180 mg/dl.

The investigators hypothesize that functional beta-cell mass will be more than 20% compared to healthy controls.

Secondary outcome measurements:

Functional beta-cell mass at 2,12,18,24,36,48 and 60 months PT.

The investigators will also compare at 2, 6,12, 24,36,48 and 60 months the changes against base-line (base-line = before first intraperitoneal transplantation):

  • metabolic control
  • safety parameters
  • episodes of hypoglycemia
  • islet cell autoantibodies, lymphocyte subsets, T-cell reactivity against auto- and alloantigens using pre-transplant measurements as base-line The investigators hypothesize that metabolic control and prevalence of hypoglycemia, will be significantly improved till PT month 12.

Histopathology of a biopsy specimen of the human intraperitoneal beta cell implant, at time of the second implant. Comparison with composition of graft, identification of microenvironment of host origin and correlation with functional assessment will be performed.


Condition Intervention Phase
Type 1 Diabetes
Other: Transplantation of encapsulated beta cells.
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Functional Survival of Beta Cell Allografts After Transplantation in the Peritoneal Cavity of Non-uremic Type 1 Diabetic Patients

Resource links provided by NLM:


Further study details as provided by AZ-VUB:

Primary Outcome Measures:
  • Primary outcome measurement is a parameter of functional beta cell mass at 6 months PT. Functional beta-cell mass will be calculated using the AUC/min between 150 and 160 min during hyperglycemic clamp at 180 mg/dl. [ Time Frame: 6 months PT. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Functional beta-cell mass at 2,12,18,24,36,48 and 60 months PT. [ Time Frame: 60 months ] [ Designated as safety issue: No ]

    Functional beta-cell mass at 2,12,18,24,36,48 and 60 months PT.

    The investigators will also compare at 2, 6,12, 24,36,48 and 60 months the changes against base-line (base-line = before first intraperitoneal transplantation):

    • metabolic control
    • safety parameters
    • episodes of hypoglycemia
    • islet cell autoantibodies, lymphocyte subsets, T-cell reactivity against auto- and alloantigens using pre-transplant measurements as base-line

  • Functional beta-cell mass at 2,12,18,24,36,48 and 60 months PT. [ Time Frame: 60 months ] [ Designated as safety issue: No ]
    Functional beta-cell mass at 2,12,18,24,36,48 and 60 months PT.

  • Changes from Baseline [ Time Frame: 60 months ] [ Designated as safety issue: Yes ]

    The investigators will also compare at 2, 6,12, 24,36,48 and 60 months the changes against base-line (base-line = before first intraperitoneal transplantation):

    • metabolic control
    • safety parameters
    • episodes of hypoglycemia
    • islet cell autoantibodies, lymphocyte subsets, T-cell reactivity against auto- and alloantigens using pre-transplant measurements as base-line


Estimated Enrollment: 10
Study Start Date: May 2011
Estimated Study Completion Date: May 2018
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Group A
Patients with loss of long-term function after intraportal implantation
Other: Transplantation of encapsulated beta cells.
Implantation of a therapeutical dose of encapsulated beta cells.
Other Name: encapsulated beta cells
Active Comparator: Group B
Patients that are candidates for islet cell transplantation
Other: Transplantation of encapsulated beta cells.
Implantation of a therapeutical dose of encapsulated beta cells.
Other Name: encapsulated beta cells

Detailed Description:

In recipients with loss of long-term function after intraportal implantation (Group A)

  1. To implant an alginate embedded human beta cell graft in a "therapeutic" dose in the intraperitoneal cavity of type 1 diabetic patients under immunosuppression with tacrolimus/MMF.
  2. To obtain histopathology of a biopsy specimen of the intraperitoneal human beta cell implant.
  3. To assess the safety profile, metabolic and immune effects of alginate embedded implants in the intraperitoneal cavity.

    In patients that are candidates for islet cell transplantation (Group B)

  4. To implant an alginate embedded human beta cell graft in a "therapeutic" dose in intraperitoneal cavity of type 1 diabetic patients under immunosuppression with tacrolimus/MMF.
  5. To obtain histopathology of a biopsy specimen of the intraperitoneal human beta cell implant
  6. To assess the safety profile, metabolic and immune effects of alginate embedded implants in the intraperitoneal cavity.
  Eligibility

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

Inclusion Criteria:

Group A:

Patients with loss of long-term function after intraportal implantation (- Patients with type 1 insulin-dependent diabetes who received two intraportal implantations > 12 months ago.

  • Random C-peptide between 0.09 and 0.5 ng/dl (glycemia between 100 and 200 mg/dl)
  • Cooperative and reliable patient giving informed consent by signature

Group B:

Patients that are candidates for islet cell transplantation - age 18-65 years, male or female, Caucasian or not; only subjects < 50 yrs will be allocated to the rituximab treatment arm

  • body weight < 100 kg; patients with a bodyweight of < 80kg, will receive priority
  • patients with a BMI ≤ 27 kg/m2 will receive priority
  • 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:

    • albuminuria 30-1000mg/ 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:

  • Women of reproductive age

    • Smoker
    • EBV antibody negativity
    • HIV 1 & 2 antibody positivity
    • CMV IgM positivity
    • Hepatitis B infection
    • GFR < 45 ml/min/1.72 m2
    • 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 clinical significant HLA antibodies
    • Blood donation within one month prior to screening
    • Symptoms and/or signs of infection, particularly (present or past) endocarditis, osteomyelitis
    • 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
    • Use of illicit drugs or overconsumption of alcohol (> 3 IU/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 a psychiatric disorder that may be exacerbated by the transplantation procedure or interfere with compliance during follow-up
    • Having received antidepressant medications during the last 6 months
    • Participating in another pharmacological study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01379729

Contacts
Contact: Bart Keymeulen, MD PhD +32 2 477 61 11 bart.keymeulen@uzbrussel.be
Contact: Robert Hilbrands, MD PhD +32 2 476 37 34 Robert.Hilbrands@uzbrussel.be

Locations
Belgium
UZ Brussel Recruiting
Brussels, Belgium, 1090
Contact: Bart Keymeulen, MD PhD    +32 2 477 61 11    bart.keymeulen@uzbrussel.be   
Principal Investigator: Bart Keymeulen, MD PhD         
UZ Leuven Recruiting
Leuven, Belgium, 3000
Contact: Pieter , Gillard       pieter.gillard@uzleuven.be   
Contact: Da Hae Lee, MD    +32 16 34 23 98    dahae.lee@uzleuven.be   
Sub-Investigator: Pieter Gillard, MD PhD         
Sponsors and Collaborators
AZ-VUB
Universitair Ziekenhuis Brussel
Universitaire Ziekenhuizen Leuven
Investigators
Principal Investigator: Bart Keymeulen, MD PhD UZ Brussel
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Bart Keymeulen, MD. PhD., AZ-VUB
ClinicalTrials.gov Identifier: NCT01379729     History of Changes
Other Study ID Numbers: BK_TX_07
Study First Received: May 2, 2011
Last Updated: December 27, 2013
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products

Keywords provided by AZ-VUB:
Type 1 Diabetes
Transplantation
Beta Cells
Encapsulation

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Autoimmune Diseases
Endocrine System Diseases
Glucose Metabolism Disorders
Immune System Diseases
Metabolic Diseases

ClinicalTrials.gov processed this record on October 22, 2014