Bet Cell Therapy in Diabetes Type 1

This study is currently recruiting participants.
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

May 2, 2011
December 27, 2013
May 2011
December 2013   (final data collection date for primary outcome measure)
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 ]
Same as current
Complete list of historical versions of study NCT01379729 on ClinicalTrials.gov Archive Site
  • 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
Same as current
Not Provided
Not Provided
 
Bet Cell Therapy in Diabetes Type 1
Functional Survival of Beta Cell Allografts After Transplantation in the Peritoneal Cavity of Non-uremic Type 1 Diabetic Patients

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.

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.
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Type 1 Diabetes
Other: Transplantation of encapsulated beta cells.
Implantation of a therapeutical dose of encapsulated beta cells.
Other Name: encapsulated beta cells
  • Active Comparator: Group A
    Patients with loss of long-term function after intraportal implantation
    Intervention: Other: Transplantation of encapsulated beta cells.
  • Active Comparator: Group B
    Patients that are candidates for islet cell transplantation
    Intervention: Other: Transplantation of encapsulated beta cells.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
10
May 2018
December 2013   (final data collection date for primary outcome measure)

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
Both
18 Years to 65 Years
No
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
Belgium
 
NCT01379729
BK_TX_07
Yes
Bart Keymeulen, AZ-VUB
AZ-VUB
  • Universitair Ziekenhuis Brussel
  • Universitaire Ziekenhuizen Leuven
Principal Investigator: Bart Keymeulen, MD PhD UZ Brussel
AZ-VUB
December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP