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Bet Cell Therapy in Diabetes Type 1

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ClinicalTrials.gov Identifier: NCT01379729
Recruitment Status : Recruiting
First Posted : June 23, 2011
Last Update Posted : December 30, 2013
Sponsor:
Collaborators:
Information provided by (Responsible Party):

Study Description
Brief Summary:

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 or disease Intervention/treatment Phase
Type 1 Diabetes Other: Transplantation of encapsulated beta cells. Phase 2

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.

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Study Start Date : May 2011
Estimated Primary Completion Date : December 2013
Estimated Study Completion Date : May 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diabetes Type 1
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
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


Outcome Measures

Primary Outcome Measures :
  1. 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. ]

Secondary Outcome Measures :
  1. Functional beta-cell mass at 2,12,18,24,36,48 and 60 months PT. [ Time Frame: 60 months ]

    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

  2. Functional beta-cell mass at 2,12,18,24,36,48 and 60 months PT. [ Time Frame: 60 months ]
    Functional beta-cell mass at 2,12,18,24,36,48 and 60 months PT.

  3. Changes from Baseline [ Time Frame: 60 months ]

    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


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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 Universitair Ziekenhuis Brussel
More Information

Publications:
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
First Posted: June 23, 2011    Key Record Dates
Last Update Posted: December 30, 2013
Last Verified: December 2013

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

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