Bet Cell Therapy in Diabetes Type 1

NCT01379729 | Unknown Phase 2 DMC

• 1 other identifier: BK_TX_07
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

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.

Conditions

Type 1 Diabetes

Keywords

Type 1 Diabetes; Transplantation; Beta Cells; Encapsulation

Outcome Measures

Primary Outcomes (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.

  6 months PT.

Secondary Outcomes (3)

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

  60 months

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

  60 months

• Changes from Baseline

  60 months

Study Arms (2)

Group A

ACTIVE COMPARATOR

Patients with loss of long-term function after intraportal implantation

Other: Transplantation of encapsulated beta cells.

Group B

ACTIVE COMPARATOR

Patients that are candidates for islet cell transplantation

Other: Transplantation of encapsulated beta cells.

Interventions

Transplantation of encapsulated beta cells. OTHER

Implantation of a therapeutical dose of encapsulated beta cells.

Also known as: encapsulated beta cells

Group A

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AZ-VUB: lead
• Universitair Ziekenhuis Brussel: collaborator
• Universitaire Ziekenhuizen KU Leuven: collaborator

Study Sites (2)

UZ Brussel

Brussels, 1090, Belgium

RECRUITING

UZ Leuven

Leuven, 3000, Belgium

RECRUITING

Related Publications (6)

• Gillard P, Keymeulen B, Mathieu C. Beta-cell transplantation in type 1 diabetic patients: a work in progress to cure. Verh K Acad Geneeskd Belg. 2010;72(1-2):71-98.

  PMID: 20726441 BACKGROUND

• Hilbrands R, Huurman VA, Gillard P, Velthuis JH, De Waele M, Mathieu C, Kaufman L, Pipeleers-Marichal M, Ling Z, Movahedi B, Jacobs-Tulleneers-Thevissen D, Monbaliu D, Ysebaert D, Gorus FK, Roep BO, Pipeleers DG, Keymeulen B. Differences in baseline lymphocyte counts and autoreactivity are associated with differences in outcome of islet cell transplantation in type 1 diabetic patients. Diabetes. 2009 Oct;58(10):2267-76. doi: 10.2337/db09-0160. Epub 2009 Jul 14.

  PMID: 19602536 BACKGROUND

• Gillard P, Vandemeulebroucke E, Keymeulen B, Pirenne J, Maes B, De Pauw P, Vanrenterghem Y, Pipeleers D, Mathieu C. Functional beta-cell mass and insulin sensitivity is decreased in insulin-independent pancreas-kidney recipients. Transplantation. 2009 Feb 15;87(3):402-7. doi: 10.1097/TP.0b013e3181928a1c.

  PMID: 19202446 BACKGROUND

• Pipeleers D, Chintinne M, Denys B, Martens G, Keymeulen B, Gorus F. Restoring a functional beta-cell mass in diabetes. Diabetes Obes Metab. 2008 Nov;10 Suppl 4:54-62. doi: 10.1111/j.1463-1326.2008.00941.x.

  PMID: 18834433 BACKGROUND

• Keymeulen B. Therapies aimed at preservation or restoration of beta cell function in type 1 diabetes. Verh K Acad Geneeskd Belg. 2008;70(2):85-103.

  PMID: 18630722 BACKGROUND

• Jacobs-Tulleneers-Thevissen D, Chintinne M, Ling Z, Gillard P, Schoonjans L, Delvaux G, Strand BL, Gorus F, Keymeulen B, Pipeleers D; Beta Cell Therapy Consortium EU-FP7. Sustained function of alginate-encapsulated human islet cell implants in the peritoneal cavity of mice leading to a pilot study in a type 1 diabetic patient. Diabetologia. 2013 Jul;56(7):1605-14. doi: 10.1007/s00125-013-2906-0. Epub 2013 Apr 26.

  PMID: 23620058 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Bart Keymeulen, MD PhD

  Universitair Ziekenhuis Brussel

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bart Keymeulen, MD PhD

CONTACT

+32 2 477 61 11; bart.keymeulen@uzbrussel.be

Robert Hilbrands, MD PhD

CONTACT

+32 2 476 37 34; Robert.Hilbrands@uzbrussel.be

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD. PhD.

Study Record Dates

• First Submitted: May 2, 2011
• First Posted: June 23, 2011
• Study Start: May 1, 2011
• Primary Completion: December 1, 2013
• Study Completion: May 1, 2018
• Last Updated: December 30, 2013

Record last verified: 2013-12

Locations

BE (2)