Polyclonal Anti-T-Lymphocyte Globulin (ATG) in Type 1 Diabetes

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2004 by Institute for Clinical and Experimental Medicine.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Ministry of Health, Czech Republic
Information provided by:
Institute for Clinical and Experimental Medicine
ClinicalTrials.gov Identifier:
NCT00190502
First received: September 11, 2005
Last updated: January 8, 2007
Last verified: February 2004
  Purpose

The primary objective of the study is:

  • To compare the effect of ATG treatment together with intensified insulin therapy (Group 1) on fasting and glucagon-stimulated C-peptide production with that of intensified insulin therapy only (Group 2) in type 1 diabetes mellitus of recent onset

Secondary objectives are:

  • To compare the insulin doses between the two groups at 6, 12, 18, and 24 months after diabetes onset
  • To compare the course of the specific humoral markers of autoimmunity between the groups
  • To evaluate the significance of in vitro testing of specific T-cell activation by an autoantigen in the long-term follow-up in type 1 diabetes
  • To assess the safety of ATG treatment in type 1 diabetes

Condition Intervention
Diabetes Mellitus, Type 1
Drug: Polyclonal anti-T-cell antibodies

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind
Primary Purpose: Educational/Counseling/Training
Official Title: The Use of Polyclonal Anti-T-Lymphocyte Globulin to Prevent Progression of Autoimmune Beta-Cell Destruction in Recent Type 1 Diabetes

Resource links provided by NLM:


Further study details as provided by Institute for Clinical and Experimental Medicine:

Primary Outcome Measures:
  • C-peptide production

Secondary Outcome Measures:
  • Diabetes remission rate
  • Insulin dose

Estimated Enrollment: 28
Study Start Date: November 2000
Estimated Study Completion Date: December 2007
Detailed Description:

This is a randomized, controlled, single-blind and parallel group study. After admission to the hospital, initial physical and laboratory examinations will be performed. Laboratory tests and medical treatment not related to the experimental protocol (except for immunosuppressive drugs) will be performed as clinically needed. Patients who fulfill the inclusion criteria and give their informed consent to participate in the study will be randomized to be treated either with a course of ATG-Fresenius together with intensified insulin therapy (Group 1) or with intensified insulin therapy only (Group 2).

For the study purpose, clinical and laboratory status of the patients will be assessed at 14 occasions (screening, visit 1 – visit 14). Thereafter, an extended follow-up study is planned with evaluations every 6 months.

Patients will be referred to the research institution by cooperating general practitioners and diabetes specialists, preferably before initiation of insulin therapy. After diabetes confirmation (according to WHO criteria) and initial clinical and biochemical examinations (typical for all patients with recent onset diabetes) the purpose, potential risk and benefits and the design of the study will be explained. Subjects willing to participate in the study will be asked to give their written informed consent.

All patients will be actively educated in diabetes management and intensified insulin therapy (3 – 4 daily injections of human insulin, glucose self-monitoring) will be initiated according to individual needs. In subjects randomized to Group 1, 4 doses of ATG Fresenius (first dose of 9 mg/kg of body weight, then 3 consecutive doses of 3 mg/kg) will be administered intravenously over 4 hours. Subjects in Group 2 will be treated with saline infusion (500 ml) on the same days. 1 hour before the first ATG administration, a cutaneous tolerance test (0.2 ml of the final solution) will be performed. Approximately 10 days after admission the patients will be dismissed. Besides scheduled ambulant visits, all subjects will be followed-up as clinically needed. In Paediatric patients (age 15-18 years), recommendations of a paediatric endocrinologist concerning diabetes management will be respected.

After completion of the study each patient’s diabetes specialist will be acquainted with the course of the treatment so far and the patients will be treated according to individual needs. They will be seen regularly once per year in the Department of Diabetes in IKEM for the next 3 years.

Discontinuation of the study:

Participation in the study may be at all times stopped according to the patient’s will. Should this require the medical status of the patients, the study may be interrupted based on the investigator’s decision during the period of ATG administration.

Study population:

Twenty four patients with type 1 diabetes mellitus of recent onset will be followed in the Institute for Clinical and Experimental Medicine in Prague. Inclusion criteria will be:

  • Type 1 diabetes mellitus of known duration up to 6 weeks
  • Men and women 15 – 35 years old, body mass index up to 32 kg/m2, exclusion of gravidity in women
  • Insulin dose up to 40 IU per day for no longer than 1 month
  • C-peptide level ≥ 0.3 pmol/ml 4 min. following iv. administration of 1 ml glucagon
  • No previous immunosuppressive therapy, no concurrent severe infection, granulocyte count ≥ 2 x 10^9/l, platelet count ≥ 120 x 10^9/l
  Eligibility

Ages Eligible for Study:   15 Years to 35 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Type 1 diabetes
  • Body mass index up to 32 kg/m2
  • Exclusion of gravidity in women
  • Known diagnosis of diabetes of less than 6 weeks
  • Insulin dose of up to 40 IU per day for no longer than 1 month
  • Positive for at least one autoantibody (GAD, IA2, ICA)
  • C-peptide level ≥ 0.3 pmol/ml 4 min. following intravenous (IV) administration of 1 ml glucagon
  • No concurrent severe infection
  • Granulocyte count ≥ 2 x 10^9/l
  • Platelet count ≥ 120 x 10^9/l

Exclusion Criteria:

  • Other non-diabetes related autoimmune disease
  • Previous immunosuppressive therapy
  • Any clinical impairment precluding immunosuppressive therapy
  • Leucopenia or thrombocytopenia
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00190502

Contacts
Contact: Frantisek Saudek, MD. frsa@medicon.cz

Locations
Czech Republic
Institute for Clinical and Experimental Medicine, Department of Diabetes Recruiting
Prague, Czech Republic, 14021
Contact: Frantisek Saudek, MD.       frsa@medicon.cz   
Principal Investigator: Frantisek Saudek, MD         
Sub-Investigator: Petr Boucek, MD.         
Sub-Investigator: Tereza Havrdova         
Sponsors and Collaborators
Institute for Clinical and Experimental Medicine
Ministry of Health, Czech Republic
Investigators
Study Chair: Frantisek Saudek, MD. Institute for Clinical and Experimental Medicine, Prague
  More Information

Publications:
Saudek F., Havrdova T., Boucek P., Karasova L., Novota P., Skibova J.: Polyclonal anti-T-cell therapy for type 1 diabetes mellitus of recent onset. Review of Diabetic Studies 1, 2004: 80-88.

ClinicalTrials.gov Identifier: NCT00190502     History of Changes
Other Study ID Numbers: KD CD IKEM 1, NB/6541-3 IGA MZCR
Study First Received: September 11, 2005
Last Updated: January 8, 2007
Health Authority: Czech Republic: Ministry of Health

Keywords provided by Institute for Clinical and Experimental Medicine:
Type 1 diabetes mellitus
Immune intervention
Polyclonal antibodies
Type 1 diabetes of recent onset
C-peptide level 0.3 pmol/l or higher
Positivity of at least one marker of autoimmunity (diabetes)

Additional relevant MeSH terms:
Diabetes Mellitus, Type 1
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Antibodies
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 22, 2014