Diabetes type 1 Nutritional, Metabolic, Endocrine Insulin-dependent diabetes mellitus
Conditions
Interventions
Patients will receive a single or double intravenous infusions of ex vivo expanded autologous CD4+CD25+CD127- T regulatory cells (Tregs) in a total dose of up to 30x106cells/kg b.w. All the patients w
Sponsors
Medical University of Gdansk (Poland)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: TREGS STUDY ARM 1. Male and female patients 5 to 18 years of age. 2. Ability to provide written informed consent by parents (and patients if above 16years old) 3. Clinical history of autoimmune type 1 diabetes diagnosed within recent 2 months and presence of at least one type of anti-islet autoantibody: antiGAD, antiIA2, IAA, ICA (high titer). 4. Fasting plasma C-peptide more than 0.4ng/mL 5. Involvement of the patients and parents in the intensive diabetes management defined as self monitoring of glucose values no less than three times/ day and by the administration of insulin injections each day or insulin pump therapy. 6. Patient and parents mentally stable and able to comply with the procedures of the study protocol. 7. Appropriate venous access for blood drawing. CONTROL GROUP ARM : 1. Patients fulfilling the inclusion criteria from 1 to 6 but 2. EXCLUDED from blood drawing due to inappropriate venous access.
Exclusion criteria
Exclusion criteria: 1. No agreement for participation in the study and no inform consent singed 2. Other than autoimmune type 1 diabetes 3. Age below 5 and above 18 years at the time of recruitment 4. Carriage of HLA-DQB1*0602 allele 5. IgA deficiency or other genetic defect present 6. Body mass index (BMI) outside the range of 25-75 percentiles for a particular age. 7. Presence or history of active infection including hepatitis B, hepatitis C, HIV, syphilis or tuberculosis (TB). Subjects with laboratory evidence of active infection are excluded even in the absence of clinical evidence of active infection. 8. Invasive aspergillus, histoplasmosis, or coccidioidomycosis infection within one year prior to study enrollment. 9. Any history of malignancy 10. Baseline Hb below the lower limits of the reference range ; lymphopenia (300 mg/g creatinine). 17. For female subjects older than 15 years positive pregnancy test, unwillingness to use effective contraceptive measures for the duration of the study and 4 months after discontinuation, when appropriate. For male subjects: intent to procreate during the duration of the study or within 4 months after discontinuation or unwillingness to use effective measures of contraception when appropriate. 18. Excessive anxiety of the patient or parents related to the procedures. 19. Any medical condition that, in the opinion of the investigator, will interfere with safe participation in the trial. 20. For parents and children older than 15 years: known active alcohol or substance abuse.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. The proportion of subjects with no reported adverse effects of the treatment from day 0 to two years after administration of Tregs. The day of Tregs infusion is designated Day 0 (as recommended by the Ethics Committee). 2. The proportion of subjects with daily insulin dose (DDI) = 0.5UI/kg b.w. and plasma fasting C-peptide levels more than 0.5ng/mL present without any stimulation at Day 365. The day of Tregs infusion is designated Day 0. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. The proportion of subjects with daily insulin dose (DDI) = 0.5UI/kg b.w. and plasma fasting C-peptide levels >0.5ng/mL present without any stimulation at 120days after the administration of Tregs. The day of Tregs infusion is designated Day 0. 2. The proportion of subjects with daily insulin dose (DDI) = 0.5UI/kg b.w. and plasma fasting C-peptide levels >0.5ng/mL present without any stimulation from Day 0 to two years after the administration of Tregs. The day of Tregs infusion is designated Day 0. 3. The proportion of subjects with =15% reduction of DDI/kg b.w. from baseline at 120days after the administration of Tregs. The day of Tregs infusion is designated Day 0. 4. The proportion of subjects with =15% reduction of DDI/kg b.w. from baseline at 2 years after the administration of Tregs. The day of Tregs infusion is designated Day 0. 5. The proportion of subjects with =2% reduction of HbA1c from baseline at 120days after the administration of Tregs. The day of Tregs infusion is designated Day 0. 6. The proportion of subjects with HbAlc =6.5% at 120days after the administration of Tregs. The day of Tregs infusion is designated Day 0. 7. The proportion of subjects with HbAlc =7.0% at 120days after the administration of Tregs. The day of Tregs infusion is designated Day 0. 8. The proportion of subjects with HbAlc =6.5% at Day 365. The day of Tregs infusion is designated Day 0. 9. The proportion of subjects with HbAlc =7.0% at Day 365. The day of Tregs infusion is designated Day 0. 10. The proportion of subjects with HbAlc =6.5% from Day 0 to two years after the administration of Tregs. The day of Tregs infusion is designated Day 0. 11. The proportion of subjects with HbAlc =7.0% from Day 0 to two years after the administration of Tregs. The day of Tregs infusion is designated Day 0. | — |
Countries
Poland
Outcome results
None listed