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Clinical Trial of Immunomodulatory Therapy Using Anti-Thymocyte Globulin and Pegfilgrastim for Recently Onset Type 1 Diabetes (CRITICAL)

Immunomodulatory Therapy for Recently Onset Type 1 Diabetes (CRITICAL)

12

In the treatment group and control group, the numbers of male/female were 3/3 and 4/2, age was 35.3 years and 40.5 years, disease duration was 4.2 months and 8.3 months, BMI was 21.4 kg/m2 and 19.0 kg/m2, HbA1c levels were 6.83%, 6.45%, fasting serum C-peptide concentrations were 1.03 ng/mL, 0.77 ng/mL, respectively (all values were expressed as mean).

Total 12 participants were registered in this study. 6 patients were randomized into the treatment group (Tx), and 6 petiants were randomized into the control group (Ctrl). After 1 patients in the Ctrl were rejected to continue the participation 4 weeks after trial initiation, 6 patients in the Tx and 5 patients in the Ctrl completed all the evaluation duing 104 weeks of study period.

No severe adverse evetns related to the trial were reported.

In terms of safey, No grade 4 and 5 adverse events were reported in both treatment group (Tx) and control group (Ctrl). The number of patients with fever, lymphocytopenia, and dermopathy were significantly more in the Tx than those in Ctrl. in terms of efficacy, the number of patients with %decline of C-peptide AUC (CPR-AUC) less than median during 52 weeks of study period were tended to be lower in the treatment group (P=0.067). However, this tendency was disappeared in the analysis using the %decline in 104 weeks. Changes in HbA1c, glycated albumin, and daily insulin doses in 52 weeks and 104 weeks of observation were not significantly different between the two groups. In the analyses of cellular immunity status, the number of effector memory T cells (TEM) were significantly decreased from 2 weeks to 104 weeks after trial initiation in the Tx compared to that in the Ctrl. The percentages of regulatory T cells (Treg) and Treg/TEM ratio was significantly increased after trial initiation up to 104 weeks.

We evaluated the safety and efficacy of immunomodulatory therapy using anti-thymocyte globulin and pegfilgrastim in recently onset type 1 diabetes. In terms of safety, no grade 4 and 5 severe adverse events were observed. In terms of efficacy, although some analyses showed potantial effects for the preservation of endogenous insulin secretion, the results were not significant. In the future, the efficacy of the treatment should be validated in the trial with more ceses.

Dec. 31, 2023

June. 23, 2023

https://doi.org/10.2337/db23-298-OR

No

Not applicable

https://jrct.mhlw.go.jp/latest-detail/jRCTs031180089

CHUJO DAISUKE

Toyama University Hospital

2630, Sugitani, Toyama 930-0194, Japan

dchujo@med.u-toyama.ac.jp

CHUJO DAISUKE

Toyama University Hospital

2630, Sugitani, Toyama 930-0194, Japan

+81-76-434-2281

dchujo@med.u-toyama.ac.jp

Complete

Jan. 07, 2019

Interventional

randomized controlled trial

open(masking not used)

active control

single assignment

treatment purpose

1. Acute-onset type 1 diabetes
2. Within 12 months since diagnosis
3. Fasting serum C-peptide > 0.3 ng/mL

1. Active infection
2. Pregnancy/breast-feeding
3. Past history of malignant tumor
4. Interstitial pneumonia
5. Severe liver or/and kidney dysfunction
6. Past history of ATG administration
7. Under systemic steroid therapy

Both

Type 1 diabetes

We use anti-thymocyte globulin and pegfilgrastim, those were not used as standard therapies for type 1 diabetes, to evaluate the safety and efficacy for the treatment of recently onset type 1 diabetes.

Frequency of adverse events during 52 weeks of the treatment or observation

1) Changes in the AUC of C-peptide level evaluated with mixed-meal tolerance test during 52 weeks of the treatment or observation
2) Changes in the AUC of C-peptide level evaluated with mixed-meal tolerance test during 104 weeks of the treatment or observation
3) Fasting plasma glucose
4) HbA1c
5) Glycated albumin
6) Fasting serum C-peptide
7) C-peptide index
8) Secretory Units of Islets in Transplantation (SUIT)
9) Mean Amplitude of Glycemic Excursions (MAGE)
10) Standard deviation (SD) of glucose levels evaluated with continuous glucose monitoring (CGM)
11) The percentages of glucose levels within normal range in CGM
12) The percentages of glucose levels above or below normal range in CGM
13) Total daily dose of insulin
14) The frequencies of severe hypoglycemia
15) Islet-related autoantibodies
16) T cell subsets measured by flow cytometry

+81-3-3202-7181

Nov. 19, 2018

none