Overview

This trial is active, not recruiting.

Condition type 1 diabetes
Treatment meal test
Sponsor Assistance Publique - Hôpitaux de Paris
Start date November 2011
End date March 2017
Trial size 156 participants
Trial identifier NCT01747967, K 091101

Summary

There is currently no imaging technique allowing to directly visualize and measure pancreatic beta-cell mass. Consequently, the best parameter to estimate this mass is the insulin (and its C-peptide byproduct) that residual beta cells are able to produce. This insulin secretion is measured during a meal test, before and at different times after drinking a standardized quantity of nutrients. However, this test is cumbersome (lasting 3 h, with blood samples taken every 30 minutes) and it holds poor sensitivity, probably insufficient to detect very few residual beta cells. Nevertheless, these few residual cells can improve glycemic control and can be instrumental for the clinical efficacy of immune and/or regenerative therapies.

We hypothesize that residual beta cells may not only represent the remaining insulin secretory capacity, but also the antigenic load capable of stimulating beta-cell-reactive T lymphocytes. The disappearance of these T lymphocytes from circulating blood over time may thus be correlated with beta-cell loss. Measuring beta-cell-reactive T-cell responses may therefore provide simple and sensitive immune surrogate markers of residual insulin secretion. Other surrogate markers may be obtained by measuring urinary C peptide or residual secretion of the counter-regulatory hormone glucagon.

The main objectives of this study are:

1. To evaluate the correlation between beta-cell-reactive T-cell responses and residual insulin secretion.

2. To evaluate the correlation between the residual insulin secretion measured by serum C peptide and by urinary C peptide.

3. To evaluate the correlation between the residual insulin and glucagon secretion.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Intervention model single group assignment
Masking open label
Primary purpose diagnostic
Arm
(Experimental)
Both new-onset T1D children and adults will be recruited and followed up through 4 meal tests at 0, 6, 12 , 18, 24 and 30 months.
meal test
Insulin secretion is stimulated by a standardized meal test. Blood and urine samples are collected in order to measure serum and urinary C peptide, glucagon and T-lymphocyte responses against selected beta-cell antigens. The meal test is performed at 0, 6, 12, 18, 24 and 30 months.

Primary Outcomes

Measure
Correlation between residual insulin secretion and T-cell responses against beta-cell antigens.
time frame: up to 18 months
Correlation between residual insulin secretion and T-cell responses against beta-cell antigens.
time frame: up to 30 months

Secondary Outcomes

Measure
Correlation between residual insulin secretion estimated by serum and urine C-peptide measurement.
time frame: at Day 1 and at 18 months
Correlation between residual insulin and glucagon secretion.
time frame: at Day 1 and at 18 months
Correlation between residual insulin secretion estimated by serum and urine C-peptide measurement.
time frame: at Day 1 and at 30 months
Correlation between residual insulin and glucagon secretion.
time frame: at Day 1 and at 30 months

Eligibility Criteria

Male or female participants from 6 years up to 60 years old.

Inclusion Criteria: Pre-inclusion criteria : - children 6-18 years old; - adults 19-60 years old; - patients with a likely diagnosis of T1D, defined by an hyperglycaemia with ketonuria and/or weight loss ≥5% in the last 6 months, requiring insulin therapy. Inclusion criteria: - presence of serum anti-GAD antibodies; and/or - presence of serum anti-IA-2 antibodies; and/or - for children, presence of serum IAA antibodies; and/or - presence of T-cell autoimmune responses; - meal test feasible within 10 weeks of diagnosis. Exclusion Criteria: - recipients of solid organ or hematopoietic tissue transplantations ; - immunosuppressive therapies (anti-histamine agents are not included); - thyroid disease treated by methimazole; - known HIV, HBV or HCV infection; - known progressive cancer disease; - known primary immune deficiency

Additional Information

Official title Immune Biomarkers of Residual Beta-cell Mass in Type 1 Diabetes
Description Type 1 Diabetes (T1D) displays an average 4% annual increase in incidence in most Western countries, particularly in children and young adults. As it requires life-long treatments and it carries significant risks of hypoglycemic and long-term micro- and macrovascular complications, it is a leading cause of disability and public health expenditure. T1D is an autoimmune disease which comprises humoral responses (antibody-producing B lymphocytes) and cellular responses (T lymphocytes). However, antibodies are merely disease markers and do not play any major pathogenic role. Rather, T1D is caused by an abnormal recognition of beta-cell epitopes by T lymphocytes. This recognition leads to destruction of pancreatic insulin-secreting beta cells, hence the need for lifelong insulin treatment. However, beta-cell destruction is rarely complete at the time of T1D onset. The hypothesis under testing is that the residual beta-cell mass may represent not only the endogenous insulin secretory capacity, but also the antigenic load capable of maintaining activation of autoreactive T lymphocytes. In other words, the disappearance of beta-cell-reactive T-cell responses over time may be correlated with beta-cell loss. Measurement of these T-cell responses may thus provide surrogate immune markers of residual beta cells. The primary objective is to evaluate the correlation between residual insulin secretion and T-cell responses directed against beta-cell antigens. The secondary objectives are to evaluate the correlation between residual insulin secretion estimated by serum and urine C-peptide measurement; and to evaluate the correlation between residual insulin and glucagon secretion. The ImMaDiab study is a cohort-based investigation with blood sample collection. Both new-onset T1D children and adults will be recruited. Insulin secretion will be stimulated by a standardized meal test. Following T1D diagnosis, blood and urine samples will be collected every 6 months during 30 months in order to measure serum and urine C peptide, glucagon and T-lymphocyte responses against selected beta-cell antigens.
Trial information was received from ClinicalTrials.gov and was last updated in July 2016.
Information provided to ClinicalTrials.gov by Assistance Publique - Hôpitaux de Paris.