Immune Biomarkers of Residual Beta-cell Mass in Type 1 Diabetes

NCT01747967 | Completed

• 1 other identifier: K 091101
• Study Type: interventional
• Target: 156
• Locations: 1 country
• Sites: 1

Brief 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. 1.To evaluate the correlation between beta-cell-reactive T-cell responses and residual insulin secretion.
2. 2.To evaluate the correlation between the residual insulin secretion measured by serum C peptide and by urinary C peptide.
3. 3.To evaluate the correlation between the residual insulin and glucagon secretion.

Conditions

Type 1 Diabetes

Keywords

Antibodies; Beta cells; C-peptide; GAD; Glucose; Glycemia; Insulin; Meal test; Pancreas; Proinsulin,; T lymphocytes

Outcome Measures

Primary Outcomes (2)

• Correlation between residual insulin secretion and T-cell responses against beta-cell antigens.

  To evaluate the correlation between residual insulin secretion and T-cell responses against beta-cell antigens.

  up to 18 months

• Correlation between residual insulin secretion and T-cell responses against beta-cell antigens.

  To evaluate the correlation between residual insulin secretion and T-cell responses against beta-cell antigens.

  up to 30 months

Secondary Outcomes (4)

• Correlation between residual insulin secretion estimated by serum and urine C-peptide measurement.

  at Day 1 and at 18 months

• Correlation between residual insulin and glucagon secretion.

  at Day 1 and at 18 months

• Correlation between residual insulin secretion estimated by serum and urine C-peptide measurement.

  at Day 1 and at 30 months

• Correlation between residual insulin and glucagon secretion.

  at Day 1 and at 30 months

Study Arms (1)

Meal test

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.

Other: Meal Test

Interventions

Meal Test OTHER

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.

Meal test

Eligibility Criteria

• Age: 6 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Institut National de la Santé Et de la Recherche Médicale, France: collaborator
• URC-CIC Paris Descartes Necker Cochin: collaborator

Study Sites (1)

INSERM U1016 - DeAR Lab Avenir, Hôpital Cochin

Paris, 75014, France

Location

Related Publications (5)

• Scotto M, Afonso G, Osterbye T, Larger E, Luce S, Raverdy C, Novelli G, Bruno G, Gonfroy-Leymarie C, Launay O, Lemonnier FA, Buus S, Carel JC, Boitard C, Mallone R. HLA-B7-restricted islet epitopes are differentially recognized in type 1 diabetic children and adults and form weak peptide-HLA complexes. Diabetes. 2012 Oct;61(10):2546-55. doi: 10.2337/db12-0136.

  PMID: 22997432 BACKGROUND

• Culina S, Mallone R. Immune biomarkers in immunotherapeutic trials for type 1 diabetes: cui prodest? Diabetes Metab. 2012 Nov;38(5):379-85. doi: 10.1016/j.diabet.2012.05.005. Epub 2012 Jul 31.

  PMID: 22858113 BACKGROUND

• Scotto M, Afonso G, Larger E, Raverdy C, Lemonnier FA, Carel JC, Dubois-Laforgue D, Baz B, Levy D, Gautier JF, Launay O, Bruno G, Boitard C, Sechi LA, Hutton JC, Davidson HW, Mallone R. Zinc transporter (ZnT)8(186-194) is an immunodominant CD8+ T cell epitope in HLA-A2+ type 1 diabetic patients. Diabetologia. 2012 Jul;55(7):2026-31. doi: 10.1007/s00125-012-2543-z. Epub 2012 Apr 20.

  PMID: 22526607 BACKGROUND

• Martinuzzi E, Afonso G, Gagnerault MC, Naselli G, Mittag D, Combadiere B, Boitard C, Chaput N, Zitvogel L, Harrison LC, Mallone R. acDCs enhance human antigen-specific T-cell responses. Blood. 2011 Aug 25;118(8):2128-37. doi: 10.1182/blood-2010-12-326231. Epub 2011 Jun 28.

  PMID: 21715316 BACKGROUND

• Brezar V, Carel JC, Boitard C, Mallone R. Beyond the hormone: insulin as an autoimmune target in type 1 diabetes. Endocr Rev. 2011 Oct;32(5):623-69. doi: 10.1210/er.2011-0010. Epub 2011 Jun 23.

  PMID: 21700723 BACKGROUND

Related Links

• DeAR Lab Avenir Homepage

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Insulin Resistance; Diabetes Mellitus, Insulin-Dependent, 2

Condition Hierarchy (Ancestors)

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

Study Officials

• Etienne LARGER, MD, PhD

  Service de Diabétologie, Hôtel Dieu, AP-HP, Paris

  STUDY DIRECTOR

• Roberto MALLONE, MD, PhD

  INSERM , AP-HP

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2012
• First Posted: December 12, 2012
• Study Start: November 15, 2011
• Primary Completion: May 30, 2017
• Study Completion: May 30, 2017
• Last Updated: November 20, 2025

Record last verified: 2025-10

Locations

FR (1)