Type 1 DiabetesIMMADIABNCT01747967
Immune Biomarkers of Residual Beta-cell Mass in Type 1 Diabetes
A study testing Meal Test in people with Type 1 Diabetes, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 to 60 years
- Conditions the study is for
- Type 1 Diabetes
- What is being tested?
- Meal Test
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 156 participants
- Where
- 1 siteFrance
- Study dates
- 15 Nov 2011to 30 May 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 60 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
- presence of serum anti-GAD antibodies; and/or
- presence of serum anti-IA-2 antibodies; and/or
Show all 9Show fewer
- for children, presence of serum IAA antibodies; and/or
- presence of T-cell autoimmune responses;
- meal test feasible within 10 weeks of diagnosis.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read more
The main objectives of this study are:
- To evaluate the correlation between beta-cell-reactive T-cell responses and residual insulin secretion.
- To evaluate the correlation between the residual insulin secretion measured by serum C peptide and by urinary C peptide.
- To evaluate the correlation between the residual insulin and glucagon secretion.
Read the detailed 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.
- Conditions
- Type 1 Diabetes
- Being tested
- Meal Test
- Keywords
- Antibodies, Beta cells, C-peptide, GAD, Glucose, Glycemia, Insulin, Meal test, Pancreas, Proinsulin,, T lymphocytes
- Medical subject headings
- Diabetes Mellitus, Type 1, Insulin Resistance, Diabetes Mellitus, Insulin-Dependent, 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Meal TestOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: Meal Test |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: up to 30 months
Secondary outcomes (4)
Correlation between residual insulin secretion estimated by serum and urine C-peptide measurement.
To evaluate the correlation between residual insulin secretion estimated by serum and urine C-peptide measurement.
Measured: at Day 1 and at 18 months
Correlation between residual insulin and glucagon secretion.
To evaluate the correlation between residual insulin and glucagon secretion.
Measured: at Day 1 and at 18 months
Correlation between residual insulin secretion estimated by serum and urine C-peptide measurement.
To evaluate the correlation between residual insulin secretion estimated by serum and urine C-peptide measurement.
Measured: at Day 1 and at 30 months
Correlation between residual insulin and glucagon secretion.
To evaluate the correlation between residual insulin and glucagon secretion.
Measured: at Day 1 and at 30 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2012 (estimated)
- Study start15 Nov 2011
- Primary completion30 May 2017
- Study completion30 May 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Type 1 DiabetesStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 156 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- Institut National de la Santé Et de la Recherche Médicale, France, URC-CIC Paris Descartes Necker Cochin
- Responsible party
- Sponsor
- Investigators
- Etienne LARGER, MD, PhD, Study director, Service de Diabétologie, Hôtel Dieu, AP-HP, ParisRoberto MALLONE, MD, PhD, Principal investigator, INSERM , AP-HP
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01747967
- Sponsor's protocol ID
- K 091101
- Acronym
- IMMADIAB
- Status last verified
- Oct 2025
- First submitted
- 10 Dec 2012
- Last updated
- 20 Nov 2025
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 22997432Culina 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.
PubMed 22858113Scotto 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.
PubMed 22526607Martinuzzi 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.
PubMed 21715316Brezar 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.
PubMed 21700723
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immune Biomarkers of Residual Beta-cell Mass in Type 1 Diabetes
- ClinicalTrials.gov ID
- NCT01747967
- Acronym / sponsor ID
- IMMADIAB / K 091101
- Conditions
- Type 1 Diabetes
- Keywords
- Antibodies, Beta cells, C-peptide, GAD, Glucose, Glycemia, Insulin, Meal test
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 156 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- Institut National de la Santé Et de la Recherche Médicale, France, URC-CIC Paris Descartes Necker Cochin
- Study start
- 15 Nov 2011 (actual)
- Primary completion
- 30 May 2017 (actual)
- Study completion
- 30 May 2017 (actual)
- First posted
- 12 Dec 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- To evaluate the correlation between beta-cell-reactive T-cell responses and residual insulin secretion.
- To evaluate the correlation between the residual insulin secretion measured by serum C peptide and by urinary C peptide.
- To evaluate the correlation between the residual insulin and glucagon secretion.
Detailed 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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Meal test | Experimental | Other: Meal TestBoth 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. |
Who may qualify
- Ages
- 6 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (6 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Meal TestInsulin 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. | Other | Meal test |
Primary outcome
Correlation between residual insulin secretion and T-cell responses against beta-cell antigens.
Time frame: up to 18 months
To evaluate the correlation between residual insulin secretion and T-cell responses against beta-cell antigens.
Correlation between residual insulin secretion and T-cell responses against beta-cell antigens.
Time frame: up to 30 months
To evaluate the correlation between residual insulin secretion and T-cell responses against beta-cell antigens.
4 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2025.
- Background: PubMed 22997432Scotto 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.
- Background: PubMed 22858113Culina 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.
- Background: PubMed 22526607Scotto 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.
- Background: PubMed 21715316Martinuzzi 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.
- Background: PubMed 21700723Brezar 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.
- DeAR Lab Avenir HomepageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Etienne LARGER, MD, PhD study director
Service de Diabétologie, Hôtel Dieu, AP-HP, Paris
Roberto MALLONE, MD, PhD principal investigator
INSERM , AP-HP
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Meal Test in people with Type 1 Diabetes, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Correlation between residual insulin secretion and T-cell responses against beta-cell antigens. (time frame: up to 18 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01747967, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Nov 2025.