Type 1 DiabetesNCT04977635
Biomarkers of Heterogeneity in Type 1 Diabetes
An observational study of Type 1 Diabetes, run by Diabeter Nederland BV at 3 sites in Netherlands.
Trial summary
Biomarkers of heterogeneity in type 1 diabetes: establishment of a biobank and an integrated approach to clinical and metabolic phenotyping of individuals with established T1DM. In this project the investigators are searching for biomarkers in 600 patients with established (>5 years) diabetes. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Type 1 Diabetes
- How many people
- 611 participants
- Where
- 3 sitesNetherlands
- Study dates
- 8 Jun 2016to 31 Dec 2021
- Phase
- Observational
- 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 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patients with >= 5 years duration of type 1 diabetes, age >= 16 years, treated for type 1 diabetes at a diabetes center participating in this study
Who may be able to join
- Type 1 diabetes determined by either autoantibodies or based on clinical and historical data or both
- At least 5 years (1825 days) of type 1 diabetes
- Minimum age 16 years
- Treated for type 1 diabetes at a diabetes center participating in this study
- Subject understands study protocol and agrees to comply with it and has been able to read the patient information sheet, has had time to ask questions and get answers and gives signed informed consent.
Who cannot join
- Non-type 1 diabetes
- Patients with a duration of type 1 diabetes below 5 years
- Patients under the age of 16 years
- Pregnancy and breastfeeding, until 3 months (12 weeks) after childbirth or breastfeeding
- On experimental medication or participating in other studies with conflicting goals and schedules
- Diseases or conditions that the investigator/physician believes to be a contraindication to participate
- Unwilling to be informed on incidental findings.
Trial locations and contacts
3 sites in 1 country.
Netherlands3 sites
University Medical Center Groningen
Groningen, 9700 RB
Martine MC de Vries
Rotterdam, 3011 TA
Haaglanden Medical Center
The Hague, 2512 VA
About this study
Official title: Biomarkers of Heterogeneity in Type 1 Diabetes: an Integrated Approach to Clinical and Metabolic Phenotyping of Individuals With Established Type 1 Diabetes
Biomarkers of heterogeneity in type 1 diabetes: establishment of a biobank and an integrated approach to clinical and metabolic phenotyping of individuals with established T1DM. In this project the investigators are searching for biomarkers in 600 patients with established (>5 years) diabetes. The inter-relation and patterns of expression in clinical, (auto)immune, metabolic, inflammatory and other parameters, and (potential) biomarkers are investogated. Blood and urine samples are collected annually (over 3 years) in standardized conditions and biobanked. In addition, 150 patients will undergo additional metabolic testing (such as mixed meal-tests).
Read the detailed description
Identifying biomarkers of type 1 diabetes heterogeneity can help to stage the disease, and identify risks such as the early development of damage and complications.
Type 1 diabetes has long been considered to be an autoimmune disease in which failure of immune tolerance induces a specific immune attack on insulin-producing beta-cells. Recent research shows that the pathophysiology of type 1 diabetes is heterogeneous, involving various beta-cell-specific processes, different genetic predispositions, and several disease stages. It is very important to recognize this heterogeneity as it results in an accumulation of differences in outcomes during the course of the disease.
This heterogeneity requires further elucidation as a heterogeneous disease is likely to require multiple approaches to stop or cure the pathophysiological pathways. This underscores the need for more biomarkers to identify this heterogeneity, the different phases of disease and the effects of interventions and cures.
In many countries and research groups, data and samples from newly-diagnosed individuals (i.e. within the first 6 months after diagnosis) have been collected and studied. Fewer data and samples are available from patients with longer disease duration. This prompted JDRF to grant a strategic research agreement (SRA) to Diabeter and UMC Groningen. Both clinics have access to a substantial clinical database since 1998 with medical record data of > 3500 type 1 diabetes patients.
In this BIOMARKER project, the investigators intend to analyze hormonal, biochemical, immunological, inflammatory and psychological biomarkers of type 1 diabetes in patients with a disease duration of > 5 years. A sample repository (serum, plasma, urine, DNA, RNA) is established which is also accessible to other interested collaborators.
The collection currently includes:
- Fasting samples (serum, plasma, urine, DNA, RNA) from 600 patients with type 1 diabetes (> 5 years duration) taken annually at 3 timepoints
- Samples from 150 patients who underwent Mixed Meal Tolerance Tests (MMTT with 5 timepoints) at 2 occasions (1-year interval)
- Data from questionnaires on psychosocial burden, quality of life, neuropathy and hypoglycaemia completed by the patients
- Clinical datasets on their health, diabetes history, family history and clinical course during treatment
- Conditions
- Type 1 Diabetes
- Keywords
- Heterogeneity, Biomarkers, C-peptide, Glucagon, Impaired awareness of hypoglycemia, Mixed meal tolerance test, Genetics
- Medical subject headings
- Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 600-cohort | Patients with long-term (> 5 years) type 1 diabetes aged 16 years and older As this is an observational study there is no intervention. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline remaining C-peptide production at 1 year and 2 years as measured by the Beckman ultrasensitive C-peptide assay
Samples: fasting blood (serum)
Measured: baseline, 1 year, 2 years
Change in prevalence of impaired awareness of hypoglycaemia between baseline and 2-year timepoint as measured by adapted Clarke hypoglycaemia awareness survey
Correlation with C-peptide and clinical parameters
Measured: baseline, 2 years
Genome-wide Association Study (GWAS) by Illumina 720k chip
Measured: cross-sectional: baseline
Assessment of glucagon response after stimulation with a mixed meal tolerance test as measured by the Mercodia glucagon assay (ELISA)
Measured: baseline
Change in patient-reported outcomes between baseline and 2 year timepoint as measured by WHO-5, PAID-20 and WHOQOL surveys
Quality of Life and problem areas in diabetes
Measured: baseline, 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2021
- Study start8 Jun 2016
- Primary completion31 Dec 2021
- Study completion31 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Type 1 DiabetesStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 611 participants (actual)
Sponsor and investigators
- Lead sponsor
- Diabeter Nederland BV
- Sponsor type
- University, hospital or other
- Collaborators
- University Medical Center Groningen
- Responsible party
- Sponsor
- Investigators
- Henk-Jan Aanstoot, MD PhD, Principal investigator, Diabeter Nederland BVBruce HR Wolffenbuttel, MD PhD, Principal investigator, University Medical Center GroningenNel PH Geelhoed-Duijvestijn, MD PhD, Principal investigator, Haaglanden Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04977635
- Sponsor's protocol ID
- NL50314.042.15 / METc 2015/493
- Other IDs
- 3-SRA-2014-291-M-R
- Status last verified
- Mar 2022
- First submitted
- 13 Jul 2021
- Last updated
- 23 Mar 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Varkevisser RDM, Sas T, Aanstoot HJ; Dutch type 1 Biomarker group; Wolffenbuttel BHR, van der Klauw MM. Residual C-peptide is associated with new and persistent impaired awareness of hypoglycaemia in type 1 diabetes. J Diabetes Complications. 2024 Dec;38(12):108893. doi: 10.1016/j.jdiacomp.2024.108893. Epub 2024 Oct 22.
PubMed 39500130Aanstoot HJ, Varkevisser RDM, Mul D, Dekker P, Birnie E, Boesten LSM, Brugts MP, van Dijk PR, Duijvestijn PHLM, Dutta S, Fransman C, Gonera RK, Hoogenberg K, Kooy A, Latres E, Loves S, Nefs G, Sas T, Vollenbrock CE, Vosjan-Noeverman MJ, de Vries-Velraeds MMC, Veeze HJ, Wolffenbuttel BHR, van der Klauw MM; Dutch Type 1 Diabetes Biomarker group. Cohort profile: the 'Biomarkers of heterogeneity in type 1 diabetes' study-a national prospective cohort study of clinical and metabolic phenotyping of individuals with long-standing type 1 diabetes in the Netherlands. BMJ Open. 2024 Jun 19;14(6):e082453. doi: 10.1136/bmjopen-2023-082453.
PubMed 38904129
Study at a glance
From the registry record, last updated by the sponsor on 23 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Biomarkers of Heterogeneity in Type 1 Diabetes: an Integrated Approach to Clinical and Metabolic Phenotyping of Individuals With Established Type 1 Diabetes
- ClinicalTrials.gov ID
- NCT04977635
- Acronym / sponsor ID
- NL50314.042.15 / METc 2015/493
- Conditions
- Type 1 Diabetes
- Keywords
- Heterogeneity, Biomarkers, C-peptide, Glucagon, Impaired awareness of hypoglycemia, Mixed meal tolerance test, Genetics
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 611 participants (actual)
- Lead sponsor
- Diabeter Nederland BVUniversity, hospital or other
- Collaborators
- University Medical Center Groningen
- Study start
- 8 Jun 2016 (actual)
- Primary completion
- 31 Dec 2021 (actual)
- Study completion
- 31 Dec 2021 (actual)
- First posted
- 27 Jul 2021 (actual)
- 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.
Biomarkers of heterogeneity in type 1 diabetes: establishment of a biobank and an integrated approach to clinical and metabolic phenotyping of individuals with established T1DM. In this project the investigators are searching for biomarkers in 600 patients with established (>5 years) diabetes. The inter-relation and patterns of expression in clinical, (auto)immune, metabolic, inflammatory and other parameters, and (potential) biomarkers are investogated. Blood and urine samples are collected annually (over 3 years) in standardized conditions and biobanked. In addition, 150 patients will undergo additional metabolic testing (such as mixed meal-tests).
Detailed description
Identifying biomarkers of type 1 diabetes heterogeneity can help to stage the disease, and identify risks such as the early development of damage and complications.
Type 1 diabetes has long been considered to be an autoimmune disease in which failure of immune tolerance induces a specific immune attack on insulin-producing beta-cells. Recent research shows that the pathophysiology of type 1 diabetes is heterogeneous, involving various beta-cell-specific processes, different genetic predispositions, and several disease stages. It is very important to recognize this heterogeneity as it results in an accumulation of differences in outcomes during the course of the disease.
This heterogeneity requires further elucidation as a heterogeneous disease is likely to require multiple approaches to stop or cure the pathophysiological pathways. This underscores the need for more biomarkers to identify this heterogeneity, the different phases of disease and the effects of interventions and cures.
In many countries and research groups, data and samples from newly-diagnosed individuals (i.e. within the first 6 months after diagnosis) have been collected and studied. Fewer data and samples are available from patients with longer disease duration. This prompted JDRF to grant a strategic research agreement (SRA) to Diabeter and UMC Groningen. Both clinics have access to a substantial clinical database since 1998 with medical record data of > 3500 type 1 diabetes patients.
In this BIOMARKER project, the investigators intend to analyze hormonal, biochemical, immunological, inflammatory and psychological biomarkers of type 1 diabetes in patients with a disease duration of > 5 years. A sample repository (serum, plasma, urine, DNA, RNA) is established which is also accessible to other interested collaborators.
The collection currently includes:
- Fasting samples (serum, plasma, urine, DNA, RNA) from 600 patients with type 1 diabetes (> 5 years duration) taken annually at 3 timepoints
- Samples from 150 patients who underwent Mixed Meal Tolerance Tests (MMTT with 5 timepoints) at 2 occasions (1-year interval)
- Data from questionnaires on psychosocial burden, quality of life, neuropathy and hypoglycaemia completed by the patients
- Clinical datasets on their health, diabetes history, family history and clinical course during treatment
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 600-cohort | – | –Patients with long-term (> 5 years) type 1 diabetes aged 16 years and older As this is an observational study there is no intervention. |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients with >= 5 years duration of type 1 diabetes, age >= 16 years, treated for type 1 diabetes at a diabetes center participating in this study
Key inclusion criteria (5 listed)
- Type 1 diabetes determined by either autoantibodies or based on clinical and historical data or both
- At least 5 years (1825 days) of type 1 diabetes
- Minimum age 16 years
- Treated for type 1 diabetes at a diabetes center participating in this study
- Subject understands study protocol and agrees to comply with it and has been able to read the patient information sheet, has had time to ask questions and get answers and gives signed informed consent.
Key exclusion criteria (7 listed)
- Non-type 1 diabetes
- Patients with a duration of type 1 diabetes below 5 years
- Patients under the age of 16 years
- Pregnancy and breastfeeding, until 3 months (12 weeks) after childbirth or breastfeeding
- On experimental medication or participating in other studies with conflicting goals and schedules
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Change from baseline remaining C-peptide production at 1 year and 2 years as measured by the Beckman ultrasensitive C-peptide assay
Time frame: baseline, 1 year, 2 years
Samples: fasting blood (serum)
Change in prevalence of impaired awareness of hypoglycaemia between baseline and 2-year timepoint as measured by adapted Clarke hypoglycaemia awareness survey
Time frame: baseline, 2 years
Correlation with C-peptide and clinical parameters
Genome-wide Association Study (GWAS) by Illumina 720k chip
Time frame: cross-sectional: baseline
Assessment of glucagon response after stimulation with a mixed meal tolerance test as measured by the Mercodia glucagon assay (ELISA)
Time frame: baseline
Change in patient-reported outcomes between baseline and 2 year timepoint as measured by WHO-5, PAID-20 and WHOQOL surveys
Time frame: baseline, 2 years
Quality of Life and problem areas in diabetes
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 23 Mar 2022.
- Derived from this study: PubMed 39500130Varkevisser RDM, Sas T, Aanstoot HJ; Dutch type 1 Biomarker group; Wolffenbuttel BHR, van der Klauw MM. Residual C-peptide is associated with new and persistent impaired awareness of hypoglycaemia in type 1 diabetes. J Diabetes Complications. 2024 Dec;38(12):108893. doi: 10.1016/j.jdiacomp.2024.108893. Epub 2024 Oct 22.
- Derived from this study: PubMed 38904129Aanstoot HJ, Varkevisser RDM, Mul D, Dekker P, Birnie E, Boesten LSM, Brugts MP, van Dijk PR, Duijvestijn PHLM, Dutta S, Fransman C, Gonera RK, Hoogenberg K, Kooy A, Latres E, Loves S, Nefs G, Sas T, Vollenbrock CE, Vosjan-Noeverman MJ, de Vries-Velraeds MMC, Veeze HJ, Wolffenbuttel BHR, van der Klauw MM; Dutch Type 1 Diabetes Biomarker group. Cohort profile: the 'Biomarkers of heterogeneity in type 1 diabetes' study-a national prospective cohort study of clinical and metabolic phenotyping of individuals with long-standing type 1 diabetes in the Netherlands. BMJ Open. 2024 Jun 19;14(6):e082453. doi: 10.1136/bmjopen-2023-082453.
- Individual participant dataSharing planned: Undecided
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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.
Henk-Jan Aanstoot, MD PhD principal investigator
Diabeter Nederland BV
Bruce HR Wolffenbuttel, MD PhD principal investigator
University Medical Center Groningen
Nel PH Geelhoed-Duijvestijn, MD PhD principal investigator
Haaglanden Medical Center
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Type 1 Diabetes, run by Diabeter Nederland BV at 3 sites in Netherlands.
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 5 inclusion and 7 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 23 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Netherlands. 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?
Change from baseline remaining C-peptide production at 1 year and 2 years as measured by the Beckman ultrasensitive C-peptide assay (time frame: baseline, 1 year, 2 years). The study lists 5 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 NCT04977635, which also lists 2 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 23 Mar 2022.