Diabetes Mellitus, Type 1NCT03441919
Activation Innate Immune System in Type 1 Diabetes
An observational study of Diabetes Mellitus, Type 1 and Cardiovascular Diseases, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
Hyperglycemia is a well-known cardiovascular risk factor. It has also been shown that episodes of hyperglycemia increase the risk for cardiovascular diseases despite return to normoglycemia, a phenomenon termed 'glycemic or metabolic memory'. The molecular mechanism underlying this phenomenon remains unclear. Read more about this study
- Who is it for?
- Ages 20 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Diabetes Mellitus, Type 1, Cardiovascular Diseases, Innate Immune System
- What is being tested?
- PET-CT (positron emission tomography - computer tomography) and Blood drawn
- Type of treatment
- Surgery or procedure
- How many people
- 66 participants
- Where
- 1 siteNetherlands
- Study dates
- 18 Jan 2018to 21 Jan 2019
- 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 20 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Study population: Type 1 diabetes patients, without macrovascular complications. Minimum diabetes duration 10 years. Patients are recruited at university hospital.
Who may be able to join
- Group 1 and 2 (patients with type 1 diabetes):
- Diagnosis based on clinical criteria
- Duration of diabetes ≥10 years
- Age ≥20 years, ≤ 60 years
- Group 1: HbA1c >64 mmol/mol
- Group 2: HbA1c ≤64 mmol/mol
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- Written informed consent
- Group 3 (healthy controls):
- Absence of disease, no use of medication
- Matched for age, gender and BMI
- HbA1c <42 mmol/mol
- Written informed consent
Who cannot join
- Inability to provide informed consent
- Smoking
- Specific Medication use:
- Use of immunosuppressive drugs
- Use of statins < 2 weeks before performing PET-CT (Those that use statins will be asked to discontinue for two weeks. This can be safely done in the context of primary prevention.)
- Use of acetylsalicylic acid
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- Previous cardiovascular events (ischemic stroke/TIA (transient ischemic attack), myocardial infarction, peripheral arterial disease)
- Auto-inflammatory or auto-immune diseases
- Current or recent infection (< 3 months)
- Previous vaccination (< 3 months)
- Renal failure (MDRD <45)
- BMI>30 kg/m2
- Pregnancy
- Claustrophobia
- Severe hypoglycaemia < 1 week before PET-CT
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Radboud University Nijmegen Medical Centre, Department of Internal Medicine
Nijmegen, PO BOX 9101, 6500 HB
About this study
Official title: Activation of the Innate Immune System and Vascular Inflammation in Patients With Type 1 Diabetes
Hyperglycemia is a well-known cardiovascular risk factor. It has also been shown that episodes of hyperglycemia increase the risk for cardiovascular diseases despite return to normoglycemia, a phenomenon termed 'glycemic or metabolic memory'. The molecular mechanism underlying this phenomenon remains unclear.
Cardiovascular events, such as myocardial infarction and stroke are caused by atherosclerosis, which is characterized by low grade inflammation of the vascular wall, including accumulation of innate immune cells such as monocytes and macrophages.
Read more
The investigators hypothesize that chronic hyperglycemia shifts intracellular metabolism of innate immune cells towards glycolysis and changes the epigenetic state of (progenitors of) innate immune cells (monocytes and macrophages), which reprograms these cells towards a more aggressive, pro-atherogenic phenotype, thereby accelerating atherosclerosis.
In this study, the investigators aim to test this hypothesis. This research will reveal whether the innate immune cells of patients with chronic hyperglycemia show a durable shift in intracellular metabolism and epigenetic changes and whether this associates with vascular inflammation.
- Conditions
- Diabetes Mellitus, Type 1, Cardiovascular Diseases, Innate Immune System, Inflammation, Metabolism Disorder, Glucose
- Being tested
- PET-CT (positron emission tomography - computer tomography), Blood drawn
- Medical subject headings
- Diabetes Mellitus, Type 1, Cardiovascular Diseases, Inflammation, Glucose Metabolism Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PET-CT (positron emission tomography - computer tomography)Radiation
PET-CT to determine vascular inflammation
Blood drawnDiagnostic test
Blood drawn
| Study group | Role | What they receive |
|---|---|---|
| Patients with type 1 diabetes, poor glycemic control | * Diagnosis based on clinical criteria
* Duration of diabetes ≥10 years
* Age ≥20 years, ≤ 60 years
* HbA1c >64 mmol/mol Receives: Radiation: PET-CT (positron emission tomography - computer tomography); Diagnostic Test: Blood drawn | |
| Patients with type 1 diabetes, good glycemic control | * Diagnosis based on clinical criteria
* Duration of diabetes ≥10 years
* Age ≥20 years, ≤ 60 years
* HbA1c <64 mmol/mol Receives: Radiation: PET-CT (positron emission tomography - computer tomography); Diagnostic Test: Blood drawn | |
| Healthy subjects | * Absence of disease, no use of medication
* Matched for age, gender and BMI
* HbA1c <42 mmol/mol Receives: Radiation: PET-CT (positron emission tomography - computer tomography); Diagnostic Test: Blood drawn |
What is being measured
The primary outcome is the main question the study is designed to answer.
Arterial wall inflammation, measured by 18F-FDG-PET/CT
Compare arterial wall inflammation (expressed as target-to-background-ratio (TBR) measured in large arterial vessels) between well- and poorly-controlled patients. The TBR is the ratio of FDG uptake in large arterial and large venous bloodvessels.
Measured: through study completion, within 1 year
Secondary outcomes (5)
FDG (fluorodeoxyglucose) uptake in spleen and bone marrow, measured by 18F-FDG-PET/CT.
Measurement of FDG uptake in bone marrow and spleen.
Measured: through study completion, within 1 year
Inflammatory phenotype
Blood will be collected for all subjects. LPS induced TNF production
Measured: Most measurements within 1 week after inclusion. Cytokine measurements after completion of the inclusion of all patients.
Intracellular metabolism, measured by Seahorse respirometer
Measurement of mitochondrial stress test = oxygen consumption rate (OCR)
Measured: within 1 day after inclusion
Epigenetic changes
Measurement of epigenetic changes by ChIP-seq (chromatin immunoprecipitation)
Measured: Within 2 months after inclusion
Arterial wall inflammation, measured by 18F-FDG-PET/CT
Compare arterial wall inflammation between diabetes patients and healthy subjects. Comparison by using TBR (see description Outcome 1).
Measured: through study completion, within 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Feb 2018
- Study start18 Jan 2018
- Primary completion21 Jan 2019
- Study completion21 Jan 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 1Studies 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
- Case-control
- Time perspective
- Prospective
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- European Foundation for the Study of Diabetes
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03441919
- Sponsor's protocol ID
- NL62200.091.17
- Status last verified
- Mar 2019
- First submitted
- 22 Jan 2018
- Last updated
- 2 Apr 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Thiem K, van Dierendonck XAMH, Janssen AWM, Boogaard JP, Riksen NP, Tack CJ, Stienstra R. A High Glycemic Burden Relates to Functional and Metabolic Alterations of Human Monocytes in Patients With Type 1 Diabetes. Diabetes. 2020 Dec;69(12):2735-2746. doi: 10.2337/db20-0568. Epub 2020 Sep 25.
PubMed 32978233
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Activation of the Innate Immune System and Vascular Inflammation in Patients With Type 1 Diabetes
- ClinicalTrials.gov ID
- NCT03441919
- Acronym / sponsor ID
- NL62200.091.17
- Conditions
- Diabetes Mellitus, Type 1, Cardiovascular Diseases, Innate Immune System, Inflammation, Metabolism Disorder, Glucose
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 66 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- European Foundation for the Study of Diabetes
- Study start
- 18 Jan 2018 (actual)
- Primary completion
- 21 Jan 2019 (actual)
- Study completion
- 21 Jan 2019 (actual)
- First posted
- 22 Feb 2018 (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.
Hyperglycemia is a well-known cardiovascular risk factor. It has also been shown that episodes of hyperglycemia increase the risk for cardiovascular diseases despite return to normoglycemia, a phenomenon termed 'glycemic or metabolic memory'. The molecular mechanism underlying this phenomenon remains unclear.
Cardiovascular events, such as myocardial infarction and stroke are caused by atherosclerosis, which is characterized by low grade inflammation of the vascular wall, including accumulation of innate immune cells such as monocytes and macrophages.
The investigators hypothesize that chronic hyperglycemia shifts intracellular metabolism of innate immune cells towards glycolysis and changes the epigenetic state of (progenitors of) innate immune cells (monocytes and macrophages), which reprograms these cells towards a more aggressive, pro-atherogenic phenotype, thereby accelerating atherosclerosis.
In this study, the investigators aim to test this hypothesis. This research will reveal whether the innate immune cells of patients with chronic hyperglycemia show a durable shift in intracellular metabolism and epigenetic changes and whether this associates with vascular inflammation.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Patients with type 1 diabetes, poor glycemic control | – | Radiation: PET-CT (positron emission tomography - computer tomography), Diagnostic Test: Blood drawn* Diagnosis based on clinical criteria * Duration of diabetes ≥10 years * Age ≥20 years, ≤ 60 years * HbA1c >64 mmol/mol |
| Patients with type 1 diabetes, good glycemic control | – | Radiation: PET-CT (positron emission tomography - computer tomography), Diagnostic Test: Blood drawn* Diagnosis based on clinical criteria * Duration of diabetes ≥10 years * Age ≥20 years, ≤ 60 years * HbA1c <64 mmol/mol |
| Healthy subjects | – | Radiation: PET-CT (positron emission tomography - computer tomography), Diagnostic Test: Blood drawn* Absence of disease, no use of medication * Matched for age, gender and BMI * HbA1c <42 mmol/mol |
Who may qualify
- Ages
- 20 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- Type 1 diabetes patients, without macrovascular complications. Minimum diabetes duration 10 years. Patients are recruited at university hospital.
Key inclusion criteria (12 listed)
- Group 1 and 2 (patients with type 1 diabetes):
- Diagnosis based on clinical criteria
- Duration of diabetes ≥10 years
- Age ≥20 years, ≤ 60 years
- Group 1: HbA1c >64 mmol/mol
Key exclusion criteria (15 listed)
- Inability to provide informed consent
- Smoking
- Specific Medication use:
- Previous cardiovascular events (ischemic stroke/TIA (transient ischemic attack), myocardial infarction, peripheral arterial disease)
- Auto-inflammatory or auto-immune diseases
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 |
|---|---|---|
| PET-CT (positron emission tomography - computer tomography)PET-CT to determine vascular inflammation | Radiation | Healthy subjects, Patients with type 1 diabetes, good glycemic control, Patients with type 1 diabetes, poor glycemic control |
| Blood drawnBlood drawn | Diagnostic test | Healthy subjects, Patients with type 1 diabetes, good glycemic control, Patients with type 1 diabetes, poor glycemic control |
Primary outcome
Arterial wall inflammation, measured by 18F-FDG-PET/CT
Time frame: through study completion, within 1 year
Compare arterial wall inflammation (expressed as target-to-background-ratio (TBR) measured in large arterial vessels) between well- and poorly-controlled patients. The TBR is the ratio of FDG uptake in large arterial and large venous bloodvessels.
5 secondary outcomes
FDG (fluorodeoxyglucose) uptake in spleen and bone marrow, measured by 18F-FDG-PET/CT.
Time frame: through study completion, within 1 year
Inflammatory phenotype
Time frame: Most measurements within 1 week after inclusion. Cytokine measurements after completion of the inclusion of all patients.
Intracellular metabolism, measured by Seahorse respirometer
Time frame: within 1 day after inclusion
Epigenetic changes
Time frame: Within 2 months after inclusion
Arterial wall inflammation, measured by 18F-FDG-PET/CT
Time frame: through study completion, within 1 year
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 2 Apr 2019.
- Derived from this study: PubMed 32978233Thiem K, van Dierendonck XAMH, Janssen AWM, Boogaard JP, Riksen NP, Tack CJ, Stienstra R. A High Glycemic Burden Relates to Functional and Metabolic Alterations of Human Monocytes in Patients With Type 1 Diabetes. Diabetes. 2020 Dec;69(12):2735-2746. doi: 10.2337/db20-0568. Epub 2020 Sep 25.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Diabetes Mellitus, Type 1 and Cardiovascular Diseases, run by Radboud University Medical Center at 1 site 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 12 inclusion and 15 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 2 Apr 2019. 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 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?
Arterial wall inflammation, measured by 18F-FDG-PET/CT (time frame: through study completion, within 1 year). 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 NCT03441919, which also lists 1 linked publication.
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 2 Apr 2019.