Activation Innate Immune System in Type 1 Diabetes

March 29, 2019 updated by: Radboud University Medical Center

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.

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 Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
66

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Nijmegen, Netherlands, PO BOX 9101, 6500 HB
        • Radboud University Nijmegen Medical Centre, Department of Internal Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

20 years to 60 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Type 1 diabetes patients, without macrovascular complications. Minimum diabetes duration 10 years.

Patients are recruited at university hospital.

Description

Inclusion Criteria:

  • 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
  • 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

Exclusion Criteria:

  • 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
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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
Radiation: PET-CT (positron emission tomography - computer tomography)
PET-CT to determine vascular inflammation
Diagnostic test: Blood drawn
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
Radiation: PET-CT (positron emission tomography - computer tomography)
PET-CT to determine vascular inflammation
Diagnostic test: Blood drawn
Blood drawn
Healthy subjects
  • Absence of disease, no use of medication
  • Matched for age, gender and BMI
  • HbA1c <42 mmol/mol
Radiation: PET-CT (positron emission tomography - computer tomography)
PET-CT to determine vascular inflammation
Diagnostic test: Blood drawn
Blood drawn

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
through study completion, within 1 year

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
FDG (fluorodeoxyglucose) uptake in spleen and bone marrow, measured by 18F-FDG-PET/CT.
Time Frame: through study completion, within 1 year
Measurement of FDG uptake in bone marrow and spleen.
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.
Blood will be collected for all subjects. LPS induced TNF production
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
Measurement of mitochondrial stress test = oxygen consumption rate (OCR)
within 1 day after inclusion
Epigenetic changes
Time Frame: Within 2 months after inclusion
Measurement of epigenetic changes by ChIP-seq (chromatin immunoprecipitation)
Within 2 months after inclusion
Arterial wall inflammation, measured by 18F-FDG-PET/CT
Time Frame: through study completion, within 1 year
Compare arterial wall inflammation between diabetes patients and healthy subjects. Comparison by using TBR (see description Outcome 1).
through study completion, within 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Radboud University Medical Center

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
European Foundation for the Study of Diabetes

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 18, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 21, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 21, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 22, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 15, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 22, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 2, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 29, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NL62200.091.17

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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