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ElectrocardiographyHypoArrhythNCT02315300

Predicting Hypoglycaemia and Arrhythmias in the Vulnerable Patient With Diabetes and Chronic Kidney Disease

A study testing medilog® DARWIN FD12 and Continuous Glucose Monitoring in people with Electrocardiography, run by RWTH Aachen University at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Patients with insulin-dependent diabetes mellitus (DM) and chronic kidney disease (CKD) exhibit an excessive risk for cardiac arrhythmias, in particular sudden cardiac death (SCD). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Electrocardiography
What is being tested?
medilog® DARWIN FD12 and Continuous Glucose Monitoring
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
62 participants
Where
1 siteGermany
Study dates
Nov 2014to May 2016
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Insulin-treated diabetes mellitus (type 1 or 2)
  • CKD with eGFR < 40 ml/min (determined using the MDRD formula)
  • Stable anti-diabetic and cardiac medication prior to inclusion
  • Male or female aged > 18 years
  • Written informed consent prior to study participation

Who cannot join

  • Pregnancy or women without sufficient contraception, adapted specifically to amenorrhoic hemodialysis patients
  • Life expectancy below 6 months
  • Participation in another clinical trial within the previous 2 months
  • History of any other illness, which, in the opinion of the investigator, might pose an unacceptable risk when administering study medication
  • Any current or past medical condition and/or required medication to treat a condition that could affect the evaluation of the study
  • Alcohol or drug abuse
Show all 10Show fewer
  • Patient has been committed to an institution by legal or regulatory order
  • Expected non-compliance
  • Patients unwilling or unable to give informed consent, or with limited ability to comply with instructions for this study
  • Participation in a parallel interventional clinical trial

Trial locations and contacts

1 site in 1 country.

Germany1 site
  • Medizinische Klinik I

    Aachen, North Rhine-Westphalia, 52074

Other trials in Germany

About this study

Patients with insulin-dependent diabetes mellitus (DM) and chronic kidney disease (CKD) exhibit an excessive risk for cardiac arrhythmias, in particular sudden cardiac death (SCD). Hypoglycemia is a frequent problem in insulin-treated patients, especially in those with CKD, and various studies have shown that hypoglycemic episodes are strong predictors of cardiovascular mortality in both type 1 and type 2 diabetic patients. Experimental data and small clinical studies link hypoglycemia with ECG changes and SCD, but little is known about the direct association of hypoglycemic events and/or rapid swings in blood glucose with arrhythmias in this high risk population. Ideally, an algorithm should help to identify patients at risk for hypoglycemia-associated arrhythmias and SCD, but hitherto systematic analyses of blood glucose values and 12-channel ECGs are lacking in these patients.

Read the detailed description

Patients with diabetes mellitus (DM), especially those with a long duration of diabetes, insulin treatment and chronic kidney disease (CKD) are vulnerable patients exhibiting a high risk for cardiac arrhythmias and sudden cardiac death (SCD) [1, 2]. Various factors such as the presence of coronary heart disease, diabetic cardiomyopathy as well autonomic neuropathy are underlying pathologies associated with the development of potentially fatal arrhythmias in these patients while hypoglycemic events are considered to directly trigger these arrhythmias. In 1991, Tattersall and colleagues were the first to describe the phenomenon of sudden nocturnal death in young patients with type 1 diabetes and reported that many of these patients had recent nocturnal hypoglycemia episodes [3]. Therefore it has been postulated that severe hypoglycemia may lead to cardiac arrhythmias, later summarized as the "dead in bed" syndrome [4]. In addition, recent data from large cardiovascular outcome trials in patients with type 2 diabetes suggest that severe hypoglycemia is associated with an increased risk of cardiovascular events and cardiovascular related death [5]. Moreover, CKD markedly increases the risk for hypoglycemia and even a moderate impairment of kidney function (eGFR < 60 ml/min) is associated with a significant increase in SCD [6].

Various pathophysiological mechanisms may contribute to the increased cardiovascular mortality after hypoglycemia including hypoglycemia-induced release of catecholamines, pro-arrhythmogenic ECG alterations, inflammatory changes, direct effects in the vascular wall such as impaired endothelial function as well as abnormalities in coagulation and platelet function [7, 8].

Morphological and functional alterations of the heart occurring in CKD further contribute to these mechanisms. Several small studies performing simultaneous glucose monitoring and ECG recordings addressed the question whether spontaneous hypoglycemic events in patients with diabetes directly lead to cardiac arrhythmias [9-11], but hitherto no clear association has been found. These studies were limited by a short duration of glucose and ECG monitoring and by the fact that only 3 lead Holter-ECGs were used, thus not allowing the assessment of more sophisticated ECG abnormalities such as QT dispersion, T-wave alternans, or late potentials. Therefore no clear data exist to predict arrhythmias and SCD and its relation to hypoglycemia in patients with diabetes. Ideally, a SCD risk score could identify and characterize high-risk patients but to date little is known about hypoglycemia-associated ECG markers for the identification of patients at risk for arrhythmias and SCD.

In the general population, various ECG risk markers for SCD have been identified such as heart rate, cardiac rhythm abnormalities, AV block, QT length, QT dispersion, heart-rate variability (HRV), T-wave alternans, late potentials, as well as left- (LBBB) or right-bundle branch block (RBBB) (reviewed in [12]). In patients with diabetes hypoglycemia, diabetic cardiomyopathy, as well as the presence of autonomic neuropathy may lead to such ECG abnormalities. Under experimental conditions some of these ECG surrogate parameters have been studied in patients with diabetes in association with hypoglycemia. As such, clamp studies revealed that hypoglycemia prolongs the QT interval and increases QT dispersion (difference between the longest and shortest QT interval in a 12-lead Holter ECG) [10, 13], which in conjunction with an increased release of catecholamines during hypoglycemia may promote ventricular arrhythmias. In addition, controlled hypoglycemia in patients with type 1 diabetes alters cardiac repolarization by changing the T-wave amplitude [11]. Sparse data exist on the effect of spontaneous hypoglycemic episodes and changes in ECG parameters with only a small study in patients with type 1 diabetes demonstrating that nocturnal hypoglycemia is associated with a decrease in the low-frequency component of heart rate variability [14]. To date, more sophisticated markers such as QT dispersion (difference between the longest and shortest QT interval in a 12-lead Holter ECG), late potentials, or T-wave alternans (periodic beat-to-beat variation in the morphology, amplitude or timing of the T waves in ECGs) were not examined in a "real-life setting", most likely because these markers require a 12 lead ECG registration of longer duration.

However, for the establishment of a risk algorithm for the prediction of hypoglycemia-associated arrhythmias it is mandatory to perform long duration simultaneous glucose monitoring and 12 lead ECG registration to capture these ECG risk markers for SCD.

Being tested
medilog® DARWIN FD12, Continuous Glucose Monitoring
Keywords
ECG, CGM, Hypoglycaemia, Sudden Cardiac Death
Medical subject headings
Hypoglycemia, Death, Sudden, Cardiac

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • medilog® DARWIN FD12Device

    Also called ECG

  • Continuous Glucose MonitoringDevice

    Also called CGM

Study groups in NCT02315300
Study groupRoleWhat they receive
Study TretamentExperimentalLong term ECG measurement is performed with the 12-lead ECG system medilog® DARWIN FD12 from Schillermed to detect different ECG parameter. The continuous glucose monitoring (CGM) system G4 from Dexcom use a tiny sensor inserted under the skin to check glucose levels in tissue fluid. The sensor stays in place for 7 days in parallel to the ECG measurement. A transmitter sends information about glucose levels via radio waves from the sensor to a pagerlike wireless monitor.
Receives: Device: medilog® DARWIN FD12; Device: Continuous Glucose Monitoring

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. heart rate

    Changes of ECG parameters during 7 days long term ECG

    Measured: not a single event or change of the parameter will be assessed after 18 months patterns of this parameter during a 7 days long-term ECG will screened for potential correlation with hypoglycaemic events

  2. cardiac rhythm abnormalities

    Changes of ECG parameters during 7 days long term ECG

    Measured: not a single event or change of the parameter will be assessed after 18 months patterns of this parameter during a 7 days long-term ECG will screened for potential correlation with hypoglycaemic events

  3. AV block

    Changes of ECG parameters during 7 days long term ECG

    Measured: not a single event or change of the parameter will be assessed after 18 months patterns of this parameter during a 7 days long-term ECG will screened for potential correlation with hypoglycaemic events

  4. QT length

    Changes of ECG parameters during 7 days long term ECG

    Measured: not a single event or change of the parameter will be assessed after 18 months patterns of this parameter during a 7 days long-term ECG will screened for potential correlation with hypoglycaemic events

  5. QT dispersion

    Changes of ECG parameters during 7 days long term ECG

    Measured: not a single event or change of the parameter will be assessed after 18 months patterns of this parameter during a 7 days long-term ECG will screened for potential correlation with hypoglycaemic events

  6. heart-rate variability

    Changes of ECG parameters during 7 days long term ECG

    Measured: not a single event or change of the parameter will be assessed after 18 months patterns of this parameter during a 7 days long-term ECG will screened for potential correlation with hypoglycaemic events

  7. T-wave alternans

    Changes of ECG parameters during 7 days long term ECG

    Measured: not a single event or change of the parameter will be assessed after 18 months patterns of this parameter during a 7 days long-term ECG will screened for potential correlation with hypoglycaemic events

  8. late potentials

    Changes of ECG parameters during 7 days long term ECG

    Measured: not a single event or change of the parameter will be assessed after 18 months patterns of this parameter during a 7 days long-term ECG will screened for potential correlation with hypoglycaemic events

  9. left or right bündle branch blocks

    Changes of ECG parameters during 7 days long term ECG

    Measured: not a single event or change of the parameter will be assessed after 18 months patterns of this parameter during a 7 days long-term ECG will screened for potential correlation with hypoglycaemic events

  10. Glucose Levels < 65 mg/dl

    Changes of ECG parameters during 7 days long term ECG

    Measured: not a single event or change of the parameter will be assessed after 18 months patterns of this parameter during a 7 days long-term ECG will screened for potential correlation with hypoglycaemic events

Secondary outcomes (1)
  1. Association anf temporal coincidence of glycemic variability as assessed by changes in glucose excursion as well as mean amplitude of glycemic excursion (MAGE)

    • occurence of clinically relevant hypoglycemia
    • occurence of symptomatic hypotension
    • occurence of hypertensive urgency \& emergency

    Measured: 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Dec 2014 (estimated)
  2. Study startNov 2014
  3. Primary completionMay 2016
  4. Study completionMay 2016

Resources

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
Prevention
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
62 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02315300
Sponsor's protocol ID
14-030
Acronym
HypoArrhyth
Status last verified
May 2016
First submitted
1 Dec 2014
Last updated
15 Jun 2016
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A study testing medilog® DARWIN FD12 and Continuous Glucose Monitoring in people with Electrocardiography, run by RWTH Aachen University at 1 site in Germany.

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 10 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 15 Jun 2016. 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 Germany. 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?

heart rate (time frame: not a single event or change of the parameter will be assessed after 18 months patterns of this parameter during a 7 days long-term ECG will screened for potential correlation with hypoglycaemic events). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 15 Jun 2016.

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