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NCT Number: NCT04549324

Sleep Apnea, Coronary Atherosclerosis and Heart Failure in Diabetes Patients With Nephropathy

Background:

Diabetes, and especially diabetic kidney disease is associated with the development of cardiovascular disease such as calcification in the coronary arteries and heart failure. Sleep apnea is frequent among patients with diabetes and diabetic kidney disease and sleep apnea itself is a solitary risk factor in the development of cardiovascular disease. Nonetheless, sleep apnea is underdiagnosed in diabetes patients because of a discrepancy between sleep apnea severity and actual oxygen deficiency symptoms which makes the diagnosis difficult. For that reason, many diabetics have undiagnosed sleep apnea together with cardiovascular disease. Early discovery of sleep apnea among high risk diabetic patients may therefore be considered crucial before cardiovascular complications develop. For this reason, sleep apnea screening of high-risk diabetics can possibly improve early diagnostics of cardiovascular disease.

Aim:

This study will seek to establish the association between obstructive sleep apnea (OSA) and coronary calcification and heart failure in patients with diabetic kidney disease. The basic hypothesis of the study is that patients with diabetic kidney disease and concurrent OSA have a higher prevalence and severity of coronary calcification and heart failure compared to patients without OSA.

Methods:

Diabetic adult patients with scheduled check-ups at Steno Diabetes Center Aarhus, or Department of Renal Medicine on Aarhus University Hospital will be included in the study.

Firstly, all included patients are screened for sleep apnea with the devices SomnoTouch® and ApneaLink®. Based on the sleep apnea determination; 40 patients with moderate-severe sleep apnea are compared with 40 patients without sleep apnea. In both groups, the patients are examined for calcification in the coronary vessels using a CT-scan while the function of the heart is examined by ultrasound (echocardiography). The stiffness of aorta is measured and performed using radial artery tonometry (SphygmoCor®).

Furthermore, range of blood- and urine samples will be performed

The perspectives are that patients with diabetes should be regularly evaluated for sleep apnea and that patients with moderate/severe sleep apnea should undergo further examination for cardiovascular disease even though the patients don't display any symptoms of either cardiovascular disease or sleep apnea.

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Key information

Conditions

Sleep Apnea Apnea Arterial Occlusive Diseases Arterial Stiffness Arteriosclerosis Cardiovascular Diseases Coronary Artery Disease Coronary Atheroscleroses Coronary Disease Diabetic Nephropathy Type 2 Dyssomnias Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Heart Diseases Heart Failure Heart Insufficiency Kidney Diseases Male Urogenital Diseases Myocardial Ischemia Nervous System Diseases Respiration Disorders Respiratory Tract Diseases Sleep Apnea Syndromes Sleep Disorders, Intrinsic Sleep Wake Disorders Urogenital Diseases Urologic Diseases Vascular Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Aarhus University Hospital

Aarhus, 8200, Denmark

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • ≥ 18 years.
  • Diabetes Mellitus Type 2 with an eGFR between 10-60 ml/min/1,73 m^2 (Equalling CKD-group 3, 4 and 5 non-dialysis).

Exclusion criteria

  • Known sleep apnea in continuous positive airway pressure(CPAP) treatment.
  • Known mild sleep apnea (AHI 5-14) after the sleep apnea measurement.
  • Participants with central apnea (> 50 % of central apnea episodes in the AHI ≥ 15 group.) or Cheyne Stokes after the sleep apnea measurement.
  • < 4 hours of recording (ApneaLink)
  • Known coronary arterial disease with previous revascularization (PCI or CABG)

Treatment and study plan

Primary outcomes

  1. The association between sleep apnea and coronary atherosclerosis (Agatston Score) measured with cardiac CT-scan in patients with diabetic nephropathy.

    Time frame: Cardiac CT-scan will be performed no later than 1 month after inclusion. All Agatston scores will be estimated straight after the cardiac CT-scan.

    The degree of atherosclerosis in the coronary artery walls is evaluated by cardiac CT-scan and subsequent quantified by Agatston score. Patients with an estimated glomerular filtration rate (eGFR) ≤ 25 ml/min/1,73 m2 is scanned without contrast whereas patients with an eGFR 26-60 ml/min/1,73 m2 are screened with contrast.

    All Agatston scoring will be performed by a cardiologist blinded to information on patient biochemical characteristics and AHI. The only biochemical parameter which the cardiologist is not blinded to is eGFR.

  2. The association between sleep apnea and systolic function in patients with diabetic nephropathy.

    Time frame: Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan

    All patients included in the study will undergo transthoracic echocardiography. Systolic function is evaluated by two-dimensional automated evaluation of ejection fraction (2-D auto-EF).

    The echocardiographic-clinician is blinded to AHI-status.

  3. The association between sleep apnea and diastolic heart failure in patients with diabetic nephropathy.

    Time frame: Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan

    All patients included in the study will undergo transthoracic echocardiography. Diastolic function is evaluated by E/e´.

    The echocardiographic-clinician is blinded to AHI-status.

  4. The association between sleep apnea and systolic function in patients with diabetic nephropathy.

    Time frame: Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan

    All patients included in the study will undergo transthoracic echocardiography. Systolic function is evaluated by Left Ventricular Global Longitudinal Strain (GLS).

    The echocardiographic-clinician is blinded to AHI-status.

Secondary outcomes

  1. The association between sleep apnea and coronary plaque volume in patients with diabetic nephropathy.

    Time frame: Cardiac CT-scan will be performed no later than 1 month after inclusion.

    Coronary plaque volume is estimated by a cardiac CT-scan with contrast.

    All coronary plaque volume analysing will be performed by a cardiologist blinded to information on patient biochemical characteristics and AHI. The only biochemical parameter which the cardiologist is not blinded to is eGFR.

  2. Association of sleep apnea and aortic stiffness (defined as Pulse Wave Velocity (PWV)) in patients with diabetic nephropathy.

    Time frame: PWV is performed the same day as the patient is included.

    To get a non-invasive estimate of the aortic stiffness, measurement of Pulse Wave Velocity (PWV) (carotid-femoral and carotid-radial) will be performed. PWV will be recorded with the Sphygmocor® device according to regular protocol. If possible, two acceptable measurements will be conducted for each included patient. Calculation of PWV will be performed automatically by the device using a previously published formula.

  3. Association between Matrix Gla Protein (MGP) and coronary calcification in patients with sleep apnea and diabetic nephropathy.

    Time frame: Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021

    To establish a deeper understanding of the pathogenesis of central arterial calcification in patients with sleep apnea and diabetic nephropathy. MGP, a novel biochemical marker of arterial calcification, will be collected and analysed in all patients.

  4. Association between Calcification propensity score (T50test) and coronary calcification in patients with sleep apnea and diabetic nephropathy.

    Time frame: Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021

    To establish a deeper understanding of the pathogenesis of central arterial calcification in patients with sleep apnea and diabetic nephropathy. Calcification propensity score (T50test) will be collected and analysed in all patients.

  5. Association between sRANKL (soluble receptor activator of nuclear factor kappa-B ligand) and coronary calcification in patients with sleep apnea and diabetic nephropathy.

    Time frame: Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021

    To establish a deeper understanding of the pathogenesis of central arterial calcification in patients with sleep apnea and diabetic nephropathy. sRANKL (soluble receptor activator of nuclear factor kappa-B ligand) will be collected and analysed in all patients.

  6. Association between 25-OH-Vitamin D(D3+D2) and coronary calcification in patients with sleep apnea and diabetic nephropathy.

    Time frame: Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021

    To establish a deeper understanding of the pathogenesis of central arterial calcification in patients with sleep apnea and diabetic nephropathy. 25-OH-Vitamin D(D3+D2) will be collected and analysed in all patients.

  7. Association between Fetuin-A(alfa-2-Heremans Schmid glycoprotein; AHSG) and coronary calcification in patients with sleep apnea and diabetic nephropathy.

    Time frame: Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021.

    To establish a deeper understanding of the pathogenesis of central arterial calcification in patients with sleep apnea and diabetic nephropathy. Fetuin-A(alfa-2-Heremans Schmid glycoprotein; AHSG) will be collected and analysed in all patients

  8. Association between Sclerostin and coronary calcification in patients with sleep apnea and diabetic nephropathy.

    Time frame: Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021

    To establish a deeper understanding of the pathogenesis of central arterial calcification in patients with sleep apnea and diabetic nephropathy., Sclerostin will be collected and analysed in all patients

  9. Association between osteoprotegerin and coronary calcification in patients with sleep apnea and diabetic nephropathy.

    Time frame: Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021

    To establish a deeper understanding of the pathogenesis of central arterial calcification in patients with sleep apnea and diabetic nephropathy., osteoprotegerin will be collected and analysed in all patients.

  10. Association between BsAP (bone-specific alkaline phosphatase) and coronary calcification in patients with sleep apnea and diabetic nephropathy.

    Time frame: Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021

    To establish a deeper understanding of the pathogenesis of central arterial calcification in patients with sleep apnea and diabetic nephropathy., BsAP (bone-specific alkaline phosphatase) will be collected and analysed in all patients

  11. Association between TRAP5B (tartrate-resistant acid phosphatase 5b) and coronary calcification in patients with sleep apnea and diabetic nephropathy.

    Time frame: Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021

    To establish a deeper understanding of the pathogenesis of central arterial calcification in patients with sleep apnea and diabetic nephropathy, TRAP5B (tartrate-resistant acid phosphatase 5b) will be collected and analysed in all patients.

  12. Association between P1NP (procollagen type 1 N propeptide) and coronary calcification in patients with sleep apnea and diabetic nephropathy.

    Time frame: Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021

    To establish a deeper understanding of the pathogenesis of central arterial calcification in patients with sleep apnea and diabetic nephropathy., P1NP (procollagen type 1 N propeptide) will be collected and analysed in all patients

  13. Association between LVEDd (Left ventricular end diastolic diameter) as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.

    Time frame: Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan

    All patients included in this study will undergo echocardiography. In particular systolic and diastolic function will be in focus.

    The echocardiographic-clinician is blinded to AHI-status.

  14. Association between LVEDs (Left ventricular end systolic diameter) as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.

    Time frame: Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan

    All patients included in this study will undergo echocardiography. In particular systolic and diastolic function will be in focus.

    The echocardiographic-clinician is blinded to AHI-status.

  15. Association between IVSd (Interventricular Septal Thickness at Diastole) as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.

    Time frame: Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan

    All patients included in this study will undergo echocardiography. In particular systolic and diastolic function will be in focus.

    The echocardiographic-clinician is blinded to AHI-status.

  16. Association between IVSs (Interventricular Septal Thickness at Systole) as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.

    Time frame: Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan

    All patients included in this study will undergo echocardiography. In particular systolic and diastolic function will be in focus.

    The echocardiographic-clinician is blinded to AHI-status.

  17. Association between PWTd (Posterior wall thickness at end-diastole) as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.

    Time frame: Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan

    All patients included in this study will undergo echocardiography. In particular systolic and diastolic function will be in focus.

    The echocardiographic-clinician is blinded to AHI-status.

  18. Association between PWTs (Posterior wall thickness at end-systole) as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.

    Time frame: Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan

    All patients included in this study will undergo echocardiography. In particular systolic and diastolic function will be in focus.

    The echocardiographic-clinician is blinded to AHI-status.

  19. Association between Aorta (sinus valsalva) diameter as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.

    Time frame: Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan

    All patients included in this study will undergo echocardiography. In particular systolic and diastolic function will be in focus.

    The echocardiographic-clinician is blinded to AHI-status.

  20. Association between Aorta (Ascendens) diameter as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.

    Time frame: Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan

    All patients included in this study will undergo echocardiography. In particular systolic and diastolic function will be in focus.

    The echocardiographic-clinician is blinded to AHI-status.

  21. Association between Aorta (Abdominalis) diameter as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.

    Time frame: Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan

    All patients included in this study will undergo echocardiography. In particular systolic and diastolic function will be in focus.

    The echocardiographic-clinician is blinded to AHI-status.

  22. Association between maximum Vena Cava Inferior diameter as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.

    Time frame: Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan

    All patients included in this study will undergo echocardiography. In particular systolic and diastolic function will be in focus.

    The echocardiographic-clinician is blinded to AHI-status.

  23. Association between minimum Vena Cava Inferior diameter as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.

    Time frame: Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan

    All patients included in this study will undergo echocardiography. In particular systolic and diastolic function will be in focus.

    The echocardiographic-clinician is blinded to AHI-status.

  24. Association between Early mitral inflow velocity (E) as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.

    Time frame: Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan

    All patients included in this study will undergo echocardiography. In particular systolic and diastolic function will be in focus.

    The echocardiographic-clinician is blinded to AHI-status.

  25. Association between Late mitral inflow velocity (A) as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.

    Time frame: Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan

    All patients included in this study will undergo echocardiography. In particular systolic and diastolic function will be in focus.

    The echocardiographic-clinician is blinded to AHI-status.

  26. Association between E/A-ratio as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.

    Time frame: Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan

    All patients included in this study will undergo echocardiography. In particular systolic and diastolic function will be in focus.

    The echocardiographic-clinician is blinded to AHI-status.

  27. Association between Deceleration time of early diastolic transmittal flow (dtE) as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.

    Time frame: Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan

    All patients included in this study will undergo echocardiography. In particular systolic and diastolic function will be in focus.

    The echocardiographic-clinician is blinded to AHI-status.

  28. Association between Right ventricular diameter (RVD) as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.

    Time frame: Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan

    All patients included in this study will undergo echocardiography. In particular systolic and diastolic function will be in focus.

    The echocardiographic-clinician is blinded to AHI-status.

  29. Association between left atrial volume (LAV) as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.

    Time frame: Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan

    All patients included in this study will undergo echocardiography. In particular systolic and diastolic function will be in focus. The echocardiographic-clinician is blinded to AHI-status.

  30. Association between 2D atrial global strain as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.

    Time frame: Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan

    All patients included in this study will undergo echocardiography. In particular systolic and diastolic function will be in focus. The echocardiographic-clinician is blinded to AHI-status.

Sponsors and collaborators

Lead sponsor

University of Aarhus

Other

Registry information

Acronym: SLEEP

Important dates

Study start
2020
Primary completion
2022
Study completion
2022
First posted
Sep 16, 2020
Registry last updated
Feb 7, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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