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Sleep Apnea, Subclinical Coronary Atherosclerosis and Heart Failure in Diabetes Patients With Nephropathy (SLEEP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04549324
Recruitment Status : Recruiting
First Posted : September 15, 2020
Last Update Posted : September 15, 2020
Sponsor:
Information provided by (Responsible Party):
University of Aarhus

Brief Summary:

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 subclinical 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 subclinical 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 of subclinical coronary calcification and subjacent 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 subjacent cardiovascular disease even though the patients don't display any symptoms of either cardiovascular disease or sleep apnea.


Condition or disease
Sleep Apnea Diabetic Nephropathy Type 2 Coronary Atheroscleroses Heart Insufficiency Arterial Stiffness Kidney Diseases Vascular Diseases

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Study Type : Observational
Estimated Enrollment : 80 participants
Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: Sleep Apnea, Subclinical Coronary Atherosclerosis and Heart Failure in Diabetes Patients With Nephropathy
Estimated Study Start Date : September 2020
Estimated Primary Completion Date : August 31, 2021
Estimated Study Completion Date : September 2021

Resource links provided by the National Library of Medicine


Group/Cohort
Sleep Apnea (AHI ≥ 15 per hour)
Patients with moderate/severe sleep apnea (Apnea/hypopnea-index ≥ 15 per hour).
Non-Sleep Apnea (AHI < 5 per hour)
Patients without sleep apnea (Apnea/hypopnea-index < 5 per hour).



Primary Outcome Measures :
  1. The association between sleep apnea and subclinical 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.


  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)

  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´.

  4. The association between sleep apnea and systolic function in patients with diabetic nephropathy. Association between aortic calcification and Left Ventricular Global Longitudinal Strain (GLS) as determined during echocardiography [ 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).


Secondary Outcome Measures :
  1. The association between sleep apnea and coronary plaque volume. [ 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.


  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 patient 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.

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

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

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

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

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

  19. Association between Aorta (sinus valsalva) diameter as determined during echocardiography and sleep apnea in patient 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.

  20. Association between Aorta (Ascendens) diameter as determined during echocardiography and sleep apnea in patient 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.

  21. Association between Aorta (Abdominalis) diameter as determined during echocardiography and sleep apnea in patient 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.

  22. Association between maximum Vena Cava Inferior diameter as determined during echocardiography and sleep apnea in patient 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.

  23. Association between minimum Vena Cava Inferior diameter as determined during echocardiography and sleep apnea in patient 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.

  24. Association between Early mitral inflow velocity (E) as determined during echocardiography and sleep apnea in patient 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.

  25. Association between Late mitral inflow velocity (A) as determined during echocardiography and sleep apnea in patient 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.

  26. Association between E/A-ratio as determined during echocardiography and sleep apnea in patient 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.

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

  28. Association between Right ventricular diameter (RVD) as determined during echocardiography and sleep apnea in patient 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.

  29. Association between left atrial volume (LAV) as determined during echocardiography and sleep apnea in patient 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.

  30. Association between 2D atrial global strain as determined during echocardiography and sleep apnea in patient 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.


Biospecimen Retention:   Samples With DNA
Whole Blood, Plasma, Urine


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Diabetic adult patients (Type 2) with scheduled check-ups at Steno Diabetes Center Aarhus, or Department of Renal Medicine on Aarhus University Hospital can be included in the study if they satisfy all eligible criteria.

The study cohort will consist of:

Generel characteristics of both groups:

- Diabetes Mellitus Type 2 with an eGFR between 10-60 ml/min/1,73 m^2

Sleep Apnea:

  1. 40 patients with an apnea/hyponea-index above ≥ 15 per hour.

    Non-Sleep Apnea:

  2. 40 patients with an apnea/hyponea-index below < 5 per hour.
Criteria

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.
  • Known coronary arterial disease with previous revascularization (PCI or CABG)
  • Known systolic heart failure with an ejection fraction < 45 %. (Estimated within the last 2 years).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04549324


Contacts
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Contact: Niels H. Buus, MD PhD DMSc 454-046-0338 NIBUUS@rm.dk
Contact: Sebastian Nielsen, stud.med 455-188-9528 SEBANE@rm.dk

Locations
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Denmark
Aarhus University Hospital Recruiting
Aarhus, Denmark, 8200
Contact: Sebastian Nielsen, Stud.med    51889528 ext 0045    SEBANE@rm.dk   
Sponsors and Collaborators
University of Aarhus
Investigators
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Study Chair: Niels H. Buus, MD PhD DMSc Department of Renal diseases, Aarhus University Hospital
Principal Investigator: Sebastian Nielsen, Stud.med Department of Renal diseases, Aarhus University Hospital
Study Chair: Jakob T. Nyvad, M.D The Clinic of Hypertension, Aarhus University Hospital
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Responsible Party: University of Aarhus
ClinicalTrials.gov Identifier: NCT04549324    
Other Study ID Numbers: 1-10-72-122-20
First Posted: September 15, 2020    Key Record Dates
Last Update Posted: September 15, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: IPD. pas

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Apnea
Sleep Apnea Syndromes
Kidney Diseases
Diabetic Nephropathies
Heart Failure
Atherosclerosis
Vascular Diseases
Coronary Artery Disease
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Urologic Diseases
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Wake Disorders
Nervous System Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Coronary Disease