Clinical trial NCT04549324: Sleep Apnea, Coronary Atherosclerosis and Heart Failure in Diabetes Patients With Nephropathy
Official title: Sleep Apnea, Coronary Atherosclerosis and Heart Failure in Diabetes Patients With Nephropathy
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Sleep Apnea
Diabetic Nephropathy Type 2
Coronary Atheroscleroses
Heart Insufficiency
Arterial Stiffness
Kidney Diseases
Vascular Diseases
Lead sponsor: University of Aarhus
Sponsor class: OTHER
First posted: 2020-09-16
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
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. Additionally, patients from the GP and within the including area of Aarhus University Hospital were invited to participate in the study.

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.

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 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.


Eligibility 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.
* 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)

Primary outcomes:
measure: The association between sleep apnea and coronary atherosclerosis (Agatston Score) measured with cardiac CT-scan in patients with diabetic nephropathy.
timeFrame: 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.
measure: The association between sleep apnea and systolic function in patients with diabetic nephropathy.
timeFrame: Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan
measure: The association between sleep apnea and diastolic heart failure in patients with diabetic nephropathy.
timeFrame: Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan
measure: The association between sleep apnea and systolic function in patients with diabetic nephropathy.
timeFrame: Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan
Secondary outcomes:
measure: The association between sleep apnea and coronary plaque volume in patients with diabetic nephropathy.
timeFrame: Cardiac CT-scan will be performed no later than 1 month after inclusion.
measure: Association of sleep apnea and aortic stiffness (defined as Pulse Wave Velocity (PWV)) in patients with diabetic nephropathy.
timeFrame: PWV is performed the same day as the patient is included.
measure: Association between Matrix Gla Protein (MGP) and coronary calcification in patients with sleep apnea and diabetic nephropathy.
timeFrame: Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021
measure: Association between Calcification propensity score (T50test) and coronary calcification in patients with sleep apnea and diabetic nephropathy.
timeFrame: Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021
measure: Association between sRANKL (soluble receptor activator of nuclear factor kappa-B ligand) and coronary calcification in patients with sleep apnea and diabetic nephropathy.
timeFrame: Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021
measure: Association between 25-OH-Vitamin D(D3+D2) and coronary calcification in patients with sleep apnea and diabetic nephropathy.
timeFrame: Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021
measure: Association between Fetuin-A(alfa-2-Heremans Schmid glycoprotein; AHSG) and coronary calcification in patients with sleep apnea and diabetic nephropathy.
timeFrame: Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021.
measure: Association between Sclerostin and coronary calcification in patients with sleep apnea and diabetic nephropathy.
timeFrame: Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021
measure: Association between osteoprotegerin and coronary calcification in patients with sleep apnea and diabetic nephropathy.
timeFrame: Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021
measure: Association between BsAP (bone-specific alkaline phosphatase) and coronary calcification in patients with sleep apnea and diabetic nephropathy.
timeFrame: Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021
measure: Association between TRAP5B (tartrate-resistant acid phosphatase 5b) and coronary calcification in patients with sleep apnea and diabetic nephropathy.
timeFrame: Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021
measure: Association between P1NP (procollagen type 1 N propeptide) and coronary calcification in patients with sleep apnea and diabetic nephropathy.
timeFrame: Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021
measure: Association between LVEDd (Left ventricular end diastolic diameter) as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.
timeFrame: Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan
measure: Association between LVEDs (Left ventricular end systolic diameter) as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.
timeFrame: Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan
measure: Association between IVSd (Interventricular Septal Thickness at Diastole) as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.
timeFrame: Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan
measure: Association between IVSs (Interventricular Septal Thickness at Systole) as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.
timeFrame: Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan
measure: Association between PWTd (Posterior wall thickness at end-diastole) as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.
timeFrame: Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan
measure: Association between PWTs (Posterior wall thickness at end-systole) as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.
timeFrame: Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan
measure: Association between Aorta (sinus valsalva) diameter as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.
timeFrame: Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan
measure: Association between Aorta (Ascendens) diameter as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.
timeFrame: Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan
measure: Association between Aorta (Abdominalis) diameter as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.
timeFrame: Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan
measure: Association between maximum Vena Cava Inferior diameter as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.
timeFrame: Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan
measure: Association between minimum Vena Cava Inferior diameter as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.
timeFrame: Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan
measure: Association between Early mitral inflow velocity (E) as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.
timeFrame: Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan
measure: Association between Late mitral inflow velocity (A) as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.
timeFrame: Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan
measure: Association between E/A-ratio as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.
timeFrame: Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan
measure: Association between Deceleration time of early diastolic transmittal flow (dtE) as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.
timeFrame: Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan
measure: Association between Right ventricular diameter (RVD) as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.
timeFrame: Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan
measure: Association between left atrial volume (LAV) as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.
timeFrame: Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan
measure: Association between 2D atrial global strain as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.
timeFrame: Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
Study officials:
affiliation: Department of Renal diseases, Aarhus University Hospital
name: Niels H. Buus, MD PhD DMSc
role: STUDY_CHAIR
affiliation: Department of Renal diseases, Aarhus University Hospital
name: Sebastian Nielsen, MD student
role: PRINCIPAL_INVESTIGATOR
affiliation: The Clinic of Hypertension, Aarhus University Hospital
name: Jakob T. Nyvad, MD
role: STUDY_CHAIR
References: