Sleep Apnea, Coronary Atherosclerosis and Heart Failure in Diabetes Patients With Nephropathy (SLEEP)
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.
調査の概要
研究の種類
入学 (実際)
連絡先と場所
研究場所
-
-
-
Aarhus、デンマーク、8200
- Aarhus University Hospital
-
-
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
サンプリング方法
調査対象母集団
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:
40 patients with an apnea/hyponea-index above ≥ 15 per hour.
Non-Sleep Apnea:
- 40 patients with an apnea/hyponea-index below < 5 per hour.
説明
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)
研究計画
研究はどのように設計されていますか？
デザインの詳細
コホートと介入
グループ/コホート |
|---|
|
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).
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
The association between sleep apnea and coronary atherosclerosis (Agatston Score) measured with cardiac CT-scan in patients with diabetic nephropathy.
時間枠：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. |
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 association between sleep apnea and systolic function in patients with diabetic nephropathy.
時間枠：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. |
Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan
|
|
The association between sleep apnea and diastolic heart failure in patients with diabetic nephropathy.
時間枠：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. |
Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan
|
|
The association between sleep apnea and systolic function in patients with diabetic nephropathy.
時間枠：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. |
Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
The association between sleep apnea and coronary plaque volume in patients with diabetic nephropathy.
時間枠：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. |
Cardiac CT-scan will be performed no later than 1 month after inclusion.
|
|
Association of sleep apnea and aortic stiffness (defined as Pulse Wave Velocity (PWV)) in patients with diabetic nephropathy.
時間枠：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.
|
PWV is performed the same day as the patient is included.
|
|
Association between Matrix Gla Protein (MGP) and coronary calcification in patients with sleep apnea and diabetic nephropathy.
時間枠：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.
|
Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021
|
|
Association between Calcification propensity score (T50test) and coronary calcification in patients with sleep apnea and diabetic nephropathy.
時間枠：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.
|
Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021
|
|
Association between sRANKL (soluble receptor activator of nuclear factor kappa-B ligand) and coronary calcification in patients with sleep apnea and diabetic nephropathy.
時間枠：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.
|
Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021
|
|
Association between 25-OH-Vitamin D(D3+D2) and coronary calcification in patients with sleep apnea and diabetic nephropathy.
時間枠：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.
|
Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021
|
|
Association between Fetuin-A(alfa-2-Heremans Schmid glycoprotein; AHSG) and coronary calcification in patients with sleep apnea and diabetic nephropathy.
時間枠：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
|
Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021.
|
|
Association between Sclerostin and coronary calcification in patients with sleep apnea and diabetic nephropathy.
時間枠：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
|
Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021
|
|
Association between osteoprotegerin and coronary calcification in patients with sleep apnea and diabetic nephropathy.
時間枠：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.
|
Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021
|
|
Association between BsAP (bone-specific alkaline phosphatase) and coronary calcification in patients with sleep apnea and diabetic nephropathy.
時間枠：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
|
Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021
|
|
Association between TRAP5B (tartrate-resistant acid phosphatase 5b) and coronary calcification in patients with sleep apnea and diabetic nephropathy.
時間枠：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.
|
Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021
|
|
Association between P1NP (procollagen type 1 N propeptide) and coronary calcification in patients with sleep apnea and diabetic nephropathy.
時間枠：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
|
Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021
|
|
Association between LVEDd (Left ventricular end diastolic diameter) as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.
時間枠：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. |
Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan
|
|
Association between LVEDs (Left ventricular end systolic diameter) as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.
時間枠：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. |
Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan
|
|
Association between IVSd (Interventricular Septal Thickness at Diastole) as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.
時間枠：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. |
Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan
|
|
Association between IVSs (Interventricular Septal Thickness at Systole) as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.
時間枠：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. |
Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan
|
|
Association between PWTd (Posterior wall thickness at end-diastole) as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.
時間枠：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. |
Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan
|
|
Association between PWTs (Posterior wall thickness at end-systole) as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.
時間枠：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. |
Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan
|
|
Association between Aorta (sinus valsalva) diameter as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.
時間枠：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. |
Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan
|
|
Association between Aorta (Ascendens) diameter as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.
時間枠：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. |
Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan
|
|
Association between Aorta (Abdominalis) diameter as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.
時間枠：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. |
Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan
|
|
Association between maximum Vena Cava Inferior diameter as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.
時間枠：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. |
Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan
|
|
Association between minimum Vena Cava Inferior diameter as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.
時間枠：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. |
Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan
|
|
Association between Early mitral inflow velocity (E) as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.
時間枠：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. |
Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan
|
|
Association between Late mitral inflow velocity (A) as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.
時間枠：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. |
Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan
|
|
Association between E/A-ratio as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.
時間枠：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. |
Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan
|
|
Association between Deceleration time of early diastolic transmittal flow (dtE) as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.
時間枠：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. |
Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan
|
|
Association between Right ventricular diameter (RVD) as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.
時間枠：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. |
Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan
|
|
Association between left atrial volume (LAV) as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.
時間枠：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.
|
Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan
|
|
Association between 2D atrial global strain as determined during echocardiography and sleep apnea in patients with diabetic nephropathy.
時間枠：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.
|
Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan
|
協力者と研究者
スポンサー
捜査官
- スタディチェア：Niels H. Buus, MD PhD DMSc、Department of Renal diseases, Aarhus University Hospital
- 主任研究者：Sebastian Nielsen, MD student、Department of Renal diseases, Aarhus University Hospital
- スタディチェア：Jakob T. Nyvad, MD、The Clinic of Hypertension, Aarhus University Hospital
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- 1-10-72-122-20
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。
血管疾患の臨床試験
-
Cliniques universitaires Saint-Luc- Université...完了