Diabetic Nephropathy, Sleep Apnea
Conditions
Keywords
CPAP, Sleep apnea, Diabetes, Nephropathy, Albuminuria
Brief summary
Objectives: Main objective: To assess the effect of 12 months of CPAP treatment added to conventional drug treatment on the albuminuria in patients with diabetic nephropathy and obstructive sleep apnea (OSA). Secondary objectives: To evaluate the effect of CPAP treatment on the estimated glomerular filtration rate of patients with diabetic nephropathy and OSA; determine the additional longterm CPAP effect on glycemic control, insulin resistance, lipid profile, health-related quality of life and biomarkers of cardiac function, inflammation, oxidative stress, sympathetic tone and appetite-regulating hormones in patients with diabetic nephropathy and OSA; and to identify the subgroup of patients with diabetic nephropathy and OSA in which 12 months of treatment with CPAP achieve a more pronounced reduction in albuminuria. Methodology: Randomized, multicenter, non-blinded, parallel groups, conventional treatment-controlled trial of 12 months of duration. Subjects will randomize to conventional dietary and pharmacological treatment or conventional dietary and pharmacological treatment plus continuous positive airway pressure (CPAP). Study subjects: Subjects 18 to 80 years with overweight or obesity and a clinical diagnosis of diabetic nephropathy, increased urinary albumin/creatinine ratio of 30 mg/g and an estimated glomerular filtration rate \>20 ml/min/1.73 m2, and treatment with stable doses of angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs) or anti-aldosterone drugs in the last four weeks. Efficacy variables: urinary albumin/creatinine ratio and estimated glomerular filtration rate; glycosylated hemoglobin (HbA1c); fasting glucose and insulin; homeostatic model assessment (HOMA) and QUICKI indices; total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides; Troponin I, proBNP, homocysteine and high-sensitivity C-reactive protein; systemic biomarkers (inflammation \[IL-6, IL-8 and tumor necrosis factor-α\], oxidative stress \[8-isoprostane\], endothelial damage \[endothelin, VCAM-1 and ICAM-1\], sympathetic activity \[neuropeptide Y\] and appetite-regulating hormones \[leptin and adiponectin\]) and clinical questionnaires: short form (SF)-12, EuroQoL and iPAQ.
Interventions
DEVICEContinuous positive airway pressure
Nocturnal continuous positive airway pressure by a nasal mask. CPAP pressure will be automatically titrated using a AutoSet device (ResMed).
Conventional pharmacological treatment with angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists or anti-aldosterone agents.
OTHERDiet
Conventional anti-diabetic diet recommendations
Sponsors
Hospital Universitario La Paz
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Subjects aged 18 to 80 years old * Overweight or obesity (BMI ≥25 kg/m2) * Previous diagnosis of type 2 diabetes, fulfilling at least one of the following criteria: 1) current treatment with oral antidiabetic drugs and/or insulin; 2) a fasting glucose value above 126 mg/dl on at least 2 occasions; 3) blood glucose level at 2 hours after an oral glucose tolerance test is equal to or more than 200 mg/dl; or 4) a glycated hemoglobin (HbA1c) level \> 6.5 % * Clinical diagnosis of diabetic nephropathy, with a urinary albumin/creatinine ratio \>30 mg/g and an estimated glomerular filtration rate more than 20 ml/min per 1.73 m2. * Treatment with stable doses of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers or anti-aldosterone agents in the last four weeks.
Exclusion criteria
* Non diabetic nephropathy (confirmed by biopsy). * Dialysis for acute renal failure within the 6 previous months. * Evidence in the clinic history of relevant bilateral stenosis of renal artery (\> 75%) * Urinary albumin/creatinine ratio higher than 3000 mg/g, at the baseline visit. * Systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 110 mm Hg at the baseline visit. * Stroke, transient ischemic attack, acute coronary syndrome, or hospitalization for heart failure worsening, within the previous 30 days. * Professional drivers, risk profession or respiratory failure. * Severe daytime sleepiness (Epworth sleepiness scale \>18) * Concomitant treatment with high doses of acetylsalicylic acid (\> 500 mg/day) or continuous treatment with non-steroidal anti-inflammatory drugs * Previous treatment with CPAP * Participation in another clinical trial within the 30 days prior to randomization.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change form baseline in albuminuria levels | 12 months | To compare the change in albuminuria levels between the patients allocated to CPAP group and the control group |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change form baseline in HOMA index | 12 months | To compare the change in HOMA index between the patients allocated to CPAP group and the control group |
| Change form baseline in QUICKI index | 12 months | To compare the change in QUICKI index between the patients allocated to CPAP group and the control group |
| Change from baseline in cholesterol levels | 12 months | To compare the change in the levels of total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides between the patients allocated to CPAP group and the control group |
| Change from baseline in the levels of C-reactive protein | 12 months | To compare the change in the levels of C-reactive protein between the patients allocated to CPAP group and the control group |
| Change from baseline in the health-related quality of life assessed by the SF-12 questionnaire | 12 months | To compare the change in the total score and the domains of the questionnaire SF-12 between the CPAP group and the control group |
| Change from baseline in the health-related quality of life assessed by the EuroQoL questionnaire | 12 months | To compare the change in the total score and the domains of the questionnaire EuroQoL between the CPAP group and the control group |
| Change from baseline in glycated hemoglobin levels | 12 months | To compare the change in glycated hemoglobin levels between the patients allocated to CPAP group and the control group |
| Change form baseline in the plasmatic levels of biomarkers of inflammation | 12 months | To compare the change in the plasmatic levels of interleukin (IL)-1beta, IL-6, IL-8 and tumor necrosis factor-alpha between the CPAP group and the control group |
| Change form baseline in the plasmatic levels of 8-isoprostane | 12 months | To compare the change in the plasmatic levels of 8-isoprostane between the CPAP group and the control group |
| Change form baseline in the plasmatic levels of endothelin | 12 months | To compare the change in the plasmatic levels of endothelin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) between the CPAP group and the control group |
| Change form baseline in the plasmatic levels of appetite-regulating hormones | 12 months | To compare the change in the plasmatic levels of leptin and adiponectin between the CPAP group and the control group |
| To identify the CPAP-responder subgroup of OSA patients with diabetic nephropathy | 12 months | To identify the subgroup of OSA patients with diabetic nephropathy in those the CPAP treatment achieve an albuminuria reduction \>20% from baseline. |
| Change from baseline in the daily physical activity of patients with diabetic nephropathy and OSA | 12 months | To compare the change in the total score of the International Physical Activity Questionnaire (iPAQ) between the CPAP group and the control group |
Countries
Spain
Outcome results
None listed