CPAP Effect on Albuminuria in Patients With Diabetic Nephropathy and Obstructive Sleep Apnea

• Status: Completed
• Trial end date: 2020-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hospital Universitario La Paz
• Treatments: Angiotensin II; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Angiotensinogen; Enzyme Inhibitors

Criteria

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.