Clinical trial NCT02816762: CPAP Effect on Albuminuria in Patients With Diabetic Nephropathy and Obstructive Sleep Apnea
Official title: Effect of Continuous Positive Airway Pressure on Albuminuria in Patients With Diabetic Nephropathy and Obstructive Sleep Apnea
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetic Nephropathy
Sleep Apnea
Keywords: CPAP
Sleep apnea
Diabetes
Nephropathy
Albuminuria
Lead sponsor: Hospital Universitario La Paz
Sponsor class: OTHER
First posted: 2016-06-29
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Change form baseline in albuminuria levels
timeFrame: 12 months
Secondary outcomes:
measure: Change from baseline in glycated hemoglobin levels
timeFrame: 12 months
measure: Change form baseline in HOMA index
timeFrame: 12 months
measure: Change form baseline in QUICKI index
timeFrame: 12 months
measure: Change from baseline in cholesterol levels
timeFrame: 12 months
measure: Change from baseline in the levels of C-reactive protein
timeFrame: 12 months
measure: Change from baseline in the health-related quality of life assessed by the SF-12 questionnaire
timeFrame: 12 months
measure: Change from baseline in the health-related quality of life assessed by the EuroQoL questionnaire
timeFrame: 12 months
measure: Change from baseline in the daily physical activity of patients with diabetic nephropathy and OSA
timeFrame: 12 months
measure: Change form baseline in the plasmatic levels of biomarkers of inflammation
timeFrame: 12 months
measure: Change form baseline in the plasmatic levels of 8-isoprostane
timeFrame: 12 months
measure: Change form baseline in the plasmatic levels of endothelin
timeFrame: 12 months
measure: Change form baseline in the plasmatic levels of appetite-regulating hormones
timeFrame: 12 months
measure: To identify the CPAP-responder subgroup of OSA patients with diabetic nephropathy
timeFrame: 12 months
Other outcomes:
Locations:
city: Palma de Mallorca
country: Spain
facility: Hospital Universitari Son Espases
state: Islas Baleares
city: San Sebastián de los Reyes
country: Spain
facility: Hospital Universitario Infanta Sofía
state: Madrid
city: Guadalajara
country: Spain
facility: Hospital Universitario General de Guadalajara
city: Madrid
country: Spain
facility: Hosptial Universitario La Paz, IdiPAZ
city: Madrid
country: Spain
facility: Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
Study officials:
affiliation: Hospital Universitario La Paz, IdiPAZ
name: Francisco Garcia-Rio, MD
role: STUDY_CHAIR
References:
citation: Zamarron E, Jaureguizar A, Garcia-Sanchez A, Diaz-Cambriles T, Alonso-Fernandez A, Lores V, Mediano O, Troncoso-Acevedo F, Cabello-Pelegrin S, Morales-Ruiz E, Ramirez-Prieto MT, Valiente-Diaz MI, Gomez-Garcia T, Casitas R, Martinez-Ceron E, Galera R, Cubillos-Zapata C, Garcia-Rio F. Continuous Positive Airway Pressure Effect on Albuminuria Progression in Patients with Obstructive Sleep Apnea and Diabetic Kidney Disease: A Randomized Clinical Trial. Am J Respir Crit Care Med. 2023 Mar 15;207(6):757-767. doi: 10.1164/rccm.202206-1091OC.