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

NCT ID: NCT02816762

Last Updated: 2021-05-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 180 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-30
• Study Completion Date: 2020-12-31

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.

Conditions

Diabetic Nephropathy; Sleep Apnea

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CPAP treatment

Diet and conventional pharmacological treatment with angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists or anti-aldosterone agents plus continuous positive airway pressure (CPAP)

Group Type: EXPERIMENTAL

Continuous positive airway pressure

Intervention Type: DEVICE

Nocturnal continuous positive airway pressure by a nasal mask. CPAP pressure will be automatically titrated using a AutoSet device (ResMed).

Pharmacological treatment

Intervention Type: DRUG

Conventional pharmacological treatment with angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists or anti-aldosterone agents.

Diet

Intervention Type: OTHER

Conventional anti-diabetic diet recommendations

Control treatment

Diet and conventional pharmacological treatment with angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists or anti-aldosterone agents.

Group Type: ACTIVE_COMPARATOR

Pharmacological treatment

Intervention Type: DRUG

Conventional pharmacological treatment with angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists or anti-aldosterone agents.

Diet

Intervention Type: OTHER

Conventional anti-diabetic diet recommendations

Interventions

Continuous positive airway pressure

Nocturnal continuous positive airway pressure by a nasal mask. CPAP pressure will be automatically titrated using a AutoSet device (ResMed).

Intervention Type: DEVICE

Pharmacological treatment

Conventional pharmacological treatment with angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists or anti-aldosterone agents.

Intervention Type: DRUG

Diet

Conventional anti-diabetic diet recommendations

Intervention Type: OTHER

Other Intervention Names

Conventional pharmacological treatment

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospital Universitario La Paz

OTHER

Sponsor Role: lead

Responsible Party

Francisco Garcia-Rio

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Francisco Garcia-Rio, MD

Role: STUDY_CHAIR

Hospital Universitario La Paz, IdiPAZ

Locations

Hospital Universitari Son Espases

Palma de Mallorca, Balearic Islands, Spain

Hospital Universitario Infanta Sofía

San Sebastián de los Reyes, Madrid, Spain

Hospital Universitario General de Guadalajara

Guadalajara, , Spain

Hosptial Universitario La Paz, IdiPAZ

Madrid, , Spain

Fundación Jiménez Díaz

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Countries

Spain

References

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.

Reference Type: DERIVED

PMID: 36342964 (View on PubMed)

Other Identifiers

HULP

Identifier Type: -

Identifier Source: org_study_id