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

NCT02816762 | Completed Phase 4

• 1 other identifier: HULP
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 6

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

Keywords

CPAP; Sleep apnea; Diabetes; Nephropathy; Albuminuria

Outcome Measures

Primary Outcomes (1)

• Change form baseline in albuminuria levels

  To compare the change in albuminuria levels between the patients allocated to CPAP group and the control group

  12 months

Secondary Outcomes (13)

• Change from baseline in glycated hemoglobin levels

  12 months

• Change form baseline in HOMA index

  12 months

• Change form baseline in QUICKI index

  12 months

• Change from baseline in cholesterol levels

  12 months

• Change from baseline in the levels of C-reactive protein

  12 months

Study Arms (2)

CPAP treatment

EXPERIMENTAL

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

Device: Continuous positive airway pressure; Drug: Pharmacological treatment; Other: Diet

Control treatment

ACTIVE COMPARATOR

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

Drug: Pharmacological treatment; Other: Diet

Interventions

Continuous positive airway pressure DEVICE

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

CPAP treatment

Pharmacological treatment DRUG

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

Also known as: Conventional pharmacological treatment

CPAP treatment; Control treatment

Diet OTHER

Conventional anti-diabetic diet recommendations

CPAP treatment; Control treatment

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hospital Universitario La Paz: lead

Study Sites (6)

Hospital Universitari Son Espases

Palma de Mallorca, Balearic Islands, 07120, Spain

Location

Hospital Universitario Infanta Sofía

San Sebastián de los Reyes, Madrid, 28703, Spain

Location

Hospital Universitario General de Guadalajara

Guadalajara, 19002, Spain

Location

Hosptial Universitario La Paz, IdiPAZ

Madrid, 28034, Spain

Location

Fundación Jiménez Díaz

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Related Publications (1)

• 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.

  PMID: 36342964 DERIVED

MeSH Terms

Conditions

Diabetic Nephropathies; Sleep Apnea Syndromes; Diabetes Mellitus; Kidney Diseases; Albuminuria

Interventions

Continuous Positive Airway Pressure; Drug Therapy; Diet

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Complications; Endocrine System Diseases; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Proteinuria; Urination Disorders; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Positive-Pressure Respiration; Respiration, Artificial; Airway Management; Therapeutics; Respiratory Therapy; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Officials

• Francisco Garcia-Rio, MD

  Hospital Universitario La Paz, IdiPAZ

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: May 31, 2016
• First Posted: June 29, 2016
• Study Start: June 1, 2016
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2020
• Last Updated: May 11, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

ES (6)