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

Sponsor

Hospital Universitario La Paz (Other)

Overall Status

Completed

CT.gov ID

NCT02816762

Collaborator

(none)

180

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetic Nephropathy Sleep Apnea	Device: Continuous positive airway pressure Drug: Pharmacological treatment Other: Diet	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

180 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Effect of Continuous Positive Airway Pressure on Albuminuria in Patients With Diabetic Nephropathy and Obstructive Sleep Apnea

Study Start Date :

Jun 1, 2016

Actual Primary Completion Date :

Dec 1, 2020

Actual Study Completion Date :

Dec 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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)	Device: Continuous positive airway pressure Nocturnal continuous positive airway pressure by a nasal mask. CPAP pressure will be automatically titrated using a AutoSet device (ResMed). Drug: Pharmacological treatment Conventional pharmacological treatment with angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists or anti-aldosterone agents. Other Names: Conventional pharmacological treatment Other: Diet Conventional anti-diabetic diet recommendations
Active Comparator: Control treatment Diet and conventional pharmacological treatment with angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists or anti-aldosterone agents.	Drug: Pharmacological treatment Conventional pharmacological treatment with angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists or anti-aldosterone agents. Other Names: Conventional pharmacological treatment Other: Diet Conventional anti-diabetic diet recommendations

Arm

Intervention/Treatment

Experimental: 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)

Device: Continuous positive airway pressure

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

Drug: Pharmacological treatment

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

Other Names:

Conventional pharmacological treatment

Other: Diet

Conventional anti-diabetic diet recommendations

Active Comparator: Control treatment

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

Drug: Pharmacological treatment

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

Other Names:

Conventional pharmacological treatment

Other: Diet

Conventional anti-diabetic diet recommendations

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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 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 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
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Universitari Son Espases	Palma de Mallorca	Islas Baleares	Spain	07120
2	Hospital Universitario Infanta Sofía	San Sebastián de los Reyes	Madrid	Spain	28703
3	Hospital Universitario General de Guadalajara	Guadalajara		Spain	19002
4	Hosptial Universitario La Paz, IdiPAZ	Madrid		Spain	28034
5	Fundación Jiménez Díaz	Madrid		Spain	28040
6	Hospital Universitario 12 de Octubre	Madrid		Spain	28041