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

May 10, 2021 updated by: Francisco Garcia-Rio, Hospital Universitario La Paz

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

180

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Guadalajara, Spain, 19002
        • Hospital Universitario General de Guadalajara
      • Madrid, Spain, 28040
        • Fundacion Jimenez Diaz
      • Madrid, Spain, 28041
        • Hospital Universitario 12 de Octubre
      • Madrid, Spain, 28034
        • Hosptial Universitario La Paz, IdiPAZ
    • Islas Baleares
      • Palma de Mallorca, Islas Baleares, Spain, 07120
        • Hospital Universitari Son Espases
    • Madrid
      • San Sebastián de los Reyes, Madrid, Spain, 28703
        • Hospital Universitario Infanta Sofía

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 78 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change form baseline in albuminuria levels
Time Frame: 12 months
To compare the change in albuminuria levels between the patients allocated to CPAP group and the control group
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline in glycated hemoglobin levels
Time Frame: 12 months
To compare the change in glycated hemoglobin levels between the patients allocated to CPAP group and the control group
12 months
Change form baseline in HOMA index
Time Frame: 12 months
To compare the change in HOMA index between the patients allocated to CPAP group and the control group
12 months
Change form baseline in QUICKI index
Time Frame: 12 months
To compare the change in QUICKI index between the patients allocated to CPAP group and the control group
12 months
Change from baseline in cholesterol levels
Time Frame: 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
12 months
Change from baseline in the levels of C-reactive protein
Time Frame: 12 months
To compare the change in the levels of C-reactive protein between the patients allocated to CPAP group and the control group
12 months
Change from baseline in the health-related quality of life assessed by the SF-12 questionnaire
Time Frame: 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
12 months
Change from baseline in the health-related quality of life assessed by the EuroQoL questionnaire
Time Frame: 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
12 months
Change from baseline in the daily physical activity of patients with diabetic nephropathy and OSA
Time Frame: 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
12 months
Change form baseline in the plasmatic levels of biomarkers of inflammation
Time Frame: 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
12 months
Change form baseline in the plasmatic levels of 8-isoprostane
Time Frame: 12 months
To compare the change in the plasmatic levels of 8-isoprostane between the CPAP group and the control group
12 months
Change form baseline in the plasmatic levels of endothelin
Time Frame: 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
12 months
Change form baseline in the plasmatic levels of appetite-regulating hormones
Time Frame: 12 months
To compare the change in the plasmatic levels of leptin and adiponectin between the CPAP group and the control group
12 months
To identify the CPAP-responder subgroup of OSA patients with diabetic nephropathy
Time Frame: 12 months
To identify the subgroup of OSA patients with diabetic nephropathy in those the CPAP treatment achieve an albuminuria reduction >20% from baseline.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospital Universitario La Paz

Investigators

  • Study Chair: Francisco Garcia-Rio, MD, Hospital Universitario La Paz, IdiPAZ

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2016

Primary Completion (Actual)

December 1, 2020

Study Completion (Actual)

December 1, 2020

Study Registration Dates

First Submitted

May 31, 2016

First Submitted That Met QC Criteria

June 24, 2016

First Posted (Estimate)

June 29, 2016

Study Record Updates

Last Update Posted (Actual)

May 11, 2021

Last Update Submitted That Met QC Criteria

May 10, 2021

Last Verified

May 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HULP

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Diabetic Nephropathy

Clinical Trials on Continuous positive airway pressure

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in New Zealand

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe