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

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ClinicalTrials.gov Identifier: NCT02816762
Recruitment Status : Recruiting
First Posted : June 29, 2016
Last Update Posted : October 4, 2016
Sponsor:
Information provided by (Responsible Party):
Francisco Garcia-Rio, Hospital Universitario La Paz

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 Type : Interventional  (Clinical Trial)
Estimated 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 : June 2016
Estimated Primary Completion Date : July 2019
Estimated Study Completion Date : September 2019

Resource links provided by the National Library of Medicine

U.S. FDA Resources

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 Name: 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 Name: Conventional pharmacological treatment
Other: Diet
Conventional anti-diabetic diet recommendations



Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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. 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

  13. 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.



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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02816762


Contacts
Contact: Francisco Garcia-Rio, MD +34639911718 fgr01m@gmail.com

Locations
Spain
Hospital Universitari Son Espases Recruiting
Palma de Mallorca, Islas Baleares, Spain, 07120
Contact: Alberto Alonso-Fernández         
Principal Investigator: Alberto Alonso-Fernández, MD         
Sub-Investigator: Sheila Cabello Pelegrín, MD         
Hospital Universitario Infanta Sofía Recruiting
San Sebastián de los Reyes, Madrid, Spain, 28703
Contact: Mayte Ramirez, MD         
Principal Investigator: Mayte Ramirez, MD         
Sub-Investigator: Vanesa Lores, MD         
Hospital Universitario General de Guadalajara Recruiting
Guadalajara, Spain, 19002
Contact: Olga Mediano, MD         
Principal Investigator: Olga Mediano, MD         
Sub-Investigator: Pilar Resano Barrio, MD         
Hosptial Universitario La Paz, IdiPAZ Recruiting
Madrid, Spain, 28034
Contact: Francisco Garcia-Rio, MD    +34639911718    fgr01m@gmail.com   
Sub-Investigator: Olga Costero, MD         
Sub-Investigator: Ester Zamarrón, MD         
Sub-Investigator: Elisabet Martínez-Cerón, MD         
Fundación Jiménez Díaz Recruiting
Madrid, Spain, 28040
Contact: Nicolas González Mangado         
Principal Investigator: Nicolás González-Mangado, MD         
Sub-Investigator: Paula Rodríguez Rodríguez, MD         
Hospital Universitario 12 de Octubre Recruiting
Madrid, Spain, 28041
Contact: Trinidad Diaz-Cambriles, MD         
Principal Investigator: Trinidad Diaz Cambriles, MD         
Sponsors and Collaborators
Hospital Universitario La Paz
Investigators
Study Chair: Francisco Garcia-Rio, MD Hospital Universitario La Paz, IdiPAZ

Responsible Party: Francisco Garcia-Rio, MD, Hospital Universitario La Paz
ClinicalTrials.gov Identifier: NCT02816762     History of Changes
Other Study ID Numbers: HULP
First Posted: June 29, 2016    Key Record Dates
Last Update Posted: October 4, 2016
Last Verified: October 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Francisco Garcia-Rio, Hospital Universitario La Paz:
CPAP
Sleep apnea
Diabetes
Nephropathy
Albuminuria

Additional relevant MeSH terms:
Diabetic Nephropathies
Apnea
Sleep Apnea Syndromes
Sleep Apnea, Obstructive
Kidney Diseases
Albuminuria
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Wake Disorders
Nervous System Diseases
Urologic Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Proteinuria
Urination Disorders
Urological Manifestations
Enzyme Inhibitors
Angiotensinogen
Angiotensin II
Angiotensin-Converting Enzyme Inhibitors
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Vasoconstrictor Agents
Serine Proteinase Inhibitors
Protease Inhibitors