CPAP Effect on the Progression of Diabetic Retinopathy in Patients With Sleep Apnea

NCT ID: NCT02874313

Last Updated: 2021-05-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 82 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-08-31
• Study Completion Date: 2021-03-31

Brief Summary

Objectives: Main objective: To compare the percentage of patients with new microaneurysm or hard exudates after 12 months between the CPAP group and the control group. Secondary objectives: To compare the central macula volume, ganglion cell layer thickness and central fovea thickness at baseline and 12, 24 and 52 weeks after randomization between the two study groups; to compare the percentage of patients who have an improvement loss of visual acuity (more than or equal to 15 letters in patients with macular edema and more than or equal to five letters in patients without macular edema) among the baseline visit and the weeks 12, 24 and 52 between the two study groups; to compare the percentage of patients who reach a higher level of diabetic retinopathy at 54 weeks between the two study groups; to compare the resolution time of central macula thickness from the randomization between the two study groups; to compare the glycated hemoglobin at baseline and 12, 24 and 52 weeks after randomization between the two study groups; and to compare the serum levels of inflammatory cytokines, oxidative stress biomarkers, sympathetic tone, and intake regulator hormones at baseline and 12 and 52 weeks after randomization between the two study groups.

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 35 to 75 years with type 2 diabetes and a clinical diagnosis of mild diabetic retinopathy (with or without macular edema), better visual acuity from 20/40 to 20/320 letters and refraction with a spherical equivalent less than ± 5 diopter.

Efficacy variables: Thickness of the central sub-field, central subfield volume, ganglion cell layer thickness, and presence of clinical or subclinical macular edema, serous retinal or retinal pigment epithelium detachment, intraretinal cysts or haemorrhages assessed by optical coherence tomography; presence of cotton exudates, microhemorrhages, microaneurysms, , microvascular retinal abnormalities, or a vein/artery ratio > 2/1 in examination of ocular fundus/retinography; better corrected visual acuity; glycosylated hemoglobin (HbA1c); fasting glucose and insulin; homeostatic model assessment (HOMA) and QUICKI indices; lipid profile, troponin I, proBNP, homocysteine and C-reactive protein; systemic biomarkers of inflammation, oxidative stress, endothelial damage, sympathetic activity and appetite-regulating hormones and clinical questionnaires: short form (SF)-12, visual function questionnaire (VFQ25) and iPAQ.

Conditions

Diabetic Retinopathy; 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 oral antidiabetic drugs or insulin 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 oral antidiabetic drugs or insulin

Conventional anti-diabetic diet recommendations

Intervention Type: OTHER

Control treatment

Diet and conventional pharmacological treatment with oral antidiabetic drugs or insulin

Group Type: ACTIVE_COMPARATOR

Pharmacological treatment

Intervention Type: DRUG

Conventional pharmacological treatment with oral antidiabetic drugs or insulin

Conventional anti-diabetic diet recommendations

Intervention Type: OTHER

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 oral antidiabetic drugs or insulin

Intervention Type: DRUG

Conventional anti-diabetic diet recommendations

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Subjects aged 35 to 75 years old.
• 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 mild non-proliferative diabetic retinopathy, with or without macular edema.
• Best corrected visual acuity according to ETDRS optotype from 20/40 to 20/320 letters from 4 meters (score 73-25 letters) in the studied eye.
• Spherical equivalent refraction less than ± 5 dioptre.

Exclusion Criteria

• Prior systemic treatment for diabetic retinopathy, with the exception of nutritional supplements or vitamins.
• Pre-treatment with anti-vascular endothelial growth factor (VEGF) drugs in the studied eye. It is allowed a pre-treatment with anti-VEGF approved in the other eye more than 3 months ago.
• Prior systemic anti-VEGF, experimental or approved treatment, three months before the inclusion.
• Evidence of inflammation or infection in or around the studied eye.
• Treatment with troglitazone in the last three months.
• Eye surgery (including cataract surgery) in the studied eye three months before the inclusion.
• Late macular degeneration (geographical with foveal or neovascular involvement).
• Vascular retinal diseases, such as vascular occlusions.
• Previous diagnosis of other eye diseases that could lead to a decrease in visual acuity.
• 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: 35 Years
• Maximum Eligible Age: 75 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 Universitario La Paz

Madrid, , Spain

Countries

Spain

References

Garcia-Sanchez A, Villalain-Rodes I, Jaureguizar A, Zamarron E, Martinez-Ceron E, Casitas R, Galera R, Cubillos-Zapata C, Garcia J, Asencio M, Garcia-Rio F. Continuous Positive Airway Pressure Effect on Progression of Retinal Disease in Patients with Sleep Apnea and Nonproliferative Diabetic Retinopathy: A Randomized Clinical Trial. Ann Am Thorac Soc. 2024 Jan;21(1):102-113. doi: 10.1513/AnnalsATS.202304-296OC.

Reference Type: DERIVED

PMID: 37793101 (View on PubMed)

Other Identifiers

HULP PI-2476

Identifier Type: -

Identifier Source: org_study_id