Diabetic RetinopathyPhase 4RetinASNCT02874313
CPAP Effect on the Progression of Diabetic Retinopathy in Patients With Sleep Apnea
A Phase 4 study testing Continuous positive airway pressure, Pharmacological treatment and Conventional anti-diabetic diet recommendations in people with Diabetic Retinopathy and Sleep Apnea, run by Hospital Universitario La Paz at 1 site in Spain.
Trial 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… Read more about this study
- Who is it for?
- Ages 35 to 75 years
- Conditions the study is for
- Diabetic Retinopathy, Sleep Apnea
- What is being tested?
- Continuous positive airway pressure, Pharmacological treatment and Conventional anti-diabetic diet recommendations
- Type of treatment
- Pill or oral medicine, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 82 participants
- Where
- 1 siteSpain
- Study dates
- Aug 2016to Mar 2021
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 16Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Continuous Positive Airway Pressure on the Progression of Vascular Retinal Disease in Patients With Sleep Apnea and Non-proliferative Diabetic Retinopathy. A Randomized Clinical Trial
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.
Read more
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
- Being tested
- Continuous positive airway pressure, Pharmacological treatment, Conventional anti-diabetic diet recommendations
- Keywords
- CPAP, Sleep apnea, Diabetes, Diabetic retinopathy
- Medical subject headings
- Diabetic Retinopathy, Sleep Apnea Syndromes, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Continuous positive airway pressureDevice
Nocturnal continuous positive airway pressure by a nasal mask. CPAP pressure will be automatically titrated using a AutoSet device (ResMed).
Pharmacological treatmentDrug
Conventional pharmacological treatment with oral antidiabetic drugs or insulin
Conventional anti-diabetic diet recommendationsOther
| Study group | Role | What they receive |
|---|---|---|
| CPAP treatment | Experimental | Diet and conventional pharmacological treatment with oral antidiabetic drugs or insulin plus continuous positive airway pressure (CPAP) Receives: Device: Continuous positive airway pressure; Drug: Pharmacological treatment; Other: Conventional anti-diabetic diet recommendations |
| Control treatment | Active comparator | Diet and conventional pharmacological treatment with oral antidiabetic drugs or insulin Receives: Drug: Pharmacological treatment; Other: Conventional anti-diabetic diet recommendations |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in of retinal microaneurysm or hard exudates
To compare the change in percentage of retinal microaneurysm or hard exudates between the patients allocated to CPAP group and the control group
Measured: 12 months
Secondary outcomes (15)
Change from baseline of the central macula volume
To compare the change in central macula volume assessed by optical coherence tomography between the patients allocated to CPAP group and the control group
Measured: 3, 6 and 12 months
Change from baseline of the ganglion cell layer thickness
To compare the change in ganglion cell layer thickness assessed by optical coherence tomography between the patients allocated to CPAP group and the control group
Measured: 3, 6 and 12 months
Change from baseline of the central fovea thickness
To compare the change in the central fovea thickness assessed by optical coherence tomography between the patients allocated to CPAP group and the control group
Measured: 3, 6 and 12 months
Change from baseline of the severity level of diabetic retinopathy
To compare the change in the severity level of diabetic retinopathy between the patients allocated to CPAP group and the control group
Measured: 3, 6 and 12 months
Change from baseline of the visual acuity
To compare the change in the visual acuity between the patients allocated to CPAP group and the control group
Measured: 12 months
Change from baseline in glycated hemoglobin levels
To compare the change in glycated hemoglobin levels between the patients allocated to CPAP group and the control group
Measured: 3, 6 and 12 months
Change form baseline in HOMA index
To compare the change in HOMA index between the patients allocated to CPAP group and the control group
Measured: 3, 6 and 12 months
Change form baseline in QUICKI index
To compare the change in QUICKI index between the patients allocated to CPAP group and the control group
Measured: 3, 6 and 12 months
Change from baseline in the health-related quality of life assessed by the VFQ25 questionnaire
To compare the change in the total score and the domains of the questionnaire VFQ25 between the CPAP group and the control group
Measured: 12 months
Change from baseline in the health-related quality of life assessed by the SF-12 questionnaire
To compare the change in the total score and the domains of the questionnaire SF-12 between the CPAP group and the control group
Measured: 12 months
Change from baseline in the daily physical activity of patients with diabetic retinopathy and obstructive sleep apnea
To compare the change in the total score of the International Physical Activity Questionnaire (iPAQ) between the CPAP group and the control group
Measured: 12 months
Change form baseline in the plasmatic levels of biomarkers of inflammation
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
Measured: 12 months
Change form baseline in the plasmatic levels of appetite-regulating hormones
To compare the change in the plasmatic levels of leptin and adiponectin between the CPAP group and the control group
Measured: 12 months
Change form baseline in the plasmatic levels of endothelin
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
Measured: 12 months
Change from baseline of intraocular pressure
To compare the change in the intraocular pressure between the patients allocated to CPAP group and the control group
Measured: 3, 6 and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2016 (estimated)
- Study startAug 2016
- Primary completionMar 2021
- Study completionMar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetic RetinopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 82 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital Universitario La Paz
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Francisco Garcia-Rio, Hospital Universitario La Paz
- Investigators
- Francisco Garcia-Rio, MD, Study chair, Hospital Universitario La Paz, IdiPAZ
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02874313
- Sponsor's protocol ID
- HULP PI-2476
- Acronym
- RetinAS
- Status last verified
- May 2021
- First submitted
- 17 Aug 2016
- Last updated
- 11 May 2021
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 37793101
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Continuous Positive Airway Pressure on the Progression of Vascular Retinal Disease in Patients With Sleep Apnea and Non-proliferative Diabetic Retinopathy. A Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT02874313
- Acronym / sponsor ID
- RetinAS / HULP PI-2476
- Conditions
- Diabetic Retinopathy, Sleep Apnea
- Keywords
- CPAP, Sleep apnea, Diabetes, Diabetic retinopathy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 82 participants (actual)
- Lead sponsor
- Hospital Universitario La PazUniversity, hospital or other
- Study start
- Aug 2016
- Primary completion
- Mar 2021 (actual)
- Study completion
- Mar 2021 (actual)
- First posted
- 22 Aug 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CPAP treatment | Experimental | Device: Continuous positive airway pressure, Drug: Pharmacological treatment, Other: Conventional anti-diabetic diet recommendationsDiet and conventional pharmacological treatment with oral antidiabetic drugs or insulin plus continuous positive airway pressure (CPAP) |
| Control treatment | Active comparator | Drug: Pharmacological treatment, Other: Conventional anti-diabetic diet recommendationsDiet and conventional pharmacological treatment with oral antidiabetic drugs or insulin |
Who may qualify
- Ages
- 35 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Continuous positive airway pressureNocturnal continuous positive airway pressure by a nasal mask. CPAP pressure will be automatically titrated using a AutoSet device (ResMed). | Device | CPAP treatment |
| Pharmacological treatmentConventional pharmacological treatment with oral antidiabetic drugs or insulin | Drug | CPAP treatment, Control treatment |
| Conventional anti-diabetic diet recommendations | Other | CPAP treatment, Control treatment |
Primary outcome
Change from baseline in of retinal microaneurysm or hard exudates
Time frame: 12 months
To compare the change in percentage of retinal microaneurysm or hard exudates between the patients allocated to CPAP group and the control group
15 secondary outcomes
Change from baseline of the central macula volume
Time frame: 3, 6 and 12 months
Change from baseline of the ganglion cell layer thickness
Time frame: 3, 6 and 12 months
Change from baseline of the central fovea thickness
Time frame: 3, 6 and 12 months
Change from baseline of the severity level of diabetic retinopathy
Time frame: 3, 6 and 12 months
Change from baseline of the visual acuity
Time frame: 12 months
Change from baseline in glycated hemoglobin levels
Time frame: 3, 6 and 12 months
Change form baseline in HOMA index
Time frame: 3, 6 and 12 months
Change form baseline in QUICKI index
Time frame: 3, 6 and 12 months
Change from baseline in the health-related quality of life assessed by the VFQ25 questionnaire
Time frame: 12 months
Change from baseline in the health-related quality of life assessed by the SF-12 questionnaire
Time frame: 12 months
Change from baseline in the daily physical activity of patients with diabetic retinopathy and obstructive sleep apnea
Time frame: 12 months
Change form baseline in the plasmatic levels of biomarkers of inflammation
Time frame: 12 months
Change form baseline in the plasmatic levels of appetite-regulating hormones
Time frame: 12 months
Change form baseline in the plasmatic levels of endothelin
Time frame: 12 months
Change from baseline of intraocular pressure
Time frame: 3, 6 and 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2021.
- Derived from this study: PubMed 37793101Garcia-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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Francisco Garcia-Rio, MD study chair
Hospital Universitario La Paz, IdiPAZ
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Continuous positive airway pressure, Pharmacological treatment and Conventional anti-diabetic diet recommendations in people with Diabetic Retinopathy and Sleep Apnea, run by Hospital Universitario La Paz at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline in of retinal microaneurysm or hard exudates (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02874313, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 May 2021.