Diabetic Macular Edema - Obstructive Sleep Apnea Relationship Study

NCT ID: NCT03597815

Last Updated: 2020-11-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

150 participants

Study Classification

OBSERVATIONAL

Study Start Date

2018-01-01

Study Completion Date

2020-12-01

Brief Summary

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The purpose of this study is to evaluate the relationship between DME and obstructive sleep apnea (OSA). OSA impacts millions of North Americans, many of whom are undiagnosed. The investigators aim to evaluate if a relationship exists between the two diseases, whether or not the severity of OSA impacts the severity of DME, and whether treating OSA results in better treatment outcomes for DME. The study will involve the standard of care provided for both DME (involving anti-VEGF injections) and OSA (involving continuous positive airway pressure \[CPAP\] machine).Approximately 150 subjects are expected to be enrolled in this study.

In summary:

Question 1: Is there a correlation between DME and OSA? Question 2: Is there a relationship between the severity of DME (CRT and vision) and OSA (AHI index)? Question 3: Does treating OSA result in improving DME metrics, and does it neutralize the outcomes at 1 year compared to OSA negatives.

Detailed Description

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A 12 month, non-randomized, controlled, prospective study evaluating the relationship between diabetic macular edema (DME) and obstructive sleep apnea (OSA).

Subjects eligible for the inclusion in the study will be grouped based on their diagnosis: DME \& OSA positive, DME positive only, OSA positive only, and DME \& OSA negative. All DME positive patients (irrespective of OSA status) will receive the standard of care treatment with anti-VEGF using Eylea in a standardized treat and extend protocol.

All patients will undergo baseline ophthalmologic examinations as part of a regular clinic visit including best-corrected visual acuity, intraocular pressure, slit lamp exam, dilated retinal exam, fluorescein angiography and optical coherence tomography (OCT). Diagnosis of diabetic macular edema will be confirmed with standard domain OCT. Diagnosis of OSA will be confirmed through gold standard of overnight polysomnography.

During each visit, the intraocular pressure and perfusion of the optic nerve head will be monitored for patient safety.

DME positive patients will receive a minimum of 6 injections with the first five occurring at 1-month intervals and the sixth occurring two months after the fifth. Further injections will be provided at the discretion of the ophthalmologist in according to the treat and extend protocol of Eylea. Data for Visits 1 and 4 in Table 1 will be collected at the first and sixth injections whereas the other injection visits will be treated as regular office visits and not study visits.

The investigators aim to identify the presence of OSA using the gold standard testing of an overnight sleep study to determine the prevalence of OSA in the DME population. Further, the investigators will attempt to determine if there is a correlation of OSA by comparing it to non-DME patients who have NPDR.

The mechanism of OSA action on diabetic microvascular complications may involve increased inflammatory responses and oxidative stress pathways such as increased advanced glycation end products. By comparing the gold standard metric of severity index of OSA (Apnea-hypopnea index) to DME metrics (LogMAR Snellen vision and CRT) at the baseline of both disease diagnoses, the investigators can determine severity association.

The specific metrics of DME treatment (Vision, CRT, number of injections) will be compared to pre-CPAP data to determine what the impact of CPAP was (if any) on DME treatment metrics. Further, the investigators aim to compare the one-year post-CPAP DME treatment metrics against one-year non-CPAP/non-OSA patients to determine the relative impact against a control group.

Conditions

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Diabetic Macular Edema Sleep Apnea Non Proliferative Diabetic Retinopathy

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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DME positive, OSA positive

Visit 1: Baseline DME Treatment. Includes first EYELEA(aflibercept) injection. (DME positive patients will receive a minimum of 6 injections with the first five occurring at 1-month intervals and the sixth occurring two months after the fifth. Further injections will be provided at the discretion of the ophthalmologist in according to the treat and extend protocol of Eylea to ensure the DME is resolved by the end of the study.) Each injection is 2 mg (0.05 mL). Visit 2: Diagnosis of OSA - Overnight sleep study Visit 3: 1 month follow up post-CPAP initiation Visit 4: 6-month visit post DME initial treatment Visit 5: 2-3 month follow up - titration study (at sleep lab) Visit 6: 12-month visit post DME initial treatment in the OSA- group and at least 3 months post CPAP initiation in the OSA+ group Visit 7: 12-month sleep apnea follow up

Aflibercept 40 MG/ML [Eylea]

Intervention Type DRUG

Intravitreal injection, form of anti-VEGF therapy

OSA diagnostic test - overnight sleep study

Intervention Type DIAGNOSTIC_TEST

Overnight with specialist care in hospital - heart, lung and brain activity monitored.

CPAP therapy for OSA positive patients

Intervention Type DEVICE

positive airway pressure ventilator, applies mild air pressure in a continuous basis to keep the airways continuously open in patients who are able to breath spontaneously on their own.

DME positive, OSA negative

Visit 1: Baseline DME Treatment Includes first EYELEA(aflibercept) injection. (DME positive patients will receive a minimum of 6 injections with the first five occurring at 1-month intervals and the sixth occurring two months after the fifth. Further injections will be provided at the discretion of the ophthalmologist in according to the treat and extend protocol of Eylea to ensure the DME is resolved by the end of the study.) Each injections is 2 mg (0.05 mL). Visit 2: Diagnosis of OSA - Overnight sleep study Visit 3: 6-month visit post DME initial treatment Visit 4: 12-month visit post DME initial treatment in the OSA- group and at least 3 months post CPAP initiation in the OSA+ group

Aflibercept 40 MG/ML [Eylea]

Intervention Type DRUG

Intravitreal injection, form of anti-VEGF therapy

OSA diagnostic test - overnight sleep study

Intervention Type DIAGNOSTIC_TEST

Overnight with specialist care in hospital - heart, lung and brain activity monitored.

DME negative (NPDR positive), OSA positive

no injections needed. Visit 1: Baseline NPDR diagnosis Sleep lab visits Visit 2: Diagnosis of OSA - Overnight sleep study Visit 3: 1 month follow up post-CPAP initiation Visit 4: 2-3 month follow up - titration study Visit 5: 12-month sleep apnea follow up

OSA diagnostic test - overnight sleep study

Intervention Type DIAGNOSTIC_TEST

Overnight with specialist care in hospital - heart, lung and brain activity monitored.

CPAP therapy for OSA positive patients

Intervention Type DEVICE

positive airway pressure ventilator, applies mild air pressure in a continuous basis to keep the airways continuously open in patients who are able to breath spontaneously on their own.

DME negative (NPDR positive), OSA negative

no injections needed. Visit 1: Baseline NPDR diagnosis Visit 2: Diagnosis of OSA - Overnight sleep study

OSA diagnostic test - overnight sleep study

Intervention Type DIAGNOSTIC_TEST

Overnight with specialist care in hospital - heart, lung and brain activity monitored.

Interventions

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Aflibercept 40 MG/ML [Eylea]

Intravitreal injection, form of anti-VEGF therapy

Intervention Type DRUG

OSA diagnostic test - overnight sleep study

Overnight with specialist care in hospital - heart, lung and brain activity monitored.

Intervention Type DIAGNOSTIC_TEST

CPAP therapy for OSA positive patients

positive airway pressure ventilator, applies mild air pressure in a continuous basis to keep the airways continuously open in patients who are able to breath spontaneously on their own.

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

* 18 years of age or greater
* Ability to understand and provide written consent
* Type II diabetes patients and evidence of Diabetic Retinopathy
* Patients with and without DME
* Able and willing to comply with all treatment and follow-up procedures

Exclusion Criteria

* Contraindications to Eylea including: stroke within the past month, ocular or periocular infection, active intraocular inflammation, hypersensitivity to Eylea and/or its excipients.
* Contraindication to CPAP including: severe bullous lung disease, pneumothorax, pathologically low blood pressure, dehydration, cerebrospinal fluid leak, recent cranial surgery, or trauma
* Any other types of retinal diseases such as retinal detachment
* Any other types of macular disease such as age-related macular degeneration
* Mental capacity to comply is impaired (i.e. dementia)
* Pregnant or breastfeeding women
* Participation in any drug or device clinical investigation within 30 days prior to entry into the study
Minimum Eligible Age

18 Years

Maximum Eligible Age

110 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Uptown Eye Specialists

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Sohel Somani

Role: PRINCIPAL_INVESTIGATOR

Uptown Eye

Locations

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Uptown Eye Speicialists

Brampton, Otario, Canada

Site Status

Countries

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Canada

References

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Foster GD, Sanders MH, Millman R, Zammit G, Borradaile KE, Newman AB, Wadden TA, Kelley D, Wing RR, Sunyer FX, Darcey V, Kuna ST; Sleep AHEAD Research Group. Obstructive sleep apnea among obese patients with type 2 diabetes. Diabetes Care. 2009 Jun;32(6):1017-9. doi: 10.2337/dc08-1776. Epub 2009 Mar 11.

Reference Type BACKGROUND
PMID: 19279303 (View on PubMed)

Resnick HE, Redline S, Shahar E, Gilpin A, Newman A, Walter R, Ewy GA, Howard BV, Punjabi NM; Sleep Heart Health Study. Diabetes and sleep disturbances: findings from the Sleep Heart Health Study. Diabetes Care. 2003 Mar;26(3):702-9. doi: 10.2337/diacare.26.3.702.

Reference Type BACKGROUND
PMID: 12610025 (View on PubMed)

Sacramento JF, Ribeiro MJ, Rodrigues T, Guarino MP, Diogo LN, Seica R, Monteiro EC, Matafome P, Conde SV. Insulin resistance is associated with tissue-specific regulation of HIF-1alpha and HIF-2alpha during mild chronic intermittent hypoxia. Respir Physiol Neurobiol. 2016 Jul;228:30-8. doi: 10.1016/j.resp.2016.03.007. Epub 2016 Mar 15.

Reference Type BACKGROUND
PMID: 26993367 (View on PubMed)

Reichmuth KJ, Austin D, Skatrud JB, Young T. Association of sleep apnea and type II diabetes: a population-based study. Am J Respir Crit Care Med. 2005 Dec 15;172(12):1590-5. doi: 10.1164/rccm.200504-637OC. Epub 2005 Sep 28.

Reference Type BACKGROUND
PMID: 16192452 (View on PubMed)

Shiba T, Sato Y, Takahashi M. Relationship between diabetic retinopathy and sleep-disordered breathing. Am J Ophthalmol. 2009 Jun;147(6):1017-21. doi: 10.1016/j.ajo.2008.12.027. Epub 2009 Mar 9.

Reference Type BACKGROUND
PMID: 19268888 (View on PubMed)

West SD, Groves DC, Lipinski HJ, Nicoll DJ, Mason RH, Scanlon PH, Stradling JR. The prevalence of retinopathy in men with Type 2 diabetes and obstructive sleep apnoea. Diabet Med. 2010 Apr;27(4):423-30. doi: 10.1111/j.1464-5491.2010.02962.x.

Reference Type BACKGROUND
PMID: 20536514 (View on PubMed)

Banerjee D, Leong WB, Arora T, Nolen M, Punamiya V, Grunstein R, Taheri S. The potential association between obstructive sleep apnea and diabetic retinopathy in severe obesity-the role of hypoxemia. PLoS One. 2013 Nov 18;8(11):e79521. doi: 10.1371/journal.pone.0079521. eCollection 2013.

Reference Type BACKGROUND
PMID: 24260240 (View on PubMed)

Leong WB, Jadhakhan F, Taheri S, Chen YF, Adab P, Thomas GN. Effect of obstructive sleep apnoea on diabetic retinopathy and maculopathy: a systematic review and meta-analysis. Diabet Med. 2016 Feb;33(2):158-68. doi: 10.1111/dme.12817. Epub 2015 Jul 4.

Reference Type BACKGROUND
PMID: 26031931 (View on PubMed)

Mason RH, West SD, Kiire CA, Groves DC, Lipinski HJ, Jaycock A, Chong VN, Stradling JR. High prevalence of sleep disordered breathing in patients with diabetic macular edema. Retina. 2012 Oct;32(9):1791-8. doi: 10.1097/IAE.0b013e318259568b.

Reference Type BACKGROUND
PMID: 22714043 (View on PubMed)

Mason RH, Kiire CA, Groves DC, Lipinski HJ, Jaycock A, Winter BC, Smith L, Bolton A, Rahman NM, Swaminathan R, Chong VN, Stradling JR. Visual improvement following continuous positive airway pressure therapy in diabetic subjects with clinically significant macular oedema and obstructive sleep apnoea: proof of principle study. Respiration. 2012;84(4):275-82. doi: 10.1159/000334090. Epub 2011 Dec 20.

Reference Type BACKGROUND
PMID: 22189259 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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DME-OSA

Identifier Type: -

Identifier Source: org_study_id