Diabetic Macular Edema - Obstructive Sleep Apnea Relationship Study

NCT03597815 | Unknown

• 1 other identifier: DME-OSA
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Diabetic Macular Edema; Sleep Apnea; Non Proliferative Diabetic Retinopathy

Outcome Measures

Primary Outcomes (4)

• Presence of DME

  First visit, 0 months

• Presence of OSA

  First visit, 0 months

• Snellen visual acuity

  12 months

• Apnea-Hypopnea Index

  12 months

Secondary Outcomes (3)

• Central Retinal Thickness

  12 months

• Number of injections

  7 months +

• CPAP compliance

  12 months

Study Arms (4)

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

Drug: Aflibercept 40 MG/ML [Eylea]; Diagnostic Test: OSA diagnostic test - overnight sleep study; Device: CPAP therapy for OSA positive patients

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

Drug: Aflibercept 40 MG/ML [Eylea]; Diagnostic Test: OSA diagnostic test - overnight sleep study

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

Diagnostic Test: OSA diagnostic test - overnight sleep study; Device: CPAP therapy for OSA positive patients

DME negative (NPDR positive), OSA negative

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

Diagnostic Test: OSA diagnostic test - overnight sleep study

Interventions

Aflibercept 40 MG/ML [Eylea] DRUG

Intravitreal injection, form of anti-VEGF therapy

DME positive, OSA negative; DME positive, OSA positive

OSA diagnostic test - overnight sleep study DIAGNOSTIC_TEST

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

DME negative (NPDR positive), OSA negative; DME negative (NPDR positive), OSA positive; DME positive, OSA negative; DME positive, OSA positive

CPAP therapy for OSA positive patients 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 positive; DME positive, OSA positive

Eligibility Criteria

• Age: 18 Years - 110 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients at Uptown Eye Clinic who comply with the inclusion and exclusion criteria.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Uptown Eye Specialists: lead

Study Sites (1)

Uptown Eye Speicialists

Brampton, Otario, L6Y0P6, Canada

Location

Related Publications (10)

• 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.

  PMID: 19279303 BACKGROUND

• 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.

  PMID: 12610025 BACKGROUND

• 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.

  PMID: 26993367 BACKGROUND

• 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.

  PMID: 16192452 BACKGROUND

• 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.

  PMID: 19268888 BACKGROUND

• 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.

  PMID: 20536514 BACKGROUND

• 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.

  PMID: 24260240 BACKGROUND

• 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.

  PMID: 26031931 BACKGROUND

• 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.

  PMID: 22714043 BACKGROUND

• 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.

  PMID: 22189259 BACKGROUND

MeSH Terms

Conditions

Sleep Apnea Syndromes

Interventions

aflibercept

Condition Hierarchy (Ancestors)

Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Study Officials

• Sohel Somani

  Uptown Eye

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 3, 2018
• First Posted: July 24, 2018
• Study Start: January 1, 2018
• Primary Completion: March 31, 2020
• Study Completion: December 1, 2020
• Last Updated: November 24, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)