Photobiomodulation for the Treatment of Diabetic Macular Edema

NCT02457975 | Completed Early Phase 1

• 1 other identifier: PRO00024065
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

The current application proposes to conduct a prospective, clinical trial in diabetic subjects with diabetic macular edema (DME) to evaluate the therapeutic efficacy of 670 nm photobiomodulation on validated clinical outcome measures and anatomical changes in central macula by optical coherence tomography (OCT) and other imaging modalities. A total of 30 diabetic patients with treatment-refractory clinically significant diabetic macular edema will be included in this study and randomized into two equal groups. One eye per participant will be included to avoid exposure of both eyes to the study intervention. If both eyes are eligible, the eye with worse visual acuity will become the study eye. One group will be treated with standard-of-care (intravitreal anti-VEGF agent) injections. The photobiomodulaton (PBM) intervention group will be treated with the standard-of-care intravitreal anti-VEGF (vascular endothelial growth factor) injections and 670 nm PBM in one eye. Baseline functional and anatomic assessments will be made and anti-VEGF therapy will be administered as determined by the treating Ophthalmologist.

Conditions

Diabetic Retinopathy

Keywords

Diabetic Macular Edema; Photobiomodulation; Phototherapy

Outcome Measures

Primary Outcomes (1)

• Visual Acuity as assessed by the Early Treatment of Diabetic Retinopathy Study (EDTRS) Classification

  Change from baseline at 8 weeks; Change from baseline at 24 weeks

Secondary Outcomes (1)

• Spectral Density-Optical Coherence Tomography (SD-OCT)

  Change from baseline at 8 weeks; Change from baseline at 24 weeks

Study Arms (2)

Intravitreous VEGF-inhibitors

ACTIVE COMPARATOR

Three intravitreous VEGF inhibitors - aflibercept (Eylea, Regeneron Pharmaceuticals), bevacizumab (Avastin, Genentech), and ranibizumab (Lucentis, Genentech) - are commonly used for the treatment of diabetic macular edema causing vision impairment and have been shown to be beneficial and relatively safe. Study participants in the anti-VEGF group will be treated with intravitreous injections of one of these agents: afibercept (2.0 mg), bevacizumab (1.25 mg) or ranibizumab (0.5 mg) at appropriate intervals as determined by the treating ophthalmologist.

Drug: intravitreous VEGF-inhibitors

670nm PBM plus VEGF-inhibitors

EXPERIMENTAL

Subjects in the 670 nm Photobiomodulation (PBM) intervention arm will be treated (in addition to Anti-VEGF treatment) with 670nm light (WARP10, Quantum, Devices, Inc, Barneveld, WI). The portable, battery-operated 670 nm LED array specifically designed not to generate heat will be held 1 inch from the closed treatment eye. A 90-sec light treatment will be delivered. After 90 sec a timer turns off the light. The dose of light delivered at the surface of the cornea is calculated to be 4.5 J/cm2 (90 sec x 0.05 W/cm2 = 4.5 J/cm2). PBM treatment will be applied for 90 sec once per day, three consecutive days per week for 8 weeks. Previous clinical studies, have shown this treatment regimen and dose to be safe and effective in the treatment of dry AMD and non-center involving DME

Device: 670nm PBM; Drug: intravitreous VEGF-inhibitors

Interventions

670nm PBM DEVICE

Battery operated, hand-held, 10 cm2 Light Emitting Diode (LED) array designed to deliver 50 mW/cm2 of light for 90 seconds resulting in a light dose of 4.5 Joules/cm2

Also known as: WARP10 by Quantum Devices, Inc (Barneveld, WI)

670nm PBM plus VEGF-inhibitors

intravitreous VEGF-inhibitors DRUG

Threeintravitreous VEGF inhibitors - aflibercept (Eylea, Regeneron Pharmaceuticals), bevacizumab (Avastin, Genentech), and ranibizumab (Lucentis, Genentech) - are commonly used for the treatment of diabetic macular edema causing vision impairment and have been shown to be beneficial and relatively safe. Study participants in the anti-VEGF group will be treated with intravitreous injections of one of these agents: afibercept (2.0 mg), bevacizumab (1.25 mg) or ranibizumab (0.5 mg) at appropriate intervals as determined by the treating ophthalmologist.

Also known as: aflibercept, bevacizumab, or ranibizumab

670nm PBM plus VEGF-inhibitors; Intravitreous VEGF-inhibitors

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients with type 1 or 2 diabetes

You may not qualify if:

• Uncontrolled glaucoma; aphasia cataract precluding fundus photography; external ocular infections; previous anti-VEGF or laser treatment in the preceding 3 months in both eyes; angiographic evidence of macular ischemia macular edema glycosylated hemoglobin of more than 11.0% past medical history of chronic renal failure an arteriothrombotic event within 6 months before randomization pregnancy or breastfeeding.

Sponsors & Collaborators

• Medical College of Wisconsin: lead
• University of Wisconsin, Milwaukee: collaborator

Study Sites (1)

Medical College of Wisconsin Froedert Hospital

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (9)

• Zhang X, Zeng H, Bao S, Wang N, Gillies MC. Diabetic macular edema: new concepts in patho-physiology and treatment. Cell Biosci. 2014 May 14;4:27. doi: 10.1186/2045-3701-4-27. eCollection 2014.

  PMID: 24955234 BACKGROUND

• Falavarjani KG, Nguyen QD. Adverse events and complications associated with intravitreal injection of anti-VEGF agents: a review of literature. Eye (Lond). 2013 Jul;27(7):787-94. doi: 10.1038/eye.2013.107. Epub 2013 May 31.

  PMID: 23722722 BACKGROUND

• Tang J, Herda AA, Kern TS. Photobiomodulation in the treatment of patients with non-center-involving diabetic macular oedema. Br J Ophthalmol. 2014 Aug;98(8):1013-5. doi: 10.1136/bjophthalmol-2013-304477. Epub 2014 Mar 28.

  PMID: 24682183 BACKGROUND

• Simo R, Sundstrom JM, Antonetti DA. Ocular Anti-VEGF therapy for diabetic retinopathy: the role of VEGF in the pathogenesis of diabetic retinopathy. Diabetes Care. 2014 Apr;37(4):893-9. doi: 10.2337/dc13-2002.

  PMID: 24652720 BACKGROUND

• Eells JT, Wong-Riley MT, VerHoeve J, Henry M, Buchman EV, Kane MP, Gould LJ, Das R, Jett M, Hodgson BD, Margolis D, Whelan HT. Mitochondrial signal transduction in accelerated wound and retinal healing by near-infrared light therapy. Mitochondrion. 2004 Sep;4(5-6):559-67. doi: 10.1016/j.mito.2004.07.033.

  PMID: 16120414 BACKGROUND

• Tang J, Du Y, Lee CA, Talahalli R, Eells JT, Kern TS. Low-intensity far-red light inhibits early lesions that contribute to diabetic retinopathy: in vivo and in vitro. Invest Ophthalmol Vis Sci. 2013 May 1;54(5):3681-90. doi: 10.1167/iovs.12-11018.

  PMID: 23557732 BACKGROUND

• Cheung N, Wong IY, Wong TY. Ocular anti-VEGF therapy for diabetic retinopathy: overview of clinical efficacy and evolving applications. Diabetes Care. 2014 Apr;37(4):900-5. doi: 10.2337/dc13-1990.

  PMID: 24652721 BACKGROUND

• Eells JT, Henry MM, Summerfelt P, Wong-Riley MT, Buchmann EV, Kane M, Whelan NT, Whelan HT. Therapeutic photobiomodulation for methanol-induced retinal toxicity. Proc Natl Acad Sci U S A. 2003 Mar 18;100(6):3439-44. doi: 10.1073/pnas.0534746100. Epub 2003 Mar 7.

  PMID: 12626762 BACKGROUND

• Chung H, Dai T, Sharma SK, Huang YY, Carroll JD, Hamblin MR. The nuts and bolts of low-level laser (light) therapy. Ann Biomed Eng. 2012 Feb;40(2):516-33. doi: 10.1007/s10439-011-0454-7. Epub 2011 Nov 2.

  PMID: 22045511 BACKGROUND

Related Links

• TORPA Study of Photobiomdulation for AMD

MeSH Terms

Conditions

Diabetic Retinopathy

Interventions

aflibercept; Bevacizumab; Ranibizumab

Condition Hierarchy (Ancestors)

Retinal Diseases; Eye Diseases; Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Judy Kim, MD

  MCW Dept of Ophthalmology

  PRINCIPAL INVESTIGATOR

• Sandeep Gopalakrishnan, Ph.D.

  UW-Milwaukee

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Ophthalmology

Study Record Dates

• First Submitted: May 25, 2015
• First Posted: May 29, 2015
• Study Start: June 1, 2015
• Primary Completion: August 30, 2019
• Study Completion: August 30, 2019
• Last Updated: September 10, 2019

Record last verified: 2019-09

Locations

US (1)