Protocol: A Pilot Study Evaluating Photobiomodulation Therapy for Diabetic Macular Edema
Status: Follow-up
Start Date: 04/09/2019
End Date:  
Clinical Trial ID: NCT03866473
Public Dataset:  

 

Full Protocol here 

Protocol Summary

Subject area

description

Title

A Pilot Study Evaluating Photobiomodulation Therapy for Diabetic Macular Edema (DME)

Précis

Randomized clinical trial evaluating the effect of photobiomodulation compared with sham on central subfield thickness (CST) in eyes with central-involved DME and good vision. 

Objectives

This study is being conducted to assess the effects of photobiomodulation on CST compared with sham in eyes with central-involved DME and good vision.  Photobiomodulation is irradiation by light in the far-red (FR) to near-infrared (NIR) region of the spectrum (630-900 nm).

 

Furthermore, this pilot study is being conducted to determine whether the conduct of a pivotal trial has merit based on an anatomic outcome and provide information on outcome measures needed to design a pivotal trial. 

Study Design

Randomized, multi-center, sham-controlled clinical trial.

 

There are two phases of the study; the primary outcome will be evaluated at the end of phase 1 (4 months).  At the 4-month visit, participants will switch to the alternative treatment.  The switch serves two purposes:

1) to provide participants originally assigned to sham the opportunity to receive the active treatment and

2) to explore the post-switch effects within treatment group.  No statistical comparisons will be performed in Phase 2 to compare treatment groups. 

 

Note: This is not a crossover design.

Number of Sites

Approximately 40

Endpoint

Primary Efficacy Outcome:

·         Mean change in CST from baseline at 4 months

Key Secondary Efficacy Outcomes:

Treatment Group Comparisons

·         Mean change in retinal volume from baseline at 4 months

·         Percentage of eyes with CST below OCT machine- and gender-specific threshold for DME at 4 months

·         Percentage of eyes receiving alternative treatment for DME by 4 months

·         Percentage of eyes with a ≥5 letter loss in visual acuity

·         Patient compliance

·         Exploratory assessment of treatment effect after the device is stopped or started (see section 7.10 for more details)

Population

Key Inclusion Criteria

·         Age >18 years

·         Type 1 or type 2 diabetes

      ·         At least one eye with each of the following:

·    Best corrected E-ETDRS visual acuity letter score ≥ 79 (i.e., 20/25 or better)

·    Ophthalmoscopic evidence of central-involved DME in study eye confirmed by CST on spectral domain OCT:

§  Zeiss Cirrus: ≥290 µm in women, and ≥305 µm in men

§ Heidelberg Spectralis: ≥305µm in women, and ≥320 µm in men

Key Exclusion Criteria               

·         No history of prior laser, surgical, intravitreous, or peribulbar treatment for DME or DR in the study eye within the prior 12 months

     o   If more than 12 months ago, no more              than 4 prior intraocular injections

o   Enrollment will be limited to a maximum of 15% of the planned sample size with any history of anti-VEGF treatment and a maximum of 15% with any history of PRP.

Sample Size

134

Treatment Groups

Random assignment (1:1) to photobiomodulation (PBM) or sham

Participant Duration

The trial will last up to 8 months for each participant (primary outcome at 4 months)

Protocol Overview

1.     Informed consent will be obtained.

2.   Study eligibility will be assessed.

3.   Prior to randomization, the participant’s willingness to proceed into the randomized trial will be confirmed.

4.   Eligible eyes (one per participant) will be randomly assigned to photobiomodulation or sham.  If a participant has two eligible eyes, the eye with the greatest CST will be selected as the study eye and the non-study eye will be followed to evaluate any potential contralateral effect.

5.  Training for at-home use will be performed with the randomized device on the day of randomization. 

6.   A follow-up phone call is performed at 1 week.

7.   Participants will return for a follow-up visit every month for the first 4 months and then every 2 months through 8 months.  The primary outcome assessment will be at 4 months.

8.  Following the primary outcome assessment, the participant will switch to the alternative treatment for the next 4 months. A summary of treatment procedures is included below.

 



Schedule of Study Visits and Procedures

 

 

Baseline

1-week Phone Call

Interim Visits

(1, 2, 3, 6M)

4 and 8 Month Outcome Visits

DME Tx Initiation Visit*

Device Training

X

 

 

 

 

Randomization

X

 

 

 

 

E-ETDRS Best Corrected Visual Acuity

X

 

X

X

X

Spectral Domain OCT§

X

 

X

X

X

OCTA?

X

 

 

X

 

Eye Exam

X

 

If Needed

X

X

Blood Pressure

X

 

 

 

 

HbA1c**

X

 

 

 

 

Compliance Assessment

 

X

X

X

 

Notes

Testing is only required for the study eye unless otherwise specified below.

*Alternative DME treatment (e.g. anti-VEGF) should not be performed unless protocol criteria are met.  If alternative DME treatment is planned at an unscheduled visit, study testing must be completed prior to treatment. 

Visual acuity performed on both eyes at each visit, including protocol refraction on both eyes at baseline, 4-month, and final visit, and on the study eye only at all other protocol visits.

Usual care vision may be used if eye has already been dilated when treatment is planned.

§OCT in both eyes at all visits; OCT may be obtained with Zeiss Cirrus or Heidelberg Spectralis OCT machines only.

?Baseline and 4-Month visit only at select sites with OCTA capabilities

Both eyes at baseline visit, study eye only at 4 month and 8 month visits.  Ocular exam at interim visits is at investigator discretion.  In general, an ocular exam should be completed if the OCT and/or visual acuity have worsened since baseline. 

**Does not need to be repeated if HbA1c available from within the prior 3 months; if not available, can be performed within 3 weeks after randomization.

Study Device

PBM Device

The advantages of LEDs are that they are compact, lightweight, and can be designed to produce many wavelengths and in an array of any shape.  The Warp 10 device used in prior human studies is a portable handheld device that emits red colored light of 670nm at a dose of 4.5 J/cm2 at 1 inch.  The device to be used in this study has been designed by PhotoOptx, LLC (Solon, OH) specifically for trial use.  It is worn as a single eye patch to maximize treatment effect.  The active treatment version will emit light of 670nm at a dose of 4.5 J/cm2 with an irradiance not greater than 50 mW/cm2.  The device includes a controller module to collect compliance data, which will be downloaded by site personnel at each visit.  The device includes an auto shut off after the desired treatment time. 

Sham Device

The sham device is identical, except that the light will be a blue-filtered white light at a low power.  The sham device is not expected to have any anatomic effect since the energy of the light in the far red to near-infrared/far red spectrum delivered by this device will be minimal and far below the thresholds used in previous preclinical and clinical studies to generate cellular or anatomic responses in the retina.

1.1 Outcome Measures Phase 1 (Baseline to 4 Months)

Primary Efficacy Endpoint(s): Mean change in CST from baseline

Secondary Efficacy Endpoint(s):

·         Mean change in retinal volume from baseline

·         Percentage of eyes with CST below OCT machine and gender-specific threshold for DME

·         Percentage of eyes receiving alternative treatment for DME*

·         Percentage of eyes with a 5-letter loss in visual acuity from baseline

·         Mean change in visual acuity from baseline*

·         Patient compliance*

*Outcomes marked with an asterisk will include descriptive statistics only and not statistical comparisons of treatment groups

 

 



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