Leber's Hereditary Optic Neuropathy (LHON)
Conditions
Brief summary
The overall objective of the proposed research is to test the hypothesis that Near-infrared Light-emitting Diode (NIR-LED) therapy will stimulate mitochondrial function, attenuate oxidative stress, and improve cell survival and vision in subjects with Leber's Hereditary Optic Neuropathy (LHON).
Detailed description
To determine the effects of short term (3 month) near-infrared light NIR-LED therapy on anatomic and functional abnormalities of LHON as assessed by a wide variety of ophthalmologic tests, including visual acuity, optical coherence tomography, pattern electroretinography (pERG) N95 retinal ganglion cell peak, fERG-PhNR (flash ERG - Photopic Negative Response), and fundus photography.
Interventions
DEVICENear-infrared light-emitting diode (NIR-LED) therapy (Med Light 630 PRO (Medical Devices Inc.))
Subjects will be exposed to light emitted from a Med Light 630 PRO (Medical Devices Inc.) at a wavelength of 630 nm (+/-15nm) with an exposure of 4 J/cm2. This is accomplished by applying the 50 mW/cm2 LED-generated light to the closed study eye for 80 seconds. Treatments involve application of the LED-generated light for 80 seconds, twice daily.
Sponsors
Medical College of Wisconsin
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Sex - male and female. Men are affected with visual loss more frequently than women, with a male predominance of \ 85%. A minimum of 25% of men and 5% of women at risk for LHON experience visual loss. * Age - 18 years or older. The onset of visual loss typically occurs between the ages of 15 and 35 years, but otherwise classic LHON has been reported in many individuals both younger and older, with a range of age at onset from 2 to 80 years. * Diagnosis of LHON or a carrier of the gene mutation. Patient must be evaluated by molecular confirmation, with the 11778 and other mutations of Leber's Hereditary Optic Neuropathy stratified in later data analysis. * Able & willing to provide informed consent
Exclusion criteria
* Has an optic nerve disease other than LHON. * Significant renal disease, defined as a history of chronic renal failure requiring dialysis or kidney transplant. * Participation in an investigational trial within 30 days of NIR-LED treatment that involved treatment with any drug that has not received regulatory approval at the time of study entry. (Note: subjects cannot receive another investigational drug while participating in the study during the first 6 months.) * Major surgery within 28 days prior to participation or major surgery planned during the next 6 months. Major surgery is defined as a surgical procedure that is more extensive than fine needle biopsy/aspiration, placement of a central venous access device, removal/biopsy of a skin lesion, or placement of a peripheral venous catheter.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| N95 Peak Via pERG and fERG -PhNR | 12 months | The primary comparison will be a paired comparison of pre- and post-treatment retinal ganglion cell N95 pattern electroretinogram (pERG) peaks and fERG - Photopic Negative Response (PhNR). Pairing will be done between a subject's treatment and control eye. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Symptomatic LHON Patients. Study Arm 1) symptomatic LHON patients. Male and female LHON patients with treatable bilateral optic atrophy. Treat the worse of the 2 eyes if there is a measurable difference in subjective visual functions (visual acuity, peripheral vision).
Near-infrared light-emitting diode (NIR-LED) therapy (Med Light 630 PRO (Medical Devices Inc.)): Subjects will be exposed to light emitted from a Med Light 630 PRO (Medical Devices Inc.) at a wavelength of 630 nm (+/-15nm) with an exposure of 4 J/cm2. This is accomplished by applying the 50 mW/cm2 LED-generated light to the closed study eye for 80 seconds. Treatments involve application of the LED-generated light for 80 seconds, twice daily. | 4 |
| Asymptomatic LHON Mutation Carriers Study Arm 2) asymptomatic LHON mutation carriers. Can be male or female; have some dysfunction, with changes occurring over months. Patients in study arm 2 will not be exposed to NIR-LED, but only undergo diagnostic studies. | 0 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Symptomatic LHON Patients. | Total |
|---|---|---|
| Age, Categorical <=18 years | 0 participants | 0 participants |
| Age, Categorical >=65 years | 0 participants | 0 participants |
| Age, Categorical Between 18 and 65 years | 4 participants | 4 participants |
| Gender Female | 0 participants | 0 participants |
| Gender Male | 4 participants | 4 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 participants | 0 participants |
| Race (NIH/OMB) Asian | 0 participants | 0 participants |
| Race (NIH/OMB) Black or African American | 0 participants | 0 participants |
| Race (NIH/OMB) More than one race | 0 participants | 0 participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 participants | 0 participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 participants | 0 participants |
| Race (NIH/OMB) White | 4 participants | 4 participants |
| Region of Enrollment United States | 4 participants | 4 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 4 | 0 / 0 |
| serious Total, serious adverse events | 0 / 4 | 0 / 0 |
Outcome results
Primary
N95 Peak Via pERG and fERG -PhNR
The primary comparison will be a paired comparison of pre- and post-treatment retinal ganglion cell N95 pattern electroretinogram (pERG) peaks and fERG - Photopic Negative Response (PhNR). Pairing will be done between a subject's treatment and control eye.
Time frame: 12 months
Population: All participants were withdrawn before any data could be obtained.