Retinitis Pigmentosa, X-linked Genetic Diseases
Conditions
Keywords
retina, electroretinography, clinical trial, docosahexaenoic acid, omega-3 fatty acid, x-linked inheritance
Brief summary
Purpose: Retinitis pigmentosa (RP) is characterized by progressive loss of visual function due to specific genetic mutations. This trial is focused on patients with one of the most severe forms of the disease, X-linked inherited RP (XLRP). This disease is characterized by early onset (typically loss of night vision as a child) followed by loss of peripheral vision as a teenager and young adult. There is no male-to-male transmission of the disease in the family. There is no cure for RP and treatment options are limited. Two clinical trials have not found a benefit from nutritional supplementation with the long-chain polyunsaturated fatty acid, docosahexaenoic acid (DHA), at low daily doses although there is evidence that it slows disease progression in certain instances. In this clinical trial, we propose that a high dose nutritional DHA supplement will slow the loss of visual function and preserve usable vision in patients with XLRP. This study is a 4-year placebo-controlled randomized clinical trial meaning that patients have a 50-50 chance of receiving placebo or experimental treatment. A total of 66 patients will be enrolled; 33 will receive placebo and 33 will receive the treatment. Entry criteria include diagnosis of XLRP by an ophthalmologist, age 7 to 32 years, male, sufficient visual function such that disease progression can be followed for the entire duration of the trial, and a willingness to visit the testing site (Dallas, TX) once a year. Annual visual function testing includes ETDRS visual acuity, full-field and multifocal electroretinography (ERG), static peripheral visual fields, and fundus photography. Cone ERG function is the primary outcome measure. Funding Source - FDA, Foundation Fighting Blindness, DSM Nutritionals
Detailed description
Location & Contact Information: Retina Foundation of the Southwest, 9600 N. Central Expressway, Suite 200, Dallas, TX 75231 Contact: Dr. D. Hoffman (dhoffman@retinafoundation.org) or Dr. D. Birch (dbirch@retinafoundation.org).
Interventions
DRUGdocosahexaenoic acid OR corn/soy oil placebo
daily intake of DHA based on body weight or corn/soy oil placebo(oil not containing DHA; 4 year trial
Sponsors
Foundation Fighting Blindness
DSM Nutritional Products, Inc.
Retina Foundation of the Southwest
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
7 Years to 32 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of RP by a retinal specialist * Clinical diagnosis consistent with X-linked inheritance * Enrolling minors and young adults (early onset of X-linked disease; ages 7 to 32) * Measurable cone ERG responses --patients with less than 0.64 microvolt response to 31-Hz flicker will be excluded as they are more likely to become undetectable during the study * Both eyes must meet entry criteria as both will be tested (i.e., no cataracts requiring surgery or retinal detachments). * Media clarity sufficient for fundus photography * Able to return to study site at yearly intervals * Willing to supply blood samples at 6-month intervals * Judiciously take the placebo or DHA supplement for the 4-year study duration * Patient/parent/guardian understands and signs consent form.
Exclusion criteria
* Excessive fish consumption (e.g., cold water fish such as salmon, tuna, sardines) and/or fish oil supplementation (or other oil containing DHA) * Baseline RBC-DHA levels showing evidence of supplementation (a typical level of RBC-DHA in normals is about 3.8%) * Chronic metabolic disease that may interfere with fatty acid metabolism or require anti-coagulant medication No ethnic or racial groups will be excluded.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of LOSS of 31 Hertz Cone Electroretinographic Function | 4 years | Hypothesis #1: Elevation of red blood cell-docosahexaenoic acid levels will slow the progressive loss of 31 hertz cone electroretinographic response in this 4-year trial. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of LOSS of Rod Electroretinographic Function | 4 years | Hypothesis #1: Elevation of red blood cell-docosahexaenoic acid levels will slow the progressive loss of rod electroretinographic response in this 4-year trial. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Loss of Peripheral Visual Fields | 4 years | Hypothesis: Elevation of red blood cell-docosahexaenoic acid levels will slow the progressive loss of peripheral visual fields in this 4-year trial. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 1. Docosahexaenoic Acid (DHA) Arm Docosahexaenoic acid (an omega-3 polyunsaturated fatty acid) taken orally at a dosage of 30 mg/kg body weight/day for a 4-year duration trial. | 41 |
| Corn/Soy Oil Placebo Arm Corn/soy oil placebo (oils not containing DHA); dosage based on body weight for 4-year trial | 37 |
| Total | 78 |
Baseline characteristics
| Characteristic | Total | 1. Docosahexaenoic Acid (DHA) Arm | Corn/Soy Oil Placebo Arm |
|---|---|---|---|
| Age, Customized Age | 16.7 years STANDARD_DEVIATION 7.1 | 16.7 years STANDARD_DEVIATION 7.8 | 16.2 years STANDARD_DEVIATION 6.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 4 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 73 Participants | 37 Participants | 36 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 7 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 70 Participants | 37 Participants | 33 Participants |
| Region of Enrollment Canada | 5 participants | 3 participants | 2 participants |
| Region of Enrollment United States | 73 participants | 38 participants | 35 participants |
| Sex/Gender, Customized male | 78 participants | 41 participants | 37 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 9 / 33 | 16 / 27 |
| serious Total, serious adverse events | 0 / 33 | 0 / 27 |
Outcome results
Primary
Rate of LOSS of 31 Hertz Cone Electroretinographic Function
Hypothesis #1: Elevation of red blood cell-docosahexaenoic acid levels will slow the progressive loss of 31 hertz cone electroretinographic response in this 4-year trial.
Time frame: 4 years
Population: Number of participants completing at least one year of trial (i.e., modified intent to treat cohort)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DHA (Docosahexaenoic Acid) | Rate of LOSS of 31 Hertz Cone Electroretinographic Function | 0.028 log microvolts/year | Standard Error 0.001 |
| Placebo (Corn/Soy Oil) | Rate of LOSS of 31 Hertz Cone Electroretinographic Function | 0.022 log microvolts/year | Standard Error 0.002 |
p-value: 0.3Mixed Models Analysis
Secondary
Rate of LOSS of Rod Electroretinographic Function
Hypothesis #1: Elevation of red blood cell-docosahexaenoic acid levels will slow the progressive loss of rod electroretinographic response in this 4-year trial.
Time frame: 4 years
Population: Number of participants completing at least one year of trial (i.e., modified intent to treat cohort)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DHA (Docosahexaenoic Acid) | Rate of LOSS of Rod Electroretinographic Function | 0.010 change in amplitude, log microvolts/year | Standard Error 0.001 |
| Placebo (Corn/Soy Oil) | Rate of LOSS of Rod Electroretinographic Function | 0.023 change in amplitude, log microvolts/year | Standard Error 0.001 |
p-value: 0.27Mixed Models Analysis
p-value: 0.27Mixed Models Analysis
Other Pre-specified
Loss of Peripheral Visual Fields
Hypothesis: Elevation of red blood cell-docosahexaenoic acid levels will slow the progressive loss of peripheral visual fields in this 4-year trial.
Time frame: 4 years
Population: Only participants completing at least one year of trial
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DHA (Docosahexaenoic Acid) | Loss of Peripheral Visual Fields | 50.4 decibels (dB) | Standard Error 3.2 |
| Placebo (Corn/Soy Oil) | Loss of Peripheral Visual Fields | 112.8 decibels (dB) | Standard Error 2 |
p-value: 0.000008Mixed Models Analysis