DHA and X-Linked Retinitis Pigmentosa

Study Overview
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Brief Summary
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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
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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).

Official Title
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Investigation of Effectiveness and Safety of High Dose Docosahexaenoic Acid (DHA) in X-Linked Retinitis Pigmentosa

Conditions
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Retinitis Pigmentosa, X-linked Genetic Diseases

Intervention / Treatment
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* Drug: docosahexaenoic acid OR corn/soy oil placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 7 Years
Maximum Age: 32 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1.<br>Oral Docosahexaenoic acid, dosage based on body weight | Drug: docosahexaenoic acid OR corn/soy oil placebo<br>* daily intake of DHA based on body weight or corn/soy oil placebo(oil not containing DHA; 4 year trial<br>* Other names: OR RANDOMIZED TO corn/soy oil placebo;|
| Placebo Comparator: 2<br>corn/soy oil placebo; oil not containing DHA...dosage based on body weight | Drug: docosahexaenoic acid OR corn/soy oil placebo<br>* daily intake of DHA based on body weight or corn/soy oil placebo(oil not containing DHA; 4 year trial<br>* Other names: OR RANDOMIZED TO corn/soy oil placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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retina, electroretinography, clinical trial, docosahexaenoic acid, omega-3 fatty acid, x-linked inheritance