Title

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

    Phase 2
  • Study Type

    Interventional
  • Intervention/Treatment

    efalex ...
  • Study Participants

    78
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
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).
Study Started
Sep 30
2004
Primary Completion
May 31
2012
Study Completion
Aug 31
2014
Results Posted
Mar 17
2015
Estimate
Last Update
Mar 17
2015
Estimate

Drug docosahexaenoic 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

  • Other names: DHA; omega-3 fatty acid, OR RANDOMIZED TO corn/soy oil placebo

1. Experimental

Oral Docosahexaenoic acid, dosage based on body weight

2 Placebo Comparator

corn/soy oil placebo; oil not containing DHA...dosage based on body weight

Criteria

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.

Summary

1. Docosahexaenoic Acid (DHA) Arm

Corn/Soy Oil Placebo Arm

All Events

Event Type Organ System Event Term 1. Docosahexaenoic Acid (DHA) Arm Corn/Soy Oil Placebo Arm

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.

DHA (Docosahexaenoic Acid)

0.028
log microvolts/year (Mean)
Standard Error: 0.001

Placebo (Corn/Soy Oil)

0.022
log microvolts/year (Mean)
Standard Error: 0.002

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.

DHA (Docosahexaenoic Acid)

0.01
change in amplitude, log microvolts/year (Mean)
Standard Error: 0.001

Placebo (Corn/Soy Oil)

0.023
change in amplitude, log microvolts/year (Mean)
Standard Error: 0.001

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.

DHA (Docosahexaenoic Acid) ARM

50.4
decibels (dB) (Mean)
Standard Error: 3.2

Placebo (Corn/Soy Oil) ARM

112.8
decibels (dB) (Mean)
Standard Error: 2.0

Total

78
Participants

Age, Customized

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Region of Enrollment

Sex/Gender, Customized

Overall Study

1. Docosahexaenoic Acid (DHA) Arm

Corn/Soy Oil Placebo Arm