Is docosahexaenoic Acid (DHA) effective as treatment for patients with X-Linked Retinitis Pigmentosa?

X-linked retinitis pigmentosa is a severe inherited retinal degenerative disease with a frequency of 1 in 100,000 persons. Because no cure is available for this orphan disease and treatment options are limited, slowing of disease progression is considered to be a meaningful outcome.

A study was conducted in Dallas, Texas, at the Retina Foundation of the Southwest, and others, to determine whether high-dose docosahexaenoic acid (DHA), an ω-3 polyunsaturated fatty acid, slows progression of X-linked retinitis pigmentosa as measured by cone electroretinography (ERG).
 

This was a 4-year, single-site, randomized, placebo-controlled, double-masked phase 2 clinical trial that includes 78 male patients diagnosed as having X-linked retinitis pigmentosa. The subjects were randomized to either DHA or placebo. Final data did not include 2 patients with non–X-linked retinitis pigmentosa and 16 others who were unable to follow protocol during the first year. The remaining participants were tested annually and composed a modified intent-to-treat cohort (DHA group, n = 33; placebo group, n = 27). All participants received a multivitamin and were randomly assigned to oral DHA (30 mg/kg/d) or placebo.
 
The primary outcome measured was the rate of loss of cone ERG function, with rod and maximal ERG amplitudes and cone ERG implicit times as secondary outcomes. Capsule counts and red blood cell DHA levels were assessed to monitor adherence.
 
Average (6-month to 4-year) red blood cell DHA levels were 4-fold higher in the DHA group than in the placebo group (P < .001). There was no difference between the DHA and placebo groups in the rate of cone ERG functional loss (0.028 vs 0.022 log µV/y, respectively; P = .30). No group differences were evident for change in rod ERG (P = .27), maximal ERG (P = .65), or cone implicit time (no change over 4 years). The rate of cone loss (ie, event rate) was markedly reduced compared with rates in previous studies. No severe treatment-emergent adverse events were found.

The study concludes that long-term DHA supplementation did not demonstrate slowing the loss of cone or rod ERG function associated with X-linked retinitis pigmentosa. With participant dropout and lower-than-expected disease event rate limiting the power to detect statistical significance, the authors conclude that a larger sample size, longer trial, and attainment of a target blood DHA level (13%) would be desirable. They also caution that while DHA supplementation at 30 mg/kg/d does not present serious adverse effects, routine monitoring of gastrointestinal tolerance is prudent.

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