Investigating the Effect of Vitamin A Supplementation on Retinitis Pigmentosa

Retinitis pigmentosa (RP) is a collective term for a group of inherited retinal dystrophies
that are a major cause of irreversible blindness. RP of some type occurs in approximately 1
out of 3500 persons in the United States. Gene mutations are responsible for the majority of
RP. To date, mutations have been identified in 30 different genes linked to RP. The visual
prognosis of RP is poor, since the gradual but relentless visual field loss leads eventually
to some degree of blindness. Although no effective treatment for RP has been identified,
participants supplemented with a daily oral dose of 15,000 IU vitamin A palmitate have
shown, on average, a slower rate of deterioration of retinal function when the intervention
is continued over several years. The purpose of this research is to determine whether
administration of high oral doses of vitamin A can acutely improve cone photoreceptor
function in RP participants as measured by electroretinography (ERG). In this
interventional, non-randomized, prospective, pilot study, 10 participants (five with the
RHO1 gene mutation and five without the mutation) will receive a daily oral dose of 50,000
IU of vitamin A palmitate for 4 weeks, followed by a maintenance dose of 15,000 IU daily for
the subsequent 2 weeks. The primary efficacy outcome is a relative percentage change in ERG
response amplitude subsequent to vitamin A supplementation. A secondary efficacy outcome is
a relative percentage change in implicit time from pre- to post- vitamin A supplementation,
with improvement specified as a shorter response implicit time. Other secondary outcomes
will be improvements in visual field (Humphrey 10-2; sum of thresholds). Safety outcomes
include visual fields, ETDRS visual acuity, intraocular pressure, serum vitamin A level and
liver function tests.

- INCLUSION CRITERIA:

All participants must meet the following criteria to participate in the study.

1. Men and women age 18 years of age and older. (Children will be excluded since there
is a higher incidence of vitamin A toxicity in the pediatric population.)

2. Diagnoses of typical RP of all genetic subtypes (simplex, autosomal dominant,
autosomal recessive, and X-linked), as determined primarily by abnormally reduced ERG
rod response amplitudes that are relatively more affected than cone ERG amplitudes.

3. Mutation in the RHO1 gene as determined by genotyping.

4. Participants in whom flicker ERG can be measured reliably (standard flicker ERG
amplitude greater than 2 microV).

5. Willingness to use contraception for the duration of the study.

6. Understood and signed consent.

EXCLUSION CRITERIA:

Participants with the following conditions will be excluded from study.

1. Participants with syndromic RP (i.e., Ushers syndrome).

2. Have abnormal liver function (greater than ULN ALT, AST, Alkaline Phosphate, or Total
Bilirubin).

3. Hematocrit greater than 1.5 x ULN

4. Have abnormal kidney function (greater than1.5 mg/dL serum creatinine).

5. Currently or has taken greater than 15,000 IU/day vitamin A supplementation within 6
months of the first screening visit.

6. Is pregnant or lactating (due to evidence that sugests excessive intake of vitamin A
could be tertogenic in humans and affect the content of breast milk).

7. Currently or has taken greater than 400 IU/day of vitamin E supplementation within 6
months of enrollment.

8. Vitamin A serum level exceeding 150 microg/dL.