Clinical Trial of Lutein for Patients With Retinitis Pigmentosa Receiving Vitamin A

Phase 3

Completed

Conditions: Retinitis Pigmentosa

Interventions: Dietary Supplement: Cornstarch control
Drug: Lutein

Registration Number: NCT00346333

Lead Sponsor: National Eye Institute (NEI)

Brief Summary: The purpose of this trial is to determine whether lutein in addition to vitamin A will slow the course of retinitis pigmentosa.

Detailed Description: Retinitis pigmentosa (RP) is a group of inherited retinal degenerations with a worldwide prevalence of approximately 1 in 4,000. Patients typically report night blindness and difficulty with mid-peripheral visual field in adolescence. As the condition progresses, they lose far peripheral visual field. Most patients have reductions in central vision by 60 years if left untreated. Vitamin A palmitate, 15,000 International Units (IU)/d and an omega-3 rich diet have been shown to slow the progression of this condition among adults with the typical forms.(see Archives of Ophthalmology,111:761-772,1993 ; Archives of Ophthalmology 122: 1306-1314, 2004; Archives of Ophthalmology 130(6):701-711,2013).

The present study was a randomized, controlled, double-masked trial with a planned duration of 5 years.Two hundred and forty adults with the typical forms of RP were assigned to either lutein 12mg/d or a control group. Patients in both groups received 15,000 IU/day of vitamin A palmitate in addition to the supplement under study. Participants agreed not to know the contents of the supplement or their group assignment until the end of the trial. The main outcome measurement was the total point score for the 30-2 program of the Humphrey Field analyzer (HFA). In addition,the total point score for the 60-4 program ,the total point score of the 30-2 and 60-4 programs combined, computer-averaged 30-Hz cone Electroretinogram (ERG) amplitude and Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity were measured annually as secondary endpoints.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 240

Inclusion Criteria

Ocular Criteria

RP, typical forms(i.e. elevated final dark adaptation threshold,retinal arteriolar narrowing,and reduced and delayed full-field ERGs).
Best-corrected visual acuity 20/100 or better
HFA program 30-2 total point score >= 250 decibels(dB)to a size V white test light
No confounding ocular disease such as glaucoma,uveitis,diabetic retinopathy,posterior subcapsular cataract more than 11% of total lens area (ie equivalent to P3 on Lens Opacity Classification System III)and pupil diameter after dilation less than 6 mm.

Dietary Criteria

Fruit and vegetable intake < 10 servings/d
Spinach or kale intake < 1 serving/d, i.e. <1/2 cup of cooked spinach or kale per day
Dietary lutein intake <=5.4 mg/d as estimated from food frequency questionnaire
No intake of cod liver oil or omega-3 capsules
Dietary preformed vitamin A intake <= 10,000 IU/d
Supplement intake <= 5,000 IU/d of Vitamin A and <= 30 IU/d of Vitamin E
Consumption <= 3 alcoholic beverages/d

Medical and other criteria

Age 18-60 y
Body mass index < 40 and weight >= 5th percentile for age,gender,and height
Serum retinol level <= 100 micrograms/deciliter and serum retinyl ester level <= 380 nanomoles/Liter
Serum cholesterol < 300 micrograms/deciliter and serum triglyceride level <400 micrograms/deciliter
No clinically significant abnormality on blood cell count, glucose level, blood urea nitrogen level, serum lipid panel results or serum liver function profile.
Not pregnant or planning to become pregnant
Not smoking currently
Agreed not to know tablet content or course of condition until the end of the trial.
No other disease which might affect absorption or metabolism of lutein or vitamin A.
Only one patient per family was accepted into the study.

Exclusion Criteria

Women who are pregnant or planning to become pregnant (Vitamin A supplements can increase the risk of birth defects.)
Current participation in another clinical trial for RP
Patients with atypical forms such as paravenous RP, pericentral RP, sector RP,unilateral RP,Refsum disease, Bardet-Biedl syndrome, retinitis punctata albescens and cone-rod dystrophy were excluded as were patients with RP and profound congenital deafness.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control plus 15,000 IU/d Vitamin A	Cornstarch control	Daily intake of cornstarch control plus 15,000 IU/d Vitamin A palmitate
Lutein plus 15,000 IU/d Vitamin A	Lutein	Daily intake of 12mg of Lutein plus 15,000 IU/d of Vitamin A palmitate

Primary Outcome Measures

Name	Time	Method
Central Visual Field (vf) Change Assessed Using the 30-2 Program of the Humphrey Field Analyzer (HFA).	assessed at each of 4 annual visits after baseline	Sum of visual field sensitivity readings in decibel(dB) to a size V target out to the 30 degree meridian in each direction of the visual field. The value presented represents annual change in dB over 4 years.

Secondary Outcome Measures

Name	Time	Method
Mid-peripheral Field Change Assessed With the 60-4 Program of the Humphrey Field Analyzer.	assessed at each of 4 annual visits after baseline	Sum of visual field sensitivity readings in dB to a size V target from the 30 degree meridian to the 60 degree meridian in each direction of the visual field. The value presented represents annual change in dB over 4 years.
Total Field Change Assessed by the Combined 30-2 and 60-4 Programs of the Humphrey Field Analyzer.	assessed at each of 4 annual visits after baseline	Sum of visual field sensitivity readings in dB to a size V target obtained with the 30-2 and 60-4 programs of the Humphrey Field Analyzer combined for those patients on whom both measures were available.
Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity	assessed at each of 4 annual visits after baseline	Annual change in number of letters read.
Annual Change in 30 Hertz(Hz)Electroretinogram(ERG )Amplitude in Natural Log (ln) Microvolts/yr Over a 4 Year Period.	assessed at each of 4 annual visits after baseline	Computer averaged 30 Hz ERG amplitudes in microvolts for those with initial amplitudes of \>= 0.68 microvolts. Presented on the ln scale.

Trial Locations

Locations (1): Berman Gund Laboratory for the Study of Retinal Degenerations, Harvard Medical School ,Massachusetts Eye & Ear Infirmary
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Boston, Massachusetts, United States