Clinical trial NCT00346333: Clinical Trial of Lutein for Patients With Retinitis Pigmentosa Receiving Vitamin A
Official title: Randomized Clinical Trial for Retinitis Pigmentosa
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Retinitis Pigmentosa
Keywords: Retinitis Pigmentosa, Inherited Retinal Degeneration
Lead sponsor: National Eye Institute (NEI)
Sponsor class: NIH
First posted: 2006-06-29
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Central Visual Field (vf) Change Assessed Using the 30-2 Program of the Humphrey Field Analyzer (HFA).
timeFrame: assessed at each of 4 annual visits after baseline
Secondary outcomes:
measure: Mid-peripheral Field Change Assessed With the 60-4 Program of the Humphrey Field Analyzer.
timeFrame: assessed at each of 4 annual visits after baseline
measure: Total Field Change Assessed by the Combined 30-2 and 60-4 Programs of the Humphrey Field Analyzer.
timeFrame: assessed at each of 4 annual visits after baseline
measure: Annual Change in 30 Hertz(Hz)Electroretinogram(ERG )Amplitude in Natural Log (ln) Microvolts/yr Over a 4 Year Period.
timeFrame: assessed at each of 4 annual visits after baseline
measure: Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity
timeFrame: assessed at each of 4 annual visits after baseline
Other outcomes:
Locations:
city: Boston
country: United States
facility: Berman Gund Laboratory for the Study of Retinal Degenerations, Harvard Medical School ,Massachusetts Eye & Ear Infirmary
state: Massachusetts
Study officials:
affiliation: Harvard Medical School (HMS and HSDM)
name: Eliot L Berson, MD
role: STUDY_CHAIR
References:
citation: Berson EL, Rosner B, Sandberg MA, Weigel-DiFranco C, Brockhurst RJ, Hayes KC, Johnson EJ, Anderson EJ, Johnson CA, Gaudio AR, Willett WC, Schaefer EJ. Clinical trial of lutein in patients with retinitis pigmentosa receiving vitamin A. Arch Ophthalmol. 2010 Apr;128(4):403-11. doi: 10.1001/archophthalmol.2010.32.