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

NCT ID: NCT00346333

Last Updated: 2014-01-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 240 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-07-31
• Study Completion Date: 2008-12-31

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.

Conditions

Retinitis Pigmentosa

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Lutein plus 15,000 IU/d Vitamin A

Daily intake of 12mg of Lutein plus 15,000 IU/d of Vitamin A palmitate

Group Type: EXPERIMENTAL

Lutein

Intervention Type: DRUG

12mg/d

Control plus 15,000 IU/d Vitamin A

Daily intake of cornstarch control plus 15,000 IU/d Vitamin A palmitate

Group Type: PLACEBO_COMPARATOR

Cornstarch control

Intervention Type: DIETARY_SUPPLEMENT

Daily intake of cornstarch control plus 15,000 IU/d Vitamin A palmitate

Interventions

Lutein

12mg/d

Intervention Type: DRUG

Cornstarch control

Daily intake of cornstarch control plus 15,000 IU/d Vitamin A palmitate

Intervention Type: DIETARY_SUPPLEMENT

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Eye Institute (NEI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Eliot L Berson, MD

Role: STUDY_CHAIR

Harvard Medical School (HMS and HSDM)

Locations

Berman Gund Laboratory for the Study of Retinal Degenerations, Harvard Medical School ,Massachusetts Eye & Ear Infirmary

Boston, Massachusetts, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 20385935 (View on PubMed)

Comander J, Weigel DiFranco C, Sanderson K, Place E, Maher M, Zampaglione E, Zhao Y, Huckfeldt RM, Bujakowska KM, Pierce E. Natural history of retinitis pigmentosa based on genotype, vitamin A/E supplementation, and an electroretinogram biomarker. JCI Insight. 2023 Aug 8;8(15):e167546. doi: 10.1172/jci.insight.167546.

Reference Type: DERIVED

PMID: 37261916 (View on PubMed)

Other Identifiers

NEI-126

Identifier Type: -

Identifier Source: org_study_id