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

Retinitis Pigmentosa Clinical Trial

Official title:

Randomized Clinical Trial for Retinitis Pigmentosa

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00346333
• Other study ID #: NEI-126
• Status: Completed
• Phase: Phase 3
• First received: June 27, 2006
• Last updated: December 12, 2013
• Start date: July 2003
• Est. completion date: December 2008

Study information

• Verified date: December 2013
• Source: National Eye Institute (NEI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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 information / eligibility

• Status: Completed
• Enrollment: 240
• Est. completion date: December 2008
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Retinitis
• Retinitis Pigmentosa

Intervention

Drug:
• Lutein
12mg/d

Dietary Supplement:
• Cornstarch control
Daily intake of cornstarch control plus 15,000 IU/d Vitamin A palmitate

Locations

Country	Name	City	State
United States	Berman Gund Laboratory for the Study of Retinal Degenerations, Harvard Medical School ,Massachusetts Eye & Ear Infirmary	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
National Eye Institute (NEI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. 201 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Central Visual Field (vf) Change Assessed Using the 30-2 Program of the Humphrey Field Analyzer (HFA).	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.	assessed at each of 4 annual visits after baseline	No
Secondary	Mid-peripheral Field Change Assessed With the 60-4 Program of the Humphrey Field Analyzer.	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.	assessed at each of 4 annual visits after baseline	No
Secondary	Total Field Change Assessed by the Combined 30-2 and 60-4 Programs of the Humphrey Field Analyzer.	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.	assessed at each of 4 annual visits after baseline	No
Secondary	Annual Change in 30 Hertz(Hz)Electroretinogram(ERG )Amplitude in Natural Log (ln) Microvolts/yr Over a 4 Year Period.	Computer averaged 30 Hz ERG amplitudes in microvolts for those with initial amplitudes of >= 0.68 microvolts. Presented on the ln scale.	assessed at each of 4 annual visits after baseline	No
Secondary	Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity	Annual change in number of letters read.	assessed at each of 4 annual visits after baseline	No