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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Eye Institute (NEI)
ClinicalTrials.gov Identifier:
NCT00346333
First received: June 27, 2006
Last updated: December 12, 2013
Last verified: December 2013
  Purpose

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


Condition Intervention Phase
Retinitis Pigmentosa
Drug: Lutein
Dietary Supplement: Cornstarch control
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized Clinical Trial for Retinitis Pigmentosa

Resource links provided by NLM:


Further study details as provided by National Eye Institute (NEI):

Primary Outcome Measures:
  • Central Visual Field (vf) Change Assessed Using the 30-2 Program of the Humphrey Field Analyzer (HFA). [ Time Frame: assessed at each of 4 annual visits after baseline ] [ Designated as safety issue: No ]
    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:
  • Mid-peripheral Field Change Assessed With the 60-4 Program of the Humphrey Field Analyzer. [ Time Frame: assessed at each of 4 annual visits after baseline ] [ Designated as safety issue: No ]
    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. [ Time Frame: assessed at each of 4 annual visits after baseline ] [ Designated as safety issue: No ]
    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.

  • Annual Change in 30 Hertz(Hz)Electroretinogram(ERG )Amplitude in Natural Log (ln) Microvolts/yr Over a 4 Year Period. [ Time Frame: assessed at each of 4 annual visits after baseline ] [ Designated as safety issue: No ]
    Computer averaged 30 Hz ERG amplitudes in microvolts for those with initial amplitudes of >= 0.68 microvolts. Presented on the ln scale.

  • Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity [ Time Frame: assessed at each of 4 annual visits after baseline ] [ Designated as safety issue: No ]
    Annual change in number of letters read.


Enrollment: 240
Study Start Date: July 2003
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lutein plus 15,000 IU/d Vitamin A
Daily intake of 12mg of Lutein plus 15,000 IU/d of Vitamin A palmitate
Drug: Lutein
12mg/d
Placebo Comparator: Control plus 15,000 IU/d Vitamin A
Daily intake of cornstarch control plus 15,000 IU/d Vitamin A palmitate
Dietary Supplement: Cornstarch control
Daily intake of cornstarch control plus 15,000 IU/d Vitamin A palmitate

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

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00346333

Locations
United States, Massachusetts
Berman Gund Laboratory for the Study of Retinal Degenerations, Harvard Medical School ,Massachusetts Eye & Ear Infirmary
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Investigators
Study Chair: Eliot L Berson, MD Harvard Medical School
  More Information

Publications:
Responsible Party: National Eye Institute (NEI)
ClinicalTrials.gov Identifier: NCT00346333     History of Changes
Other Study ID Numbers: NEI-126
Study First Received: June 27, 2006
Results First Received: June 18, 2012
Last Updated: December 12, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by National Eye Institute (NEI):
Retinitis Pigmentosa, Inherited Retinal Degeneration

Additional relevant MeSH terms:
Retinitis Pigmentosa
Retinitis
Retinal Diseases
Eye Diseases
Eye Diseases, Hereditary
Retinal Dystrophies
Retinal Degeneration
Genetic Diseases, Inborn
Vitamins
Vitamin A
Retinol palmitate
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Anticarcinogenic Agents
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014