Collaborative Italian-American Clinical Trial of Nutritional Supplements and Age-related Cataract (CTNS) (CTNS)

Collaborative Italian-American Clinical Trial of Nutritional Supplements and Age-related Cataract (CTNS)

Collaborative Italian-American Clinical Trial of Nutritional Supplements and Age-related Cataract (CTNS)

The Collaborative Italian-American Clinical Trial of Nutritional Supplements and Age-related Cataract (CTNS) is a 13-year study designed primarily to evaluate the safety and efficacy of a vitamin-mineral supplement (Centrum) containing recommended daily-allowance dosage (RDA) in preventing age-related cataract or delaying its progression in participants with early or no cataract at baseline.

Despite dramatic increase in the rates of cataract surgery during the last decades, age-related cataract is still responsible for about 50% of cases of severe visual impairment in developing countries, and for high and growing health care costs in western countries. CTNS was designed to complement the U.S. Age-Related Eye Disease Study (AREDS) by evaluating a much broader spectrum of nutrients at RDA dosages. Whereas about 60% of the AREDS control group was taking RDA dose multivitamin supplements, none of the participants in CTNS had taken any type of nutritional supplement for at least one year before the qualification visit. Therefore, the CTNS will be able to evaluate the effect of RDA doses versus no supplementation at all. CTNS and AREDS will use similar procedures, including those for grading the presence and severity of lens changes. CTNS is a randomized,parallel group, placebo controlled, double blinded, single center, intervention trial. Primary Outcomes: photographic evaluation of a prespecified increase from baseline in nuclear, cortical, or posterior subcapsular cataract (PSC) opacity grades or cataract surgery. Secondary Outcomes: increase in type-specific opacity grade, cataract surgery, and visual acuity loss from baseline > or = 15 letters. Patients will be followed for a maximum of 10 years.

Multivitamin/mineral supplement containing US RDA levels of nutrients. 1 tablet a day for the expected duration of follow-up (on average 10 yrs).

Number of Participants Showing Development or Progression of Age-related Cataract or Undergoing Cataract Surgery During Follow-up

number of participants in whom any of the following occur in at least one eligible eye during follow-up: cataract surgery; nuclear opacity: a 1.5 U increase in opalescence from baseline; cortical opacity: a 10% increase in area within a standard 5 mm circle area of the lens from baseline; posterior subcapsular opacity: a 5% increase in area within a standard 5 mm circle area of the lens from baseline.

number of participants with a 1.5 U increase in nuclear opalescence from baseline in at least one eligible eye during follow-up

Number of participants with a 10% increase in area of cortical opacity within a standard central 5 mm circle of the lens from baseline in at least one eligible eye during follow-up

Number of participants with a 5% increase in area of posterior subcapsular opacity within a standard central 5 mm circle of the lens from baseline in at least one eligible eye during follow-up

Number of participants with a decrease in best corrected visual acuity score from baseline of > 15 letters in at least one eligible eye during follow-up

Inclusion Criteria: Clinical and photographic diagnosis of early or no age-related cataract Participants with early cataract must have at least one eligible eye with VA score 20/32 or better Participants with no cataract must have VA score 20/32 or better in both eyes. Exclusion Criteria: Advanced cataract Bilateral aphakia or pseudophakia Any ocular disease or condition that might complicate the future evaluation of cataract Regular use of nutritional supplements Failure to take at least 75% of run-in medication Cancer with evidence of recurrence in the past 5 years Major cerebral or cardiovascular events in past 12 months Current participation to other clinical trials Any condition likely to prevent adherence to CTNS follow-up schedule

CTNS Study Group. The Italian-American Clinical Trial of Nutritional Supplements and Age-Related Cataract (CTNS): design implications. CTNS report no. 1. Control Clin Trials. 2003 Dec;24(6):815-29. doi: 10.1016/s0197-2456(03)00095-3.

Ferrigno L, Aldigeri R, Rosmini F, Sperduto RD, Maraini G; Italian-American Cataract Study Group. Associations between plasma levels of vitamins and cataract in the Italian-American Clinical Trial of Nutritional Supplements and Age-Related Cataract (CTNS): CTNS Report #2. Ophthalmic Epidemiol. 2005 Apr;12(2):71-80. doi: 10.1080/09286580590932815.

Clinical Trial of Nutritional Supplements and Age-Related Cataract Study Group; Maraini G, Williams SL, Sperduto RD, Ferris F, Milton RC, Clemons TE, Rosmini F, Ferrigno L. A randomized, double-masked, placebo-controlled clinical trial of multivitamin supplementation for age-related lens opacities. Clinical trial of nutritional supplements and age-related cataract report no. 3. Ophthalmology. 2008 Apr;115(4):599-607.e1. doi: 10.1016/j.ophtha.2008.01.005.

Maraini G, Williams SL, Sperduto RD, Ferris FL, Milton RC, Clemons TE, Rosmini F, Ferrigno L. Effects of multivitamin/mineral supplementation on plasma levels of nutrients. Report No. 4 of the Italian-American clinical trial of nutritional supplements and age-related cataract. Ann Ist Super Sanita. 2009;45(2):119-27.