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

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00309387

Acronym

CTNS

Enrollment

1020

Registered

2006-03-31

Start date

1995-05-31

Completion date

2007-05-31

Last updated

2013-05-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cataract

Keywords

Cataract, Nutritional supplements

Brief summary

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.

Detailed description

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.

Interventions

DIETARY_SUPPLEMENTCentrum

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

OTHERPlacebo

placebo tablets manufactured to mimic Centrum tablets.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

55 Years to 75 Years

Healthy volunteers

Yes

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

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants Showing Development or Progression of Age-related Cataract or Undergoing Cataract Surgery During Follow-up	at yearly intervals from baseline for approximately ten years	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.

Secondary

Measure	Time frame	Description
Number of Participants Showing Development or Progression of Nuclear Lens Opacities	at yearly intervals from baseline for approximately ten years	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 Showing Development or Progression of Cortical Lens Opacities	at yearly intervals from baseline for approximately ten years	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 Showing Development or Progression of Posterior Subcapsular Opacities	at yearly intervals from baseline for approximately ten years	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 Undergoing Cataract Surgery	at 6 month intervals from baseline for approximately 10 yrs	number of participants undergoing cataract surgery in at least one eligible eye during follow-up
Number of Participants With a Decrease in Visual Acuity	at 6 month intervals from baseline for approximately 10 yrs	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

Countries

Italy

Participant flow

Recruitment details

1020 participants were enrolled from January 8, 1996 through April 10, 1998 at the Institute of Ophthalmology of the University of Parma, Parma, Italy

Pre-assignment details

Potential participants had to complete a 1-month placebo run-in period (use of \> 75% of the run-in tablets) before randomization

Participants by arm

Arm	Count
Treatment	510
Placebo	510
Total	1,020

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Death	72	73
Overall Study	Lost to Follow-up	70	86

Baseline characteristics

Characteristic	Placebo	Treatment	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	370 Participants	371 Participants	741 Participants
Age, Categorical Between 18 and 65 years	140 Participants	139 Participants	279 Participants
Age Continuous	67.7 years STANDARD_DEVIATION 4.97	67.7 years STANDARD_DEVIATION 4.82	67.7 years STANDARD_DEVIATION 4.89
Region of Enrollment Italy	510 participants	510 participants	1020 participants
Sex: Female, Male Female	226 Participants	233 Participants	459 Participants
Sex: Female, Male Male	284 Participants	277 Participants	561 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	39 / 510	38 / 510
serious Total, serious adverse events	363 / 510	397 / 510

Outcome results

Primary

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.

Time frame: at yearly intervals from baseline for approximately ten years

Population: Intention to treat analysis

Arm	Measure	Value (NUMBER)
Treatment	Number of Participants Showing Development or Progression of Age-related Cataract or Undergoing Cataract Surgery During Follow-up	227 participants
Placebo	Number of Participants Showing Development or Progression of Age-related Cataract or Undergoing Cataract Surgery During Follow-up	255 participants

p-value: 0.0395% CI: [0.68, 0.98]Regression, Cox

Secondary

Number of Participants Showing Development or Progression of Cortical Lens Opacities

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

Time frame: at yearly intervals from baseline for approximately ten years