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

• Sponsor: National Eye Institute (NEI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00309387
• Collaborator: (none)
• Enrollment: 1,020
• Location: 1
• Arms: 2
• Duration (Months): 144
• Patients Per Site Per Month: 7.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cataract	Dietary Supplement: Centrum; Other: Placebo	Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1020 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Collaborative Italian-American Clinical Trial of Nutritional Supplements and Age-related Cataract (CTNS)
• Study Start Date: May 1, 1995
• Actual Primary Completion Date: May 1, 2007
• Actual Study Completion Date: May 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Centrum multivitamin-mineral supplement. RDA dosage. 1 tablet a day for the whole study duration.	Dietary Supplement: Centrum; Multivitamin/mineral supplement containing US RDA levels of nutrients. 1 tablet a day for the expected duration of follow-up (on average 10 yrs).
Placebo Comparator: placebo placebo pills. One tablet a day for the whole study duration.	Other: Placebo; placebo tablets manufactured to mimic Centrum tablets.

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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

2. 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

3. 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

4. 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

5. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 55 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dpt. Scienze Otorino-Odonto Oftalmologiche, University of Parma	Parma		Italy	43100

Sponsors and Collaborators

• National Eye Institute (NEI)

Investigators

• Study Chair: Giovanni Maraini, MD, University of Parma
• Principal Investigator: Robert D Sperduto, MD, National Eye Institute (NEI)

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.

• Responsible Party: National Eye Institute (NEI)
• ClinicalTrials.gov Identifier: NCT00309387
• Other Study ID Numbers: NEI-110
• First Posted: Mar 31, 2006
• Last Update Posted: May 6, 2013
• Last Verified: Apr 1, 2013

• Keywords provided by National Eye Institute (NEI): Cataract; Nutritional supplements
• Additional relevant MeSH terms: Cataract

Study Results

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

Arm/Group Title	Treatment	Placebo
Arm/Group Description
Period Title: Overall Study
STARTED	510	510
COMPLETED	368	351
NOT COMPLETED	142	159

Baseline Characteristics

Arm/Group Title	Treatment	Placebo	Total
Arm/Group Description	Total of all reporting groups
Overall Participants	510	510	1020
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	139 27.3%	140 27.5%	279 27.4%
>=65 years	371 72.7%	370 72.5%	741 72.6%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	67.7 (4.82)	67.7 (4.97)	67.7 (4.89)
Sex: Female, Male (Count of Participants)
Female	233 45.7%	226 44.3%	459 45%
Male	277 54.3%	284 55.7%	561 55%
Region of Enrollment (participants) [Number]
Italy	510 100%	510 100%	1020 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Intention to treat analysis

Arm/Group Title	Treatment	Placebo
Arm/Group Description	Centrum	Placebo
Measure Participants	510	510
Number [participants]	227 44.5%	255 50%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.03
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.82
	Confidence Interval	(2-Sided) 95%; 0.68 to 0.98
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Number of Participants Showing Development or Progression of Nuclear Lens Opacities
Description	number of participants with a 1.5 U increase in nuclear opalescence from baseline in at least one eligible eye during follow-up
Time Frame	at yearly intervals from baseline for approximately ten years

Outcome Measure Data

Analysis Population Description

intention to treat

Arm/Group Title	Treatment	Placebo
Arm/Group Description	Centrum	Placebo
Measure Participants	510	510
Number [participants]	84 16.5%	118 23.1%

3. Secondary Outcome

Title	Number of Participants Showing Development or Progression of Cortical Lens Opacities
Description	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

Outcome Measure Data

Analysis Population Description

intention to treat

Arm/Group Title	Treatment	Placebo
Arm/Group Description	Centrum	placebo
Measure Participants	510	510
Number [participants]	96 18.8%	118 23.1%

4. Secondary Outcome

Title	Number of Participants Showing Development or Progression of Posterior Subcapsular Opacities
Description	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
Time Frame	at yearly intervals from baseline for approximately ten years

Outcome Measure Data

Analysis Population Description

intention to treat

Arm/Group Title	Treatment	Placebo
Arm/Group Description	Centrum	Placebo
Measure Participants	510	510
Number [participants]	74 14.5%	37 7.3%

5. Secondary Outcome

Title	Number of Participants Undergoing Cataract Surgery
Description	number of participants undergoing cataract surgery in at least one eligible eye during follow-up
Time Frame	at 6 month intervals from baseline for approximately 10 yrs

Outcome Measure Data

Analysis Population Description

intention to treat

Arm/Group Title	Treatment	Placebo
Arm/Group Description	Centrum	Placebo
Measure Participants	510	510
Number [participants]	88 17.3%	90 17.6%

6. Secondary Outcome

Title	Number of Participants With a Decrease in Visual Acuity
Description	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
Time Frame	at 6 month intervals from baseline for approximately 10 yrs

Outcome Measure Data

Analysis Population Description

intention to treat

Arm/Group Title	Treatment	Placebo
Arm/Group Description	Centrum	Placebo
Measure Participants	510	510
Number [participants]	144 28.2%	139 27.3%

Adverse Events

Time Frame	6 months
Arm/Group Title	Treatment		Placebo
Arm/Group Description
All Cause Mortality
	Treatment		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Treatment		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	363/510 (71.2%)		397/510 (77.8%)
General disorders
death	77/510 (15.1%)		81/510 (15.9%)
hospitalization	286/510 (56.1%)	573	316/510 (62%)	604
Other (Not Including Serious) Adverse Events
	Treatment		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	39/510 (7.6%)		38/510 (7.5%)
Gastrointestinal disorders
upset stomach	17/510 (3.3%)	17	19/510 (3.7%)	19
General disorders
increased weight	3/510 (0.6%)	3	3/510 (0.6%)	3
other	14/510 (2.7%)	14	12/510 (2.4%)	12
Skin and subcutaneous tissue disorders
skin rash	5/510 (1%)	5	4/510 (0.8%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.