Physicians' Health Study II

Study Overview
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Brief Summary
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The use of vitamin E, vitamin C, beta carotene, and/or multivitamins may keep cancer, cardiovascular disease, eye diseases, or cognitive decline from occurring. This randomized clinical trial studied vitamin E, vitamin C, beta carotene, and/or multivitamins to see how well they work compared with placebos in preventing cancer, cardiovascular disease, eye disease, and cognitive decline in male doctors aged 50 years and older.

Detailed Description
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OBJECTIVES: Primary To determine whether vitamin E every other day reduces the risk of developing prostate cancer in older healthy male physicians. To determine whether daily vitamin C and/or a multivitamin reduces the risk of total cancer in these participants. To determine whether vitamin E every other day, vitamin C daily, or a multivitamin daily reduces the risk of major cardiovascular events in these participants. Secondary To determine whether vitamin E and/or multivitamins reduce the risk of developing total cancer, colon cancer, and colon polyps in these participants. To determine whether vitamin E, vitamin C, or multivitamins reduce the risk of myocardial infarction and stroke in these participants. To determine whether vitamin E, vitamin C, or multivitamins reduce the risk of age-related macular degeneration or cataract in these participants. To determine whether vitamin E, vitamin C, or multivitamins reduce the risk of early cognitive decline in participants aged 65 and over. The Physicians' Health Study II was a randomized, double-blind, placebo-controlled, factorial trial that began in 1997 and ended in 2011. It was designed to test four supplements -- (1) alternate-day vitamin E (400 international units of synthetic alpha-tocopherol) or its placebo; (2) daily vitamin C (500 mg synthetic ascorbic acid) or its placebo; (3) a daily multivitamin (Centrum Silver) or its placebo; and (4) alternate-day beta carotene (50 mg Lurotin) or its placebo -- in the prevention of cancer, cardiovascular disease, eye disease, and early cognitive decline among 14,641 male physicians aged 50 years or older. Participants were randomly assigned in a 2x2x2x2 factorial trial to receive combinations of the four active supplements or their placebos. Pills and/or packaging were provided by BASF Corporation, Pfizer (formerly Wyeth, American Home Products, and Lederle), and DSM Nutritional Products (formerly Roche Vitamins). The beta-carotene component was discontinued on March 8, 2003; the vitamin E and vitamin C components ended as scheduled on August 31, 2007; and the multivitamin component ended on June 1, 2011.

Official Title
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Physicians' Health Study II: Trial of Vitamins in the Chemoprevention of Cancer, CVD, and Eye Disease

Conditions
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Cancer, Prostate Cancer, Colorectal Cancer, Cardiovascular Disease, Eye Disease, Cognitive Decline

Intervention / Treatment
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* Dietary Supplement: Vitamin E
* Dietary Supplement: Vitamin C
* Dietary Supplement: Multivitamin
* Dietary Supplement: Beta-carotene


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA DISEASE CHARACTERISTICS: Healthy male physicians practicing in the United States Prior participation in the Physicians' Health Study I allowed PATIENT CHARACTERISTICS: Aged 50 years and over No history of serious illness that would preclude study participation No history of significant adverse events (e.g., rash or allergic reaction) attributed to study agents PRIOR CONCURRENT THERAPY: No other concurrent vitamin and/or multivitamin supplementation No concurrent vitamin K-depleting anticoagulants (e.g., warfarin)

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin E<br>Active or placebo vitamin E | Dietary Supplement: Vitamin E<br>* 400 IU synthetic alpha-tocopherol or its placebo on alternate days (provided by BASF)<br>|
| Experimental: Vitamin C<br>Active or placebo vitamin C | Dietary Supplement: Vitamin C<br>* 500 mg synthetic ascorbic acid or its placebo daily (provided by BASF)<br>|
| Experimental: Multivitamin<br>Active or placebo multivitamin | Dietary Supplement: Multivitamin<br>* Centrum Silver or its placebo daily (provided by Pfizer (formerly Wyeth, American Home Products, and Lederle))<br>|
| Experimental: Beta-carotene<br>Active or placebo beta-carotene | Dietary Supplement: Beta-carotene<br>* 50 mg Lurotin or placebo on alternate days (provided by BASF)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prostate cancer |  | Ongoing | 
| Total cancer |  | Ongoing | 
| Major cardiovascular events |  | Ongoing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cataract |  | Ongoing | 
| Age-related macular degeneration |  | Ongoing | 
| Early cognitive decline |  | Ongoing | 
| Myocardial infarction |  | Ongoing | 
| Stroke |  | Ongoing | 
| Colorectal cancer |  | Ongoing | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cancer, prostate cancer, colorectal cancer, cardiovascular disease, eye disease, cognitive decline