Physicians' Health Study II (PHS II)

Mass General Brigham

Status: Completed

Conditions: Cognitive Decline; Cancer; Prostate Cancer; Eye Disease; Cardiovascular Disease; Colorectal Cancer

Treatments: Dietary Supplement: Multivitamin; Dietary Supplement: Beta-carotene; Dietary Supplement: Vitamin C; Dietary Supplement: Vitamin E

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00270647

BWH-83-00405

CDR0000448630

R01CA097193 (U.S. NIH Grant/Contract)

BWH-1999-P-003318

BWH-1999-P-003315

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 14,641 patients

Sex: Male

Ages: 50+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

INCLUSION CRITERIA

1. DISEASE CHARACTERISTICS:

   • Healthy male physicians practicing in the United States
   • Prior participation in the Physicians' Health Study I allowed

2. 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

3. PRIOR CONCURRENT THERAPY:

   • No other concurrent vitamin and/or multivitamin supplementation
   • No concurrent vitamin K-depleting anticoagulants (e.g., warfarin)

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Triple Blind

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14,641 participants in 4 patient groups

Vitamin E

Experimental group

Description:

Active or placebo vitamin E

Treatment:

Dietary Supplement: Vitamin E

Vitamin C

Experimental group

Description:

Active or placebo vitamin C

Treatment:

Dietary Supplement: Vitamin C

Multivitamin

Experimental group

Description:

Active or placebo multivitamin

Treatment:

Dietary Supplement: Multivitamin

Beta-carotene

Experimental group

Description:

Active or placebo beta-carotene

Treatment:

Dietary Supplement: Beta-carotene