Clinical trial NCT00270647: Physicians' Health Study II
Official title: Physicians' Health Study II: Trial of Vitamins in the Chemoprevention of Cancer, CVD, and Eye Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cancer
Prostate Cancer
Colorectal Cancer
Cardiovascular Disease
Eye Disease
Cognitive Decline
Keywords: cancer
prostate cancer
colorectal cancer
cardiovascular disease
eye disease
cognitive decline
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-12-28
Enrollment: 14641
Sex: MALE
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility 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)

Primary outcomes:
measure: Prostate cancer
timeFrame: Ongoing
measure: Total cancer
timeFrame: Ongoing
measure: Major cardiovascular events
timeFrame: Ongoing
Secondary outcomes:
measure: Cataract
timeFrame: Ongoing
measure: Age-related macular degeneration
timeFrame: Ongoing
measure: Early cognitive decline
timeFrame: Ongoing
measure: Myocardial infarction
timeFrame: Ongoing
measure: Stroke
timeFrame: Ongoing
measure: Colorectal cancer
timeFrame: Ongoing
Other outcomes:
Locations:
Study officials:
affiliation: Brigham and Women's Hospital
name: J. Michael Gaziano, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Christen WG, Gaziano JM, Hennekens CH. Design of Physicians' Health Study II--a randomized trial of beta-carotene, vitamins E and C, and multivitamins, in prevention of cancer, cardiovascular disease, and eye disease, and review of results of completed trials. Ann Epidemiol. 2000 Feb;10(2):125-34. doi: 10.1016/s1047-2797(99)00042-3.
citation: Gaziano JM, Glynn RJ, Christen WG, Kurth T, Belanger C, MacFadyen J, Bubes V, Manson JE, Sesso HD, Buring JE. Vitamins E and C in the prevention of prostate and total cancer in men: the Physicians' Health Study II randomized controlled trial. JAMA. 2009 Jan 7;301(1):52-62. doi: 10.1001/jama.2008.862. Epub 2008 Dec 9.
citation: Sesso HD, Buring JE, Christen WG, Kurth T, Belanger C, MacFadyen J, Bubes V, Manson JE, Glynn RJ, Gaziano JM. Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trial. JAMA. 2008 Nov 12;300(18):2123-33. doi: 10.1001/jama.2008.600. Epub 2008 Nov 9.
citation: Christen WG, Glynn RJ, Sesso HD, Kurth T, Macfadyen J, Bubes V, Buring JE, Manson JE, Gaziano JM. Vitamins E and C and medical record-confirmed age-related macular degeneration in a randomized trial of male physicians. Ophthalmology. 2012 Aug;119(8):1642-9. doi: 10.1016/j.ophtha.2012.01.053. Epub 2012 Apr 13.
citation: Christen WG, Glynn RJ, Sesso HD, Kurth T, MacFadyen J, Bubes V, Buring JE, Manson JE, Gaziano JM. Age-related cataract in a randomized trial of vitamins E and C in men. Arch Ophthalmol. 2010 Nov;128(11):1397-405. doi: 10.1001/archophthalmol.2010.266.
citation: Grodstein F, Kang JH, Glynn RJ, Cook NR, Gaziano JM. A randomized trial of beta carotene supplementation and cognitive function in men: the Physicians' Health Study II. Arch Intern Med. 2007 Nov 12;167(20):2184-90. doi: 10.1001/archinte.167.20.2184.
citation: Juraschek SP, Gaziano JM, Glynn RJ, Gomelskaya N, Bubes VY, Buring JE, Shmerling RH, Sesso HD. Effects of vitamin C supplementation on gout risk: results from the Physicians' Health Study II trial. Am J Clin Nutr. 2022 Sep 2;116(3):812-819. doi: 10.1093/ajcn/nqac140.
citation: Rautiainen S, Gaziano JM, Christen WG, Bubes V, Kotler G, Glynn RJ, Manson JE, Buring JE, Sesso HD. Effect of Baseline Nutritional Status on Long-term Multivitamin Use and Cardiovascular Disease Risk: A Secondary Analysis of the Physicians' Health Study II Randomized Clinical Trial. JAMA Cardiol. 2017 Jun 1;2(6):617-625. doi: 10.1001/jamacardio.2017.0176.
citation: Wang L, Sesso HD, Glynn RJ, Christen WG, Bubes V, Manson JE, Buring JE, Gaziano JM. Vitamin E and C supplementation and risk of cancer in men: posttrial follow-up in the Physicians' Health Study II randomized trial. Am J Clin Nutr. 2014 Sep;100(3):915-23. doi: 10.3945/ajcn.114.085480. Epub 2014 Jul 9.
citation: Grodstein F, O'Brien J, Kang JH, Dushkes R, Cook NR, Okereke O, Manson JE, Glynn RJ, Buring JE, Gaziano M, Sesso HD. Long-term multivitamin supplementation and cognitive function in men: a randomized trial. Ann Intern Med. 2013 Dec 17;159(12):806-14. doi: 10.7326/0003-4819-159-12-201312170-00006.
citation: Christen WG, Glynn RJ, Manson JE, MacFadyen J, Bubes V, Schvartz M, Buring JE, Sesso HD, Gaziano JM. Effects of multivitamin supplement on cataract and age-related macular degeneration in a randomized trial of male physicians. Ophthalmology. 2014 Feb;121(2):525-34. doi: 10.1016/j.ophtha.2013.09.038. Epub 2013 Nov 20.
citation: Gaziano JM, Sesso HD, Christen WG, Bubes V, Smith JP, MacFadyen J, Schvartz M, Manson JE, Glynn RJ, Buring JE. Multivitamins in the prevention of cancer in men: the Physicians' Health Study II randomized controlled trial. JAMA. 2012 Nov 14;308(18):1871-80. doi: 10.1001/jama.2012.14641.
citation: Sesso HD, Christen WG, Bubes V, Smith JP, MacFadyen J, Schvartz M, Manson JE, Glynn RJ, Buring JE, Gaziano JM. Multivitamins in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trial. JAMA. 2012 Nov 7;308(17):1751-60. doi: 10.1001/jama.2012.14805.