search
Back to results

Physicians' Health Study II (PHS II)

Primary Purpose

Cancer, Prostate Cancer, Colorectal Cancer

Status
Completed
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Vitamin E
Vitamin C
Multivitamin
Beta-carotene
Sponsored by
Brigham and Women's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Cancer focused on measuring cancer, prostate cancer, colorectal cancer, cardiovascular disease, eye disease, cognitive decline

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)MaleAccepts Healthy Volunteers

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)

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm Type

    Experimental

    Experimental

    Experimental

    Experimental

    Arm Label

    Vitamin E

    Vitamin C

    Multivitamin

    Beta-carotene

    Arm Description

    Active or placebo vitamin E

    Active or placebo vitamin C

    Active or placebo multivitamin

    Active or placebo beta-carotene

    Outcomes

    Primary Outcome Measures

    Prostate cancer
    Total cancer
    Major cardiovascular events

    Secondary Outcome Measures

    Cataract
    Age-related macular degeneration
    Early cognitive decline
    Myocardial infarction
    Stroke
    Colorectal cancer

    Full Information

    First Posted
    December 27, 2005
    Last Updated
    February 26, 2018
    Sponsor
    Brigham and Women's Hospital
    Collaborators
    National Cancer Institute (NCI)
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT00270647
    Brief Title
    Physicians' Health Study II
    Acronym
    PHS II
    Official Title
    Physicians' Health Study II: Trial of Vitamins in the Chemoprevention of Cancer, CVD, and Eye Disease
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    February 2018
    Overall Recruitment Status
    Completed
    Study Start Date
    July 1997 (undefined)
    Primary Completion Date
    June 2011 (Actual)
    Study Completion Date
    June 2011 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Brigham and Women's Hospital
    Collaborators
    National Cancer Institute (NCI)

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Cancer, Prostate Cancer, Colorectal Cancer, Cardiovascular Disease, Eye Disease, Cognitive Decline
    Keywords
    cancer, prostate cancer, colorectal cancer, cardiovascular disease, eye disease, cognitive decline

    7. Study Design

    Primary Purpose
    Prevention
    Study Phase
    Not Applicable
    Interventional Study Model
    Factorial Assignment
    Masking
    ParticipantInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    14641 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Vitamin E
    Arm Type
    Experimental
    Arm Description
    Active or placebo vitamin E
    Arm Title
    Vitamin C
    Arm Type
    Experimental
    Arm Description
    Active or placebo vitamin C
    Arm Title
    Multivitamin
    Arm Type
    Experimental
    Arm Description
    Active or placebo multivitamin
    Arm Title
    Beta-carotene
    Arm Type
    Experimental
    Arm Description
    Active or placebo beta-carotene
    Intervention Type
    Dietary Supplement
    Intervention Name(s)
    Vitamin E
    Intervention Description
    400 IU synthetic alpha-tocopherol or its placebo on alternate days (provided by BASF)
    Intervention Type
    Dietary Supplement
    Intervention Name(s)
    Vitamin C
    Intervention Description
    500 mg synthetic ascorbic acid or its placebo daily (provided by BASF)
    Intervention Type
    Dietary Supplement
    Intervention Name(s)
    Multivitamin
    Intervention Description
    Centrum Silver or its placebo daily (provided by Pfizer (formerly Wyeth, American Home Products, and Lederle))
    Intervention Type
    Dietary Supplement
    Intervention Name(s)
    Beta-carotene
    Intervention Description
    50 mg Lurotin or placebo on alternate days (provided by BASF)
    Primary Outcome Measure Information:
    Title
    Prostate cancer
    Time Frame
    Ongoing
    Title
    Total cancer
    Time Frame
    Ongoing
    Title
    Major cardiovascular events
    Time Frame
    Ongoing
    Secondary Outcome Measure Information:
    Title
    Cataract
    Time Frame
    Ongoing
    Title
    Age-related macular degeneration
    Time Frame
    Ongoing
    Title
    Early cognitive decline
    Time Frame
    Ongoing
    Title
    Myocardial infarction
    Time Frame
    Ongoing
    Title
    Stroke
    Time Frame
    Ongoing
    Title
    Colorectal cancer
    Time Frame
    Ongoing

    10. Eligibility

    Sex
    Male
    Minimum Age & Unit of Time
    50 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    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)
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    J. Michael Gaziano, MD, MPH
    Organizational Affiliation
    Brigham and Women's Hospital
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    10691066
    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.
    Results Reference
    background
    PubMed Identifier
    19066368
    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.
    Results Reference
    result
    PubMed Identifier
    18997197
    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.
    Results Reference
    result
    PubMed Identifier
    22503302
    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.
    Results Reference
    result
    PubMed Identifier
    21060040
    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.
    Results Reference
    result
    PubMed Identifier
    17998490
    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.
    Results Reference
    result
    PubMed Identifier
    35575611
    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.
    Results Reference
    derived
    PubMed Identifier
    28384735
    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.
    Results Reference
    derived
    PubMed Identifier
    25008853
    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.
    Results Reference
    derived
    PubMed Identifier
    24490265
    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.
    Results Reference
    derived
    PubMed Identifier
    24268861
    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.
    Results Reference
    derived
    PubMed Identifier
    23162860
    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. Erratum In: JAMA. 2014 Aug 6;312(5):560.
    Results Reference
    derived
    PubMed Identifier
    23117775
    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.
    Results Reference
    derived

    Learn more about this trial

    Physicians' Health Study II

    We'll reach out to this number within 24 hrs