Shingles Prevention Study

NCT00007501 | Completed Phase 3 DMC

• 1 other identifier: 403
• Study Type: interventional
• Target: 38,456
• Locations: 1 country
• Sites: 22

Brief Summary

The incidence and severity of HZ (or shingles), as well as the frequency and severity of its complications, increases markedly with increasing age. More than half of all cases occur in persons over the age of 60. Even without complications, HZ can interfere with an elderly patient's ability to perform essential activities of daily living, resulting in a loss of independence that is emotionally devastating and frequently irreversible. The most common complication of HZ in elderly persons is postherpetic neuralgia (PHN), which frequently results in disordered sleep, chronic fatigue, anxiety and severe depression. Antiviral therapy has a modest impact on the acute phase of HZ. However, it does not appear to prevent the development of PHN. This study is a 5.5 year randomized, double-blind, placebo-controlled, efficacy trial to determine whether vaccination with live-attenuated Oka/Merck varicella-zoster decreases the incidence and/or severity of herpes zoster (HZ) and its complications in adults 60 years of age and older.

Conditions

Herpes Zoster; Postherpetic Neuralgia

Keywords

varicella-zoster vaccine

Outcome Measures

Primary Outcomes (1)

• Reduce burden of illness due to herpes zoster (HZ)

  Incidence of postherpetic neuralgia (PHN), where PHN is defined as HZ-associated pain greater than or equal to 3 persisting or appearing more than 30 days after the onset of the HZ rash

Study Arms (2)

Arm 1

EXPERIMENTAL

varicella-zoster vaccine

Biological: Varicella-zoster vaccine

Arm 2

PLACEBO COMPARATOR

vaccine placebo

Biological: Placebo

Interventions

Varicella-zoster vaccine BIOLOGICAL

Immunization with 0.5 ml, live, attenuated (Oka/Merck) varicella-zoster vaccine.

Arm 1

Placebo BIOLOGICAL

Placebo vaccine

Arm 2

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults 60 years of age and older.
• History of Chickenpox.
• Have given written informed consent prior to enrollment.
• History of varicella or long-term (greater than or equal to 30 years) residence in the continental USA.

You may not qualify if:

• No history of shingles, no current history of immune suppression (e.g. malignancy or neoplastic disease, corticosteroid therapy).
• No immunosuppression resulting from disease (e.g., malignancy; HIV infection), corticosteroids (except intermittent topical or inhaled corticosteroid \[greater than 800 mcg/day beclomethasone dipropionate or equivalent\]), or other immunosuppressive/cytotoxic therapy (cancer chemotherapy or organ transplantation).
• No active neoplastic disease (except local skin cancer or other malignancies \[e.g., prostate cancer\] that are stable in the absence of immunosuppressive/cytotoxic therapy).
• No prior Herpes Zoster.
• No prior receipt of varicella vaccine.
• No allergic sensitivity to neomycin.
• No history of anaphylactoid reaction to gelatin.
• No significant underlying illness that would be expected to prevent completion of the study (e.g., life-threatening disease likely to limit survival to less than 5 years).
• Not ambulatory (must not be bed-ridden or homebound).
• No receipt of immune globulin or any other blood product within 3 months before or planned during the 3-5 year study period.
• No receipt of any other immunizations within one month before study vaccination (2 weeks in the case of inactivated influenza vaccines or other non-replicating immunization products \[e.g., dT, pneumococcal vaccine, hepatitis A vaccine, hepatitis B vaccine\]), or scheduled within 6 weeks after study vaccination.
• Not currently receiving antiviral therapy.
• No other condition (e.g., extensive psoriasis, chronic pain syndrome, cognitive impairment, severe hearing loss) that, in the opinion of the investigator, might interfere with the evaluations required by the study.
• No intercurrent illness (e.g., urinary tract infection, influenza) that might interfere with the interpretation of the study.
• No females who are pre-menopausal.

Sponsors & Collaborators

• US Department of Veterans Affairs: lead
• Merck Sharp & Dohme LLC: collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (22)

VA Medical Center, Birmingham

Birmingham, Alabama, 35233, United States

Location

VA Palo Alto Health Care System

Palo Alto, California, 94304-1290, United States

Location

VA San Diego Healthcare System, San Diego

San Diego, California, 92161, United States

Location

University of Colorado

Denver, Colorado, 80262, United States

Location

James A. Haley Veterans Hospital, Tampa

Tampa, Florida, 33612, United States

Location

Edward Hines, Jr. VA Hospital

Hines, Illinois, 60141-5000, United States

Location

VA Medical Center, Lexington

Lexington, Kentucky, 40502, United States

Location

VA Maryland Health Care System, Baltimore

Baltimore, Maryland, 21201, United States

Location

NIH-NIAID (Bethesda, MD)

Bethesda, Maryland, 20892, United States

Location

VA Medical Center, Jamaica Plain Campus

Boston, Massachusetts, 02130, United States

Location

VA Ann Arbor Healthcare System

Ann Arbor, Michigan, 48113, United States

Location

VA Medical Center, Minneapolis

Minneapolis, Minnesota, 55417, United States

Location

VA Medical Center, St Louis

St Louis, Missouri, 63106, United States

Location

New Mexico VA Health Care System, Albuquerque

Albuquerque, New Mexico, 87108-5153, United States

Location

New York Harbor HCS

New York, New York, 10010, United States

Location

VA Medical Center, Northport

Northport, New York, 11768, United States

Location

Rochester, NY (NIH)

Rochester, New York, 14642, United States

Location

VA Medical Center, Durham

Durham, North Carolina, 27705, United States

Location

Vanderbilt University

Nashville, Tennessee, 37212-2637, United States

Location

Baylor University

Houston, Texas, 77030, United States

Location

University of Texas at San Antonio

San Antonio, Texas, 78229, United States

Location

VA Puget Sound Health Care System, Seattle

Seattle, Washington, 98108, United States

Location

Related Publications (8)

• Oxman MN, Levin MJ, Johnson GR, Schmader KE, Straus SE, Gelb LD, Arbeit RD, Simberkoff MS, Gershon AA, Davis LE, Weinberg A, Boardman KD, Williams HM, Zhang JH, Peduzzi PN, Beisel CE, Morrison VA, Guatelli JC, Brooks PA, Kauffman CA, Pachucki CT, Neuzil KM, Betts RF, Wright PF, Griffin MR, Brunell P, Soto NE, Marques AR, Keay SK, Goodman RP, Cotton DJ, Gnann JW Jr, Loutit J, Holodniy M, Keitel WA, Crawford GE, Yeh SS, Lobo Z, Toney JF, Greenberg RN, Keller PM, Harbecke R, Hayward AR, Irwin MR, Kyriakides TC, Chan CY, Chan IS, Wang WW, Annunziato PW, Silber JL; Shingles Prevention Study Group. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med. 2005 Jun 2;352(22):2271-84. doi: 10.1056/NEJMoa051016.

  PMID: 15930418 RESULT

• Simberkoff MS, Arbeit RD, Johnson GR, Oxman MN, Boardman KD, Williams HM, Levin MJ, Schmader KE, Gelb LD, Keay S, Neuzil K, Greenberg RN, Griffin MR, Davis LE, Morrison VA, Annunziato PW; Shingles Prevention Study Group. Safety of herpes zoster vaccine in the shingles prevention study: a randomized trial. Ann Intern Med. 2010 May 4;152(9):545-54. doi: 10.7326/0003-4819-152-9-201005040-00004.

  PMID: 20439572 RESULT

• Levin MJ, Oxman MN, Zhang JH, Johnson GR, Stanley H, Hayward AR, Caulfield MJ, Irwin MR, Smith JG, Clair J, Chan IS, Williams H, Harbecke R, Marchese R, Straus SE, Gershon A, Weinberg A; Veterans Affairs Cooperative Studies Program Shingles Prevention Study Investigators. Varicella-zoster virus-specific immune responses in elderly recipients of a herpes zoster vaccine. J Infect Dis. 2008 Mar 15;197(6):825-35. doi: 10.1086/528696.

  PMID: 18419349 RESULT

• Harbecke R, Oxman MN, Arnold BA, Ip C, Johnson GR, Levin MJ, Gelb LD, Schmader KE, Straus SE, Wang H, Wright PF, Pachucki CT, Gershon AA, Arbeit RD, Davis LE, Simberkoff MS, Weinberg A, Williams HM, Cheney C, Petrukhin L, Abraham KG, Shaw A, Manoff S, Antonello JM, Green T, Wang Y, Tan C, Keller PM; Shingles Prevention Study Group. A real-time PCR assay to identify and discriminate among wild-type and vaccine strains of varicella-zoster virus and herpes simplex virus in clinical specimens, and comparison with the clinical diagnoses. J Med Virol. 2009 Jul;81(7):1310-22. doi: 10.1002/jmv.21506.

  PMID: 19475609 RESULT

• Weinberg A, Zhang JH, Oxman MN, Johnson GR, Hayward AR, Caulfield MJ, Irwin MR, Clair J, Smith JG, Stanley H, Marchese RD, Harbecke R, Williams HM, Chan IS, Arbeit RD, Gershon AA, Schodel F, Morrison VA, Kauffman CA, Straus SE, Schmader KE, Davis LE, Levin MJ; US Department of Veterans Affairs (VA) Cooperative Studies Program Shingles Prevention Study Investigators. Varicella-zoster virus-specific immune responses to herpes zoster in elderly participants in a trial of a clinically effective zoster vaccine. J Infect Dis. 2009 Oct 1;200(7):1068-77. doi: 10.1086/605611.

  PMID: 19712037 RESULT

• Schmader KE, Oxman MN, Levin MJ, Johnson G, Zhang JH, Betts R, Morrison VA, Gelb L, Guatelli JC, Harbecke R, Pachucki C, Keay S, Menzies B, Griffin MR, Kauffman C, Marques A, Toney J, Keller PM, Li X, Chan IS, Annunziato P; Shingles Prevention Study Group. Persistence of the efficacy of zoster vaccine in the shingles prevention study and the short-term persistence substudy. Clin Infect Dis. 2012 Nov 15;55(10):1320-8. doi: 10.1093/cid/cis638. Epub 2012 Jul 24.

  PMID: 22828595 RESULT

• Schmader KE, Johnson GR, Saddier P, Ciarleglio M, Wang WW, Zhang JH, Chan IS, Yeh SS, Levin MJ, Harbecke RM, Oxman MN; Shingles Prevention Study Group. Effect of a zoster vaccine on herpes zoster-related interference with functional status and health-related quality-of-life measures in older adults. J Am Geriatr Soc. 2010 Sep;58(9):1634-41. doi: 10.1111/j.1532-5415.2010.03021.x.

  PMID: 20863322 RESULT

• Morrison VA, Oxman MN, Levin MJ, Schmader KE, Guatelli JC, Betts RF, Gelb LD, Pachucki CT, Keay SK, Menzies B, Griffin MR, Kauffman CA, Marques AR, Toney JF, Simberkoff MS, Serrao R, Arbeit RD, Gnann JW, Greenberg RN, Holodniy M, Keitel WA, Yeh SS, Davis LE, Crawford GE, Neuzil KM, Johnson GR, Zhang JH, Harbecke R, Chan IS, Keller PM, Williams HM, Boardman KD, Silber JL, Annunziato PW; Shingles Prevention Study Group. Safety of zoster vaccine in elderly adults following documented herpes zoster. J Infect Dis. 2013 Aug 15;208(4):559-63. doi: 10.1093/infdis/jit182. Epub 2013 Apr 30.

  PMID: 23633406 RESULT

Related Links

• Related Info

MeSH Terms

Conditions

Herpes Zoster; Neuralgia, Postherpetic

Condition Hierarchy (Ancestors)

Varicella Zoster Virus Infection; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Neuralgia; Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Michael N. Oxman

  VA San Diego Healthcare System, San Diego

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 29, 2000
• First Posted: January 1, 2001
• Study Start: November 1, 1998
• Primary Completion: April 1, 2004
• Study Completion: February 1, 2011
• Last Updated: July 4, 2013

Record last verified: 2013-07

Locations

US (22)