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.

Condition	Treatment or Intervention	Phase
Herpes Zoster Postherpetic neuralgia	Vaccine: Varicella-zoster vaccine	Phase III

Further Study Details: 

Expected Total Enrollment:  37200

Primary Hypothesis:

Immunization with live, attenuated (Oka/Merck) varicella-zoster vaccine will significantly reduce the burden of illness associated with herpes zoster (HZ).

Secondary Hypotheses:

Immunization with live, attenuated (Oka/Merck) varicella-zoster vaccine will reduce the incidence of postherpetic neuralgia (PHN).

Primary Outcomes:

The primary outcome is the burden of illness due to HZ defined by the area under the worst pain versus time curve measured during the 6 month period following HZ rash onset in subjects who develop of HZ. The burden of illness outcome is sensitive to the incidence, severity, and duration of HZ-associated pain. The secondary outcome is the incidence of PHN, where PHN is defined as HZ-associated pain rated as greater than or equal to 3 (on a 0 to 10 scale) persisting or appearing more than 30 days after the onset of the HZ rash.

Interventions:

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

Study Abstract:

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; 37,200 subjects over 60 years of age will be randomized at 22 sites to receive either vaccine or placebo. At least one third of the subjects will be 70 years of age or older. Subjects will be followed actively for HZ with monthly automated telephone calls until the last subject enrolled has completed a minimum of three years of follow-up and at least 400 cases of HZ have occurred. Subjects who develop HZ will be evaluated for severity and duration of associated pain, extent and duration of rash, and for changes in quality of life associated with the disease for six months after the onset of HZ rash.

The study was initiated in December 1998. Patient recruitment began in November 1998 at one site, at 20 sites between February 1999 and July 1999, and at one site that was added in January 2000. On September 26, 2001, enrollment in the study was completed with 38,456 randomized subjects. The DSMB will be meeting on October 31, 2002, to review the accrued HZ case information. There have been no safety concerns with the vaccine.

Ages Eligible for Study:  60 Years and above,  Genders Eligible for Study:  Both

Accepts Healthy Volunteers

Criteria

Adults 60 years of age and older, History of Chickenpox, No history of shingles, no current history of immune suppression (e.g. malignancy or neoplastic disease, corticosteroid therapy)

The subject population will consist of male and female veterans and their spouses at VA sites and non-veterans and their spouses at non-VA sites who are 60 years of age or older, have given written informed consent prior to enrollment, and meet the following criteria:

History of varicella or long-term (greater than or equal to 30 years) residence in the continental USA.

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).

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.

No subjects unlikely to adhere to protocol follow-up.

No subjects involved in a conflicting (vaccine or investigational drug) clinical trial.

Alabama
      Birmingham VAMC, Birmingham,  Alabama,  35294,  United States
California
      San Diego VAMC, San Diego,  California,  92161,  United States
      San Diego VAMC, San Diego,  California,  92161,  United States
      Palo Alto VAMC, Palo Alto,  California,  94304,  United States
Colorado
      Denver, Co (NIH), Denver,  Colorado,  80262,  United States
Florida
      James A. Haley VAMC, Tampa,  Florida,  33612,  United States
Illinois
      Edward Hines Jr. VAMC, Hines,  Illinois,  60141,  United States
Kentucky
      University of Kentucky College of Medicine, Lexington,  Kentucky,  40536-0084,  United States
Maryland
      Baltimore VAMC, Baltimore,  Maryland,  21201,  United States
      NIH-NIAID (Bethesda, MD), Bethesda,  Maryland,  20892,  United States
Massachusetts
      Boston VAMC, Boston,  Massachusetts,  02130,  United States
Michigan
      Ann Arbor VAMC, Ann Arbor,  Michigan,  48105,  United States
Minnesota
      Minneapolis VAMC, Minneapolis,  Minnesota,  55417,  United States
Missouri
      Cochran VA Hospital-St. Louis VAMC, St. Louis,  Missouri,  63106,  United States
New Mexico
      Albuquerque VAMC, Albuquerque,  New Mexico,  87108,  United States
New York
      New York VAMC, New York,  New York,  10010,  United States
      Rochester, NY (NIH), Rochester,  New York,  14642,  United States
      Northport VAMC, Northport,  New York,  11768-2290,  United States
North Carolina
      Durham VAMC, Durham,  North Carolina,  27705,  United States
Tennessee
      Vanderbilt University Medical Center, Nashville,  Tennessee,  37232-2581,  United States
Texas
      San Antonio, TX (NIH), San Antonio,  Texas,  78229-3900,  United States
      Baylor College of Medicine, Houston,  Texas,  77030,  United States
Washington
      Seattle VAMC, Seattle,  Washington,  98108,  United States

Study ID Numbers:  403
Record last reviewed:  December 2004
Last Updated:  December 20, 2004
Record first received:  December 29, 2000
ClinicalTrials.gov Identifier:  NCT00007501
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08