Study examines effectiveness of vaccine to prevent shingles
Volunteer Barbara Culley (left) recently received the shingles vaccine, courtesy of Nurse Pamela Chapin. (Photo by Donna Jones Bailey)
Vanderbilt University Medical Center is on the lookout for 1,800 volunteers to participate in a national study of a vaccine to prevent shingles, a painful skin and nerve infection.
The trial, funded by the Veterans Affairs Cooperative Studies and the National Institute of Allergy and Infectious Diseases (NIAID), will recruit 37,000 volunteers at 21 medical centers throughout the country.
"We are looking for people 60 or older who at some point in their lives have had chickenpox, but have not had a prior outbreak of shingles," said Dr. Marie R. Griffin, Professor of Preventive Medicine and Medicine.
Dr. Peter F. Wright, Professor of Pediatrics in Pediatric Infectious Diseases, is the principal investigator for the study along with co-investigators Griffin and Dr. Deborah W. Robin, Assistant Professor of Medicine.
Shingles, a miserably painful skin and nerve infection affecting up to 500,000 Americans each year, is caused by the herpes zoster virus. Both the incidence and severity of shingles and its complications increase with advancing age. More than half of all cases are seen in patients 60 and older, and 50 percent of people who live to the age of 85 will get the disease.
Griffin says that the initial screening for the study is fairly easy. "The participant will just have to answer some basic questions and fill out a health form to make sure they are relatively healthy," she said. "Additionally, we will educate them as to what to look for if they suspect they have developed zoster."
Participants will be given a varicella vaccine or placebo and will be asked to make a once-a-month phone call during the five-year study to an automated phone system that will ask basic questions such as whether the patient has developed a rash or other symptoms. Only patients who develop shingles are required to do anything further.
Study participants who develop shingles will receive the latest treatment and thorough follow up to see if the vaccine has lessened the severity of disease symptoms.
Shingles is triggered by the same varicella-zoster virus that causes chickenpox, until recently an almost universal rite of passage for American children. After a person recovers from chickenpox, the virus doesn¹t disappear. Instead it migrates up nerves from the skin and hides out in clusters of nerve cells called sensory ganglia located next to the spinal cord. The virus lays dormant until advancing age, stress, or an underlying health condition allows it to reemerge and inflame nerve fibers.
Griffin says that the first sign of the disease for elderly patients is a period of pain or itching that the patient may not understand, and then a rash of small fluid filled blisters develops at the skin¹s surface. "Often the itching and pain have been going on for several days before the patient comes in," she said. "If the rash is on a patient¹s back it may not be seen when it breaks out."
While shingles is not always a serious disease, patients often complain of pain, sometimes severe, lasting for months or even years after an outbreak. This pain is caused by inflammation of the peripheral nerve fibers involved. Pain lasting longer than one month is called post-herpetic neuralgia and occurs in about half of the patients over the age of 60 who develop shingles.
"The whole hypothesis of the study is that the vaccine will prevent post-herpetic neuralgia. Of course we hope that the vaccine will prevent all shingles, and there is some preliminary evidence that if you do get shingles the symptoms will be mild," Griffen said.
According to Wright all the evidence so far indicates that the vaccine works by boosting cell-mediated immunity for recipients.
"This is a very safe vaccine. It¹s actually the same vaccine given to children to prevent chickenpox, only in a higher dose for adults," Wright said. "We give this vaccine to children who have had no exposure to the virus. We¹ll be giving it to adults with virtual certainty that they have had exposure to chickenpox before."
"After the initial exposure to the herpes zoster virus as a child immunity is quite high. As we age there is evidence that our immunity wanes and this parallels the increasing incidence of shingles in older adults," he said.
Griffin says that any of the study participants who develop a rash will be instructed to call a twenty-four hour hotline and will receive consultation as to the likelihood of having shingles. "We¹ll ask them to come in or go visit them and take blood samples to try and confirm shingles," she said. "If we think the patient has shingles we will do serial blood samples and begin treatment with antiviral medication."
Out of the 1800 Vanderbilt study participants Griffin says that somewhere in the neighborhood of 20 to 30 patients may develop shingles during the study period.
Normally patients who develop shingles are treated with drugs that help lessen the severity and duration of the disease. "Patients are typically treated with antiviral medications such as acyclovir or famvir. These drugs have been shown to make shingles a little less painful, but they have not shown the ability to prevent post-herpetic neuralgia," she said.
Griffin says that in order for these medications to benefit shingles patients they need to be administered within the first 72 hours of onset of the rash.
"Another advantage of being in this study is that we anticipate patients to be diagnosed much faster than usual; we will counsel them on what to do; and they will be provided with famciclovir as a treatment," she said. "Early detection, treatment, and follow-up is a major part of the study."
Shingles can affect people of all ages, not just the elderly. Patients who are immunocompromised are also at risk for the disease. Griffin says that people who have the disease before the age of 40 tend not to develop post-herpetic neuralgia.
"The incidence of post-herpetic neuralgia rises dramatically with age. Some people may experience pain for a couple of months, and in a small population of people the pain can last greater than a year. In some cases the disease can be completely disabling. That¹s what the vaccine is really hoping to prevent," she said.
"Sometimes the pain associated with shingles is so severe patients stop eating and may become dehydrated. Others are unable to wear clothing because of the pain associated with post-herpetic neuralgia. The chronic pain may lead to social isolation and depression in some patients. We¹ve had to hospitalize patients for pain control. It can take weeks to get over the acute phase."
"The good news about shingles is that like chickenpox, once someone has had the disease, unless he or she is severely immunocompromised, he or she is usually immune for life."
For more information about the study, or for details on how to enroll, contact vaccine trial coordinator Cherie Robbins at 343-8800.