The purpose of this study is to see if giving Valacyclovir (VACV) to patients with herpes simplex encephalitis (HSE) can increase the survival rates of these patients and reduce brain and nervous system damage. A sub-study will also be performed to look at the relationship between the level of herpes virus in the blood and "long-term" brain damage injury caused by the HSE infection.

Condition	Treatment or Intervention	Phase
Encephalitis, Herpes Simplex	Drug: Valacyclovir hydrochloride	Phase III

Further Study Details: 

Expected Total Enrollment:  132

There are currently two main types of herpes that are known to lead to HSE. These viruses are spread by intimate contact and/or contact with body fluids such as saliva, blood, breast milk, or semen. People who have herpes do not always have symptoms as the herpes virus may lay dormant in the body for long periods of time. Those who become symptomatic will have a variety of symptoms such as fever, mouth sores, or genital sores that may then spread into the central nervous system. If the virus penetrates the central nervous system and enters into the spinal fluid, it may cause headache, fever, myalgia, difficulty with speech, seizures, and, if left untreated, can lead to brain damage, coma and even death. An infection of this nature cause by herpes simplex is referred to as herpes simplex encephalitis (HSE). HSE is currently treated with a drug called acyclovir (ACV). However, 20% of patients die of this disease and 60% have long-term brain damage, even if they receive ACV. Hospitalization for IV ACV therapy can only be anticipated for a finite time, usually 14-21 days. Thus, a bioavailable drug capable of achieving plasma levels similar to IV ACV would be beneficial. This study tests the therapeutic effect of adding the drug valacyclovir (VACV), the oral pro-drug of ACV, to the current treatment with ACV. The sub-study will look at the areas of the brain that are affected by HSE to determine if early and long-term treatment with VACV is beneficial.

Ages Eligible for Study:  12 Years and above,  Genders Eligible for Study:  Both

Criteria

INCLUSION CRITERIA:

• You may be eligible for this study if you: are 12 years of age or older (parental/guardian consent required if under 18); weigh at least 100 pounds;have HSE (a test of your cerebrospinal fluid must be positive for herpes simplex virus); have completed IV ACV therapy for a minimum of 14 days to a maximum of 21 days and a minimum dose of 30mg per kg per day to a maximum of 60mg per kg per day; available for follow-up visits at least for 90-days of study drug administration; agree to practice abstinence or use effective birth control while you are taking the study medication and for 30 days after finishing study medication. Informed consent or assent must be obtained from the patient or legal guardian.

EXCLUSION CRITERIA:

• The following conditions exclude participation in this trial: Failure to detect HSV DNA in the patient's CSF by PCR; creatinine clearance less than or equal to 50 ml/min/1.73 m (sq); have a life expectancy of less than 90 days; are unable to swallow oral medications; are more than 3 days beyond completion of IV ACV therapy; are not receiving or will not have completed IV ACV therapy for a minimum of 14 days to a maximum of 21 days and a minimum dose of 30 mg/kg/day to a maximum of 60 mg/kg/day; have received any anti-herpes virus medications other than ACV to treat the current episode of HSE; expected to receive long-term (more than 30 days) therapy with antiviral medications active against HSV; are pregnant or continue to breast-feed; refuse to sign an informed consent.

Laura Riser      1-877-975-7280    LRiser@peds.uab.edu

Alabama
      University of Alabama at Birmingham (CASG), Birmingham,  Alabama,  35294,  United States; Recruiting
California
      University of Southern California, Los Angeles,  California,  90033,  United States; Recruiting
Colorado
      Denver VA Medical Center, Denver,  Colorado,  80220,  United States; Recruiting
Indiana
      Indiana University, Indianapolis,  Indiana,  46202,  United States; Recruiting
Kansas
      University of Kansas, Kansas City,  Kansas,  66160,  United States; Recruiting
      Via Christi Regional Medical Center, Wichita,  Kansas,  67214,  United States; Recruiting
      Kansas City Cancer Centers, Kansas City,  Kansas,  66112,  United States; Recruiting
Maryland
      Johns Hopkins University, Baltimore,  Maryland,  21287,  United States; Recruiting
Minnesota
      Mayo Clinic - Rochester MN, Rochester,  Minnesota,  55905,  United States; Recruiting
Missouri
      St. Louis University, St. Louis,  Missouri,  63104,  United States; Recruiting
New Mexico
      University of New Mexico - Albuquerque, Albuquerque,  New Mexico,  87106,  United States; Recruiting
New York
      Columbia University, New York Presbyterian Hospital, New York,  New York,  10032,  United States; Recruiting
      State University of New York at Stony Brook, Stony Brook,  New York,  11794,  United States; Recruiting
Pennsylvania
      Thomas Jefferson University, Philadelphia,  Pennsylvania,  19107,  United States; Recruiting
Texas
      University of Texas - Houston, Houston,  Texas,  77030,  United States; Recruiting
Virginia
      University of Virginia, Charlottesville,  Virginia,  22904,  United States; Recruiting
Canada, Alberta
      University of Alberta, Edmonton,  Alberta,  T6G2B7,  Canada; Recruiting
Canada, Manitoba
      University of Manitoba, Winnipeg,  Manitoba,  R3EOW3,  Canada; Recruiting
Canada, Ontario
      Kingston General Hospital, Kingston,  Ontario,  K7L2V7,  Canada; Recruiting
Sweden
      Karolinska University, Stockholm,  Sweden; Recruiting
      Lund University, Lund,  Sweden; Recruiting
      Gothenberg University, Gothenberg,  Sweden; Recruiting
      Uppsala University Medical School, Uppsala,  Sweden; Recruiting
      Umea University, Umea,  Sweden; Recruiting
United Kingdom
      Royal Free & Univ. College Medical School, London,  NW32PF,  United Kingdom; Recruiting

Study ID Numbers:  98-022
Record last reviewed:  December 2003
Last Updated:  December 29, 2004
Record first received:  March 6, 2002
ClinicalTrials.gov Identifier:  NCT00031486
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08