A Randomized Double-Blind Control-Comparison Crossover Trial of Oral Glutamine to Suppress Frequently Recurrent Herpes Labialis
Condition: Herpes Labialis; Herpes Simplex Virus
MeSH terms: Herpes Simplex; Herpes Labialis
Intervention: Glutamine; Glycine
Intervention description: Subjects were randomized to take one of the study agents, 15 gm by mouth twice daily for 5 months. After a 2 week washout period, subjects began the other agent at 15 gm by mouth twice daily for 5 months.; Subjects were randomized to take one of the study agents, 15 gm by mouth twice daily for 5 months. After a 2 week washout period, subjects began the other agent at 15 gm by mouth twice daily for 5 months.
Intervention MeSH terms: Glycine
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 11.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Glutamine; Herpes Labialis; Herpes Simplex Virus; Cold Sore

Summary:

      Background:

        -  A cold sore is usually a blistering rash on or near the lips, caused by infection with
           herpes simplex virus. After the first infection, the virus goes into a dormant
           (inactive) state, but it can continue to cause cold sores.

        -  Most people with the herpes simplex virus have a few episodes of cold sores per year.
           However, some individuals may have many recurrent episodes that are uncomfortable and
           may cause embarrassment. Researchers are attempting to find treatments that can decrease
           the number of cold sore episodes for people who have six or more episodes per year.

        -  Glutamine is a molecule called an amino acid and is one of the components that make up
           proteins in the body. Clinical studies using glutamine have addressed the potential of
           glutamine to improve immune function and to heal damaged tissue or to help healing.

      Objectives:

      - To find out if the dietary supplement glutamine can help individuals with frequently
      recurring (more than six episodes per year) cold sores.

      Eligibility:

        -  Patients between 18 and 65 years of age who have a history of having six or more cold
           sore episodes per year, and have not received certain kinds of drug treatment for the
           cold sores within 1 month of beginning the study.

        -  Patients who have two or more episodes of cold sores caused by the herpes simplex virus
           will be eligible for treatment as part of this study.

      Design:

        -  Initial clinical visit for a physical examination and medical history, at which blood
           samples will be drawn for testing.

        -  Eligible participants will undergo a 4-month screening period. Patients who develop
           sores during this period will visit the NIH to have the sore examined to determine if it
           is caused by the herpes virus. Patients who have two or more episodes of cold sores
           caused by the herpes simplex virus will be eligible for treatment.

        -  Patients who are eligible for treatment will provide an initial blood sample and will
           receive randomized doses of either glutamine or glycine (another amino acid), which must
           be taken on a regular schedule twice daily, mixed with either liquid or soft food.
           Patients who develop sores during this period will visit the NIH to have the sore
           examined to determine if it is caused by the herpes virus. Blood, urine, and saliva
           specimens will be collected each month during the treatment period. A 2-week washout
           period will occur between the 2 treatment periods when no doses of glutamine or glycine
           will be taken.

        -  Patients will then undergo a second 5-month treatment period with either glutamine or
           glycine (whichever was not given in the first part of the study), taken in the same
           manner as before. Patients who develop sores during this period will visit the NIH to
           have the sore examined to determine if it is caused by the herpes virus.

        -  After the second treatment, patients will remain in touch with researchers for 1 month
           to note any changes.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

               1. Adults, ages 18 to 65, who report a history of 6 or more episodes of herpes
                  labialis per year.

               2. Subject agrees to refrain from using over the counter (OTC), prescription or
                  supplemental antiviral medications without obtaining permission from the study
                  team during the course of the study.

               3. Women with child-bearing potential are required and willing to practice two
                  effective methods of birth control beginning with the first treatment period and
                  continuing until the end of the study.

               4. Women with child-bearing potential are required to have a negative pregnancy test
                  at the time of enrollment and at the time of randomization.

               5. To be eligible for randomization in the treatment phase of the study, the
                  participants must experience at least 2 clinically confirmed episodes of herpes
                  labialis, 1 of which must be virologically confirmed, during the 4 month
                  screening period.

        EXCLUSION CRITERIA:

          1. Oral or intravenous antiviral therapy < 4 weeks before enrollment or during the study
             with the following agents is not permitted: acyclovir (intravenous), ganciclovir
             (intravenous or oral), valganiciclovir (oral), cidofovir (intravenous), or foscarnet
             (intravenous).

               1. Suppressive therapy with oral acyclovir, valacyclovir or famciclovir or with
                  topical antivirals 4 weeks prior to enrollment or during the study is not
                  permitted.

               2. Use of oral acyclovir or valacyclovir or famciclovir or topical antiviral
                  ointments or creams for the treatment of herpes labialis outbreaks during the
                  study is permitted AFTER the outbreak has been documented by the study team..

          2. Evidence of active herpes labialis reactivation at the time of enrollment. The
             volunteer can be enrolled after resolution of herpes labialis and if inclusion and
             exclusion criteria are still met.

          3. Subjects with conditions associated with immunodeficiency (e.g., human
             immunodeficiency virus infection) or conditions requiring either daily systemic
             corticosteroids exceeding a dose equivalent to10 mg/day of prednisone or other
             significant immunosuppressant therapy (e.g., organ or stem cell transplantation).

          4. Persons with significant liver or kidney disease [serum glutamic oxaloacetic
             transaminase [SGOT], serum glutamine pyruvic transaminase [SGPT], or alkaline
             phosphatase > 2.5 times the upper limit of normal (ULN), total bilirubin > 1.5 times
             the ULN, or serum creatinine > 1.5 times the ULN].

          5. Persons with an active seizure disorder. For persons with prior history of seizures,
             the person should be seizure free for 5 years and not on any anti-seizure medication
             in order to be enrolled into the study. (Since glutamine is metabolized to glutamate
             and ammonia, and glutamate is the main excitatory neurotransmitter in the central
             nervous system (CNS), there is a theoretical increased risk of seizures).

          6. Women who are known to be pregnant (pregnancy category C) or breastfeeding (it is not
             known whether glutamine is excreted in human milk).

          7. History of allergic reaction to glutamine or glutamic acid or their derivatives (e.g.,
             monosodium glutamate) or to glycine or sucralose.

          8. Subjects cannot take supplemental amino acids (e.g., glutamine, glycine, arginine,
             other amino acids) or high protein supplements, such as Boost within 30 days of
             enrollment into the study or during the study (except for study drug amino acid).
             Subjects can take vitamins.

          9. Persons treated with atypical neuroleptics such as clozapine (Clozaril, FazoCIo) or
             olanzapine (Zyprexa, Zydis).

         10. Participation in any study involving investigational drugs within 30 days prior to
             entry into this trial.

         11. Any condition (e.g., schizophrenia, psychosis, major depression, mental deficiency or
             illness) or major co-morbidity that the study investigator thinks might compromise the
             person's ability to comply with the requirements of the study.