Protocol Number: 09-I-0159

Title:

A Randomized Double-Blind Control-Comparison Crossover Trial of Oral Glutamine to Suppress Frequently Recurrent Herpes Labialis

Number:

09-I-0159

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.

Sponsoring Institute:

National Institute of Allergy and Infectious Diseases (NIAID)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

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. 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.

3. Women with child-bearing potential are required to have a negative pregnancy test at the time of enrollment and at the time of randomization.

4. 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 (acyclovir, famciclovir, valacyclovir, ganciclovir, valganciclovir, cidofovir, foscarnet) < 4 weeks before enrollment into the study or during the study. Use of topical antiviral creams or ointments < 4 weeks prior to enrollment is permitted.

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 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 who have other frequently recurrent oral and perioral lesions, such as aphthous ulcers or cheilitis, that are likely to be mistakenly diagnosed as having recurrent herpes simplex virus infection.

9. 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.

10. Persons treated with atypical neuroleptics such as clozapine (Clozaril, FazoCIo) or olanzapine (Zyprexa, Zydis).

11. Participation in any study involving investigational drugs within 30 days prior to entry into this trial.

12. 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.

Special Instructions:

Currently Not Provided

Keywords:

Glutamine

Herpes Labialis

Herpes Simplex Virus

Cold Sore

Recruitment Keyword(s):

Herpes Simplex Virus

Cold Sore

Condition(s):

Herpes Labialis

Herpes Simplex Virus

Investigational Drug(s):

Glautamine and Glycine

Investigational Device(s):

None

Intervention(s):

Drug: Glutamine

Drug: Glycine

Supporting Site:

National Institute of Allergy and Infectious Diseases

Contact(s):

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citation(s):

Anderson PM, Ramsay NK, Shu XO, Rydholm N, Rogosheske J, Nicklow R, Weisdorf DJ, Skubitz KM. Effect of low-dose oral glutamine on painful stomatitis during bone marrow transplantation. Bone Marrow Transplant. 1998 Aug;22(4):339-44

Aquino VM, Harvey AR, Garvin JH, Godder KT, Nieder ML, Adams RH, Jackson GB, Sandler ES. A double-blind randomized placebo-controlled study of oral glutamine in the prevention of mucositis in children undergoing hematopoietic stem cell transplantation: a pediatric blood and marrow transplant consortium study. Bone Marrow Transplant. 2005 Oct;36(7):611-6.

Baker D, Eisen D. Valacyclovir for prevention of recurrent herpes labialis: 2 double-blind,placebo-controlled studies. Cutis. 2003 Mar;71(3):239-42.

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