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

NCT00913692 | Terminated Phase 2 Results DMC

• 2 other identifiers: 09015909-I-0159
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Herpes Labialis; Herpes Simplex Virus

Keywords

Glutamine; Herpes Labialis; Herpes Simplex Virus; Cold Sore

Outcome Measures

Primary Outcomes (1)

• Does Oral Glutamine Reduce the Number of Recurrences of Herpes Labialis, Diagnosed by Clinical and Microbiologic Criteria, in Healthy Participants With Frequently Recurrent Disease.

  During all phases of the study, participants returned to clinic whenever they had a herpes labialis outbreak for staff to assess, obtain a viral swab and document. If unable to return to clinic in the time frame specified in the protocol, participants would take a photo and obtain a swab of the lesion. The number of outbreaks would be measured during each phase.

  The screening phase time frame was 4 months. Treatment phase 1 was 5 months. Washout phase was 2 weeks. Treatment phase 2 was 5 months.

Secondary Outcomes (4)

• Does Oral Glutamine Reduce the Number of Clinical Recurrences of Herpes Labialis With or Without PCR Confirmation?

  The screening phase time frame was 4 months. Treatment phase 1 was 5 months. Washout phase was 2 weeks. Treatment phase 2 was 5 months.

• Does Oral Glutamine Reduce the Time to First Recurrence of Herpes Labialis Diagnosed by Clinical and Microbiologic Criteria or Diagnosed by Clinical Criteria With or Without PCR Confirmation?

  The screening phase time frame was 4 months. Treatment phase 1 was 5 months. Washout phase was 2 weeks. Treatment phase 2 was 5 months.

• Does Oral Glutamine Reduce the Duration of Recurrences?

  The screening phase time frame was 4 months. Treatment phase 1 was 5 months. Washout phase was 2 weeks. Treatment phase 2 was 5 months.

• Does Oral Glutamine Reduce the Area of Recurrent Lesions?

  The screening phase time frame was 4 months. Treatment phase 1 was 5 months. Washout phase was 2 weeks. Treatment phase 2 was 5 months.

Interventions

Glutamine DRUG

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.

Glycine DRUG

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.

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults, ages 18 to 65, who report a history of 6 or more episodes of herpes labialis per year.
• 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.
• 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.
• Women with child-bearing potential are required to have a negative pregnancy test at the time of enrollment and at the time of randomization.
• 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.

You may not qualify if:

• 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).
• Suppressive therapy with oral acyclovir, valacyclovir or famciclovir or with topical antivirals 4 weeks prior to enrollment or during the study is not permitted.
• 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..
• 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).
• 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\].
• 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).
• Women who are known to be pregnant (pregnancy category C) or breastfeeding (it is not known whether glutamine is excreted in human milk).
• History of allergic reaction to glutamine or glutamic acid or their derivatives (e.g., monosodium glutamate) or to glycine or sucralose.
• 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.
• Persons treated with atypical neuroleptics such as clozapine (Clozaril, FazoCIo) or olanzapine (Zyprexa, Zydis).
• Participation in any study involving investigational drugs within 30 days prior to entry into this trial.
• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• 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. doi: 10.1038/sj.bmt.1701317.

  PMID: 9722068 BACKGROUND

• 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. doi: 10.1038/sj.bmt.1705084.

  PMID: 16086046 BACKGROUND

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

  PMID: 12661753 BACKGROUND

MeSH Terms

Conditions

Herpes Labialis; Herpes Simplex

Interventions

Glutamine; Glycine

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Skin Diseases, Viral; Lip Diseases; Mouth Diseases; Stomatognathic Diseases; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Neutral

Limitations and Caveats

The protocol was terminated early due to slow recruitment.

Results Point of Contact

• Title: Jeffrey I. Cohen, MD
• Organization: National Institute of Allergy and Infectious Diseases, Laboratory of Infectious Diseases

jcohen@niaid.nih.gov

(301) 496-5265

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 3, 2009
• First Posted: June 4, 2009
• Study Start: June 1, 2009
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: June 11, 2012
• Results First Posted: June 11, 2012

Record last verified: 2012-05

Locations

US (1)