Immune Response to the Consumption of Lactobacillus GG and FOS in Patients With Recurrent Herpes Labialis (EVIM)

October 6, 2017 updated by: Sprim Advanced Life Sciences

A Randomized, Triple-blind Placebo-controlled Single Center Trial to Evaluate the Immune Response to the Consumption of a Minidrink Containing a Combination of Lactobacillus GG and Fructooligosaccharides in Patients With Recurrent Herpes Labialis

Background: Herpes labialis is the result of the presence of Herplex Simplex Virus -1 (HSV-1) and is a common disease in the population. Because of its visibility it has a serious impact on social life and the feeling of well-being in people who suffer from this disease. Until now there is no effective treatment and no remedy for prevention of the virus outbreak.

Prebiotics and probiotics have both been shown to have a favorable and supportive effect on the immune system in different health conditions such as influenza, atopic dermatitis and diarrhea. So far no study has addressed the effect of the consumption of pre- and/or probiotics in a population with recurrent herpes labialis.

Aim of the study: The present study investigated the effect of pre- or probiotics or a combination of the two on the recurrence of herpes labialis lesions as well as on the immune system in general.

Design: 78 Patients were eligible to participate in the study and after a run-in period of two weeks consuming a placebo minidrink were randomized to one of the four experimental groups, these were: placebo minidrink (n=), prebiotic (fructooligosaccharides) minidrink (n=), probiotic (Lactobacillus rhamnosus GG or LGG) minidrink (n=) or a minidrink containing a combination of a pre- and probiotic. These minidrinks were consumed for another 5 weeks. At day 33 of the study the lip most prone to the development of a lesion was stimulated with UVB in order to provoke a lesion. During the entire study period subjects were checked for any clinical signs of a lesion, completed a self-assessment regarding the lesion and a quality of life questionnaire at baseline (day 14) and the end of the study (day 49). In addition, a blood sample was collected at baseline and at the end of the study to be analyzed for general and HSV-specific antibodies, intracellular cytokine concentrations and parameters of the innate immune response such as natural killer cell activity and phagocytosis.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The present study showed that the daily consumption of a minidrink containing either only Lactobacillus rhamnosus or a combination of Lactobacillus rhamnosus and fructooligosaccharides significantly decreased both the occurrence and the incidence of Herpes labialis lesions after stimulation with UVR in a population with recurrent Herpes labialis. No difference in the function of either CD8+ T lymphocytes or natural killer cells was found, nevertheless a trend, that did not reach statistical significance, was observed for some of the immunological analyses pointing out towards an immunemodulating effect of probiotic or pre- and probiotic combination minidrink on the adaptive immune system. The end of study results of immune analyses were slightly improved compared to the baseline values in individuals using the probiotics or the pre- and probiotics combination minidrink, however the differences between groups did not reach the significance level. Phagocytosis and killing were clearly and statistically different in individuals that used either placebo or probiotics or pre- and probiotics minidrinks. Therefore, the probiotics and the pre- and probiotics minidrinks have an important effect on innate immunity, resulting in a significant improvement of both phagocytosis and killing. No effect was found on the quality of life of subjects. No special or unusual features of the safety evaluations were found. No serious adverse events were reported during the study.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
78

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 61 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Healthy free-living men and women aged 18 to 65 years-old
  • History of recurrent herpes labialis at most 3 episodes after exposure to sunlight in the previous 12 months
  • Fitzpatrick skin type 1 to 4
  • No presence of herpes labialis lesion at the time of recruitment
  • Consent to the study and to comply with study product
  • Agreement to adhere to the prescribed list of food and nutrients as provided at the start of the study

Exclusion Criteria:

  • Presence of acute/terminal disease
  • Intolerance for milk protein or lactose
  • Daily consumption of probiotic products 1 month before start of the study
  • Treatment with acyclovir or other medication believed to interfere with immune responses at the time of the study
  • Participation in any herpes UVB reactivation study within the previous three months
  • Episode of herpes labialis within 30 days before enrolment in the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: placebo drink
The placebo drink consists of fermented low-fat milk with no added Lactobacillus GG.(placebo)
Dietary supplement: Placebo
Active Comparator: LGG Drink (
The probiotic drink consists of fermented low-fat milk with added Lactobacillus GG. (probiotics)
Dietary supplement: Probiotics
Active Comparator: FOS Drink
The prebiotics drink consists of fermented low-fat milk with fructooligosaccharides. (prebiotics)
Dietary supplement: Prebiotics
Active Comparator: LGG e FOS Drink
The probiotics and prebiotics drink consists of acidified low-fat milk with added Lactobacillus GG and fructooligosaccharides (prebiotics and probiotics)
Dietary supplement: Prebiotics and Probiotics

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Incidence rate of ultraviolet exposure-lesion
Time Frame: Day 42
Incidence rate of ultraviolet exposure-lesion at at Day 42.
Day 42

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Incidence rate of ultraviolet exposure-lesion
Time Frame: day 35
Incidence rate of ultraviolet exposure-lesion at at Day 35.
day 35
Incidence rate of ultraviolet exposure-lesion
Time Frame: day 49
Incidence rate of ultraviolet exposure-lesion at at Day 49
day 49
Measurement of lesion size (mm2).
Time Frame: Day 35 day 42 Day 49
Measurement of lesion size as a product of the length and the width of the lesion (measured in mm2) at Day 35 / 42 / 49.
Day 35 day 42 Day 49
Time to healing (days).
Time Frame: Day 35 day 42 Day 49
Time to healing defined as either loss of the hard crust or return to normal skin (measured in days) at Day 35 / 42 / 49
Day 35 day 42 Day 49
Lesion development by classification of lesion stage.
Time Frame: Day 35 day 42 Day 49
Lesion development by classification of lesion stage. The lesion stages are shown in table 2 of the clinical protocol (adapted from Spruance et al, 2002). In addition, a photo was made at every visit. At Day 35 / 42 / 49
Day 35 day 42 Day 49
Duration and intensity of pain (10 cm Vas Analogue Scale).
Time Frame: Day 35 day 42 Day 49
Duration and intensity of pain as recorded by the patient on a visual analogue scale (VAS) of 100 mm, at Day 35 / 42 / 49.
Day 35 day 42 Day 49
Change in HSV-specific IgG, IgG3, IgG4 and IgE concentrations
Time Frame: Day 49
HSV-specific IgG1 and IgG3 (Th1) and IgG4 and IgE (Th2) concentrations were analyzed by ELISA at day 49.
Day 49
Change in HSV-specific CD8+ T cells by pentamers
Time Frame: Day 49
Immunologic evaluation of HSV-specific CD8+ T cells by pentamers (only on HLA A2-01+ individuals: an estimated 35-40% of individuals fit this criterion) at day 49.
Day 49
Change in HSV-specific CD8+ T cells by IFN-gamma ELISPOT
Time Frame: day 49
Immunologic evaluation of HSV-specific CD8+ T cells by IFN-gamma ELISPOT (only on HLA A2-01+ individuals: an estimated 35-40% of individuals fit this criterion) at day 49.
day 49
Change in lytic ability of CD8+ T cells
Time Frame: day 49
Immunologic evaluation of the lytic ability of CD8+ T cells by FACS analyses (perforin, granzymes) (all individuals).
day 49
Change in IL-2, IFN-γ, IL10
Time Frame: day 49

The following intracellular cytokine concentrations in HSV-stimulated CD4+ cells at day 49:

  • Interleukin-2;
  • Interferon-γ;
  • Interleukin-10.
day 49
Change in SF-36 QoL questionnaire.
Time Frame: day 49
The quality of life was determined by the SF-36 quality of life questionnaire at day 49.
day 49
Change in Phagocyte number and activity
Time Frame: day 49
Phagocyte number and activity as measured by flow cytometry;
day 49
Change in NK cell number and activity
Time Frame: day 49
Natural killer cell number and activity as measured by flow cytometry.
day 49

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Sprim Advanced Life Sciences

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 15, 2008

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 16, 2009

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 20, 2009

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 3, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 6, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 12, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 12, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 6, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 08-SBUS-2-GRA-01 A

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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