Clinical trial NCT03307772: Immune Response to the Consumption of Lactobacillus GG and FOS in Patients With Recurrent Herpes Labialis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Herpes Labialis
Keywords: lactobacillus
Herpes Labialis
immune response
Lead sponsor: Sprim Advanced Life Sciences
Sponsor class: OTHER
First posted: 2017-10-12
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence rate of ultraviolet exposure-lesion
timeFrame: Day 42
Secondary outcomes:
measure: Incidence rate of ultraviolet exposure-lesion
timeFrame: day 35
measure: Incidence rate of ultraviolet exposure-lesion
timeFrame: day 49
measure: Measurement of lesion size (mm2).
timeFrame: Day 35 day 42 Day 49
measure: Time to healing (days).
timeFrame: Day 35 day 42 Day 49
measure: Lesion development by classification of lesion stage.
timeFrame: Day 35 day 42 Day 49
measure: Duration and intensity of pain (10 cm Vas Analogue Scale).
timeFrame: Day 35 day 42 Day 49
measure: Change in HSV-specific IgG, IgG3, IgG4 and IgE concentrations
timeFrame: Day 49
measure: Change in HSV-specific CD8+ T cells by pentamers
timeFrame: Day 49
measure: Change in HSV-specific CD8+ T cells by IFN-gamma ELISPOT
timeFrame: day 49
measure: Change in lytic ability of CD8+ T cells
timeFrame: day 49
measure: Change in IL-2, IFN-γ, IL10
timeFrame: day 49
measure: Change in SF-36 QoL questionnaire.
timeFrame: day 49
measure: Change in Phagocyte number and activity
timeFrame: day 49
measure: Change in NK cell number and activity
timeFrame: day 49
Other outcomes:
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