Immune Evidence to the Consumption of Lactobacillus GG and FOS Consumption in Patients With Herpes Labialis
Condition: Herpes Labialis
MeSH terms: Herpes Simplex; Herpes Labialis
Study type: Interventional

Summary: 
      Herpes labialis (HL) is the result of the presence of a virus called HSV-1 and is a common
      disease. Because of its visibility due to cold sores it has a serious impact on social life.
      Until now there is no effective treatment to prevent virus outbreaks. However, 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
      it is possible that they are able to have a favourable effect also on HL.

      A recently completed pilot clinical trial (Protocol Number 08-SBUS-2-GRA-01, EVIM-1) was
      completed using a fermented milk (minidrink) containing a combination of L. rhamnosus and
      FOS; it showed promising results in the reduction of HL recurrences in a population of 78
      subjects with HSV-1. The study investigated the effect of pre- or probiotics or a combination
      of the two on the recurrence of HL lesions as well as on the immune system in general,
      showing that the consumption of a minidrink containing the probiotic L. rhamnosus or a
      minidrink containing a combination of L. rhamnosus and FOS reduced the occurrence and the
      incidence of recurrent HL lesions.

      Aim of this study: corroborate whether the consumption of a minidrink containing a
      combination of L. rhamnosus and FOS results in less recurrence and a better progression of HL
      lesion, in a larger population. In addition, the response of the consumption of the minidrink
      on the QoL and the response on immunity specific biomarkers were evaluated.

      Design: 152 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 two experimental study
      groups: placebo minidrink (n=79) and a minidrink containing a combination of a pre- and
      probiotic (n=78). These minidrinks were consumed until the end of the study (day 140). At day
      33 of the study the lip most prone to the development of a lesion was stimulated with UVB 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 QoL questionnaire at
      baseline (day 14), at day 49 and the end of the study (day 140). In addition, a blood sample
      was collected at baseline, at day 49 and at the end of the study to be analyzed for
      HSV-specific antibody concentrations , to check immune system specific functions.
    

Detailed description: 
      Background: Herpes labialis is the result of the presence of HSV-1 and is a common disease.
      Because of its visibility it has a serious impact on social life. Until now there is no
      effective treatment to prevent virus outbreaks. However, 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.

      A recently completed pilot clinical trial (Protocol Number 08-SBUS-2-GRA-01, EVIM-1) parallel
      groups, placebo controlled, triple blind, single center, randomized study, with a fermented
      milk (minidrink) containing a combination of L. rhamnosus and FOS showed promising results in
      the reduction of HL recurrences in a population of 78 subjects with HSV-1; the study
      investigated the effect of pre- or probiotics or a combination of the two on the recurrence
      of HL lesions as well as on the immune system in general, showing that the consumption of a
      minidrink containing the probiotic L. rhamnosus or a minidrink containing a combination of L.
      rhamnosus and FOS reduced the occurrence and the incidence of recurrent HL lesions.

      Aim of the study: corroborate whether the consumption of a minidrink containing a combination
      of L. rhamnosus and FOS results in less recurrence and a better progression of HL lesion, in
      a larger population. In addition, the response of the consumption of the minidrink on the QoL
      and the response on immunity specific biomarkers were evaluated.

      Design: 152 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 two experimental study
      groups: placebo minidrink (n=79) and a minidrink containing a combination of a pre- and
      probiotic (n=78). These minidrinks were consumed until the end of the study (day 140). At day
      33 of the study the lip most prone to the development of a lesion was stimulated with UVB 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 QoL questionnaire at
      baseline (day 14), at day 49 and the end of the study (day 140). In addition, a blood sample
      was collected at baseline, at day 49 and at the end of the study to be analyzed for
      HSV-specific antibody concentrations (circulating concentrations of IgG1 and IgG3 (Th1) and
      IgG4 (Th2), NK activity, CXCL10 analyzed by ELISA at days 14, 49 and 140).

      as regards the primary endpoint results have shown that there was a significant decrease
      (54.3%) in the recurrences of Herpes labialis lesions, post UV stimulation, at day 49 (V4)
      compared to placebo in the PP population with consumption of the study product minidrink with
      fermented low fat milk added with Lactobacillus rhamnosus and FOS. Considering the secondary
      endpoints in the PP population, considering the number of subjects who presented lesions
      between V0 and V5, the number of lesions is reduced significantly (both statistically and
      clinically) in the treatment group compared to the placebo group. There was a decrease in the
      lesion size in the treatment group when compared to placebo although the statistical
      significance is marginal. As regards 'Subjective assessment of pain', evaluated by means of a
      VAS scale, significant pain reduction was found in the treatment group compared to the
      placebo group. As regards immunological parameters was shown an increase in CXCL10 at V4 in
      the study group compared to the placebo group. As regards IgG1, IgG3 and IgG4 (V0, V4 and V5)
      although substantial increases were registered for some of these parameters, these were not
      sufficient to describe a definite trend. The natural killer (NK) cell activity did not show
      significant difference in their functional activity in the treatment group as compared to the
      placebo group.

      It has been verified through quality of life questionnaire (SF-36 questionnaire) that
      treatment improved Mental Health in the treatment group (Nervous, Peaceful, Happy, Down in
      Dumps, Sad) compared to the placebo group and clinical significance was found at V4 and V5.
      General Health and Vitality has been improved at V4 and V5.

      For each trial participant the adverse events/serious adverse events occurrences and a brief
      clinical examination were assessed. No special or unusual features of the safety evaluations
      were found.
    

Intervention name(s): Placebo; Prebiotics and Probiotics
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): one bottle of placebo (minidrink fermented with low-fat milk but without Lactobacillus rhamnosus and without FOS, and without viable bacteria 90 grams)per day at breakfast until the end of the study (V5, day 140). At each visit, subjects were dispensed a sufficient amount of minidrinks until the next visit.; one bottle of the study product (minidrink with fermented low-fat milk added with Lactobacillus rhamnosus (Lactobacillus rhamnosus) and fructooligosaccharides (FOS),per day at breakfast until the end of the study (V5, day 140). At each visit, subjects were dispensed a sufficient amount of minidrinks until the next visit.
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This is a phase IV, parallel, placebo-controlled, double-blind, multicenter, randomized study to evaluate the effect of a combination of probiotics and prebiotics in subjects with recurrent Herpes labialis.
This specific design has been chosen as the most suitable to achieve the objectives of the trial, mainly the demonstration of the clinical efficacy of the combination of probiotics and prebiotics in subjects with recurrent Herpes labialis in terms of reduction of the number of HL recurrences at day 49 vs baseline.
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Lactobacillus; Herpes Labial; Immune repsonse