Herpes LabialisEVIMNCT03307772
Immune Response to the Consumption of Lactobacillus GG and FOS in Patients With Recurrent Herpes Labialis
A study testing Probiotics, Prebiotics and Prebiotics and Probiotics in people with Herpes Labialis, run by Sprim Advanced Life Sciences.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Herpes Labialis
- What is being tested?
- Probiotics, Prebiotics and Prebiotics and Probiotics
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 78 participants
- Where
- No sites listed yet
- Study dates
- 15 Dec 2008to 20 Oct 2009
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
About this study
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
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.
Read more
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.
Read the 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.
- Conditions
- Herpes Labialis
- Being tested
- Probiotics, Prebiotics, Prebiotics and Probiotics, Placebo
- Keywords
- lactobacillus, Herpes Labialis, immune response
- Medical subject headings
- Herpes Labialis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ProbioticsDietary supplement
PrebioticsDietary supplement
Prebiotics and ProbioticsDietary supplement
PlaceboDietary supplement
| Study group | Role | What they receive |
|---|---|---|
| placebo drink | Placebo comparator | The placebo drink consists of fermented low-fat milk with no added Lactobacillus GG.(placebo) Receives: Dietary Supplement: Placebo |
| LGG Drink ( | Active comparator | The probiotic drink consists of fermented low-fat milk with added Lactobacillus GG. (probiotics) Receives: Dietary Supplement: Probiotics |
| FOS Drink | Active comparator | The prebiotics drink consists of fermented low-fat milk with fructooligosaccharides. (prebiotics) Receives: Dietary Supplement: Prebiotics |
| LGG e FOS Drink | Active comparator | The probiotics and prebiotics drink consists of acidified low-fat milk with added Lactobacillus GG and fructooligosaccharides (prebiotics and probiotics) Receives: Dietary Supplement: Prebiotics and Probiotics |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence rate of ultraviolet exposure-lesion
Incidence rate of ultraviolet exposure-lesion at at Day 42.
Measured: Day 42
Secondary outcomes (14)
Incidence rate of ultraviolet exposure-lesion
Incidence rate of ultraviolet exposure-lesion at at Day 35.
Measured: day 35
Incidence rate of ultraviolet exposure-lesion
Incidence rate of ultraviolet exposure-lesion at at Day 49
Measured: day 49
Measurement of lesion size (mm2).
Measurement of lesion size as a product of the length and the width of the lesion (measured in mm2) at Day 35 / 42 / 49.
Measured: Day 35 day 42 Day 49
Time to healing (days).
Time to healing defined as either loss of the hard crust or return to normal skin (measured in days) at Day 35 / 42 / 49
Measured: Day 35 day 42 Day 49
Lesion development by classification of lesion stage.
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
Measured: Day 35 day 42 Day 49
Duration and intensity of pain (10 cm Vas Analogue Scale).
Duration and intensity of pain as recorded by the patient on a visual analogue scale (VAS) of 100 mm, at Day 35 / 42 / 49.
Measured: Day 35 day 42 Day 49
Change in HSV-specific IgG, IgG3, IgG4 and IgE concentrations
HSV-specific IgG1 and IgG3 (Th1) and IgG4 and IgE (Th2) concentrations were analyzed by ELISA at day 49.
Measured: Day 49
Change in HSV-specific CD8+ T cells by pentamers
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.
Measured: Day 49
Change in HSV-specific CD8+ T cells by IFN-gamma ELISPOT
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.
Measured: day 49
Change in lytic ability of CD8+ T cells
Immunologic evaluation of the lytic ability of CD8+ T cells by FACS analyses (perforin, granzymes) (all individuals).
Measured: day 49
Change in IL-2, IFN-γ, IL10
The following intracellular cytokine concentrations in HSV-stimulated CD4+ cells at day 49:
- Interleukin-2;
- Interferon-γ;
- Interleukin-10.
Measured: day 49
Change in SF-36 QoL questionnaire.
The quality of life was determined by the SF-36 quality of life questionnaire at day 49.
Measured: day 49
Change in Phagocyte number and activity
Phagocyte number and activity as measured by flow cytometry;
Measured: day 49
Change in NK cell number and activity
Natural killer cell number and activity as measured by flow cytometry.
Measured: day 49
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Oct 2017
- Study start15 Dec 2008
- Primary completion16 Sep 2009
- Study completion20 Oct 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Herpes LabialisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 78 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sprim Advanced Life Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03307772
- Sponsor's protocol ID
- 08-SBUS-2-GRA-01 A
- Acronym
- EVIM
- Status last verified
- Oct 2017
- First submitted
- 3 Oct 2017
- Last updated
- 12 Oct 2017
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03307772
- Acronym / sponsor ID
- EVIM / 08-SBUS-2-GRA-01 A
- Conditions
- Herpes Labialis
- Keywords
- lactobacillus, Herpes Labialis, immune response
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 78 participants (actual)
- Lead sponsor
- Sprim Advanced Life SciencesUniversity, hospital or other
- Study start
- 15 Dec 2008 (actual)
- Primary completion
- 16 Sep 2009 (actual)
- Study completion
- 20 Oct 2009 (actual)
- First posted
- 12 Oct 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| placebo drink | Placebo comparator | Dietary Supplement: PlaceboThe placebo drink consists of fermented low-fat milk with no added Lactobacillus GG.(placebo) |
| LGG Drink ( | Active comparator | Dietary Supplement: ProbioticsThe probiotic drink consists of fermented low-fat milk with added Lactobacillus GG. (probiotics) |
| FOS Drink | Active comparator | Dietary Supplement: PrebioticsThe prebiotics drink consists of fermented low-fat milk with fructooligosaccharides. (prebiotics) |
| LGG e FOS Drink | Active comparator | Dietary Supplement: Prebiotics and ProbioticsThe probiotics and prebiotics drink consists of acidified low-fat milk with added Lactobacillus GG and fructooligosaccharides (prebiotics and probiotics) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Probiotics | Dietary supplement | LGG Drink ( |
| Prebiotics | Dietary supplement | FOS Drink |
| Prebiotics and Probiotics | Dietary supplement | LGG e FOS Drink |
| Placebo | Dietary supplement | placebo drink |
Primary outcome
Incidence rate of ultraviolet exposure-lesion
Time frame: Day 42
Incidence rate of ultraviolet exposure-lesion at at Day 42.
14 secondary outcomes
Incidence rate of ultraviolet exposure-lesion
Time frame: day 35
Incidence rate of ultraviolet exposure-lesion
Time frame: day 49
Measurement of lesion size (mm2).
Time frame: Day 35 day 42 Day 49
Time to healing (days).
Time frame: Day 35 day 42 Day 49
Lesion development by classification of lesion stage.
Time frame: Day 35 day 42 Day 49
Duration and intensity of pain (10 cm Vas Analogue Scale).
Time frame: Day 35 day 42 Day 49
Change in HSV-specific IgG, IgG3, IgG4 and IgE concentrations
Time frame: Day 49
Change in HSV-specific CD8+ T cells by pentamers
Time frame: Day 49
Change in HSV-specific CD8+ T cells by IFN-gamma ELISPOT
Time frame: day 49
Change in lytic ability of CD8+ T cells
Time frame: day 49
Change in IL-2, IFN-γ, IL10
Time frame: day 49
Change in SF-36 QoL questionnaire.
Time frame: day 49
Change in Phagocyte number and activity
Time frame: day 49
Change in NK cell number and activity
Time frame: day 49
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A study testing Probiotics, Prebiotics and Prebiotics and Probiotics in people with Herpes Labialis, run by Sprim Advanced Life Sciences.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence rate of ultraviolet exposure-lesion (time frame: Day 42). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Oct 2017.