Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04706559 |
| Other study ID # |
IRC/1886/020 |
| Secondary ID |
720/2020 MT |
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
January 3, 2021 |
| Est. completion date |
December 15, 2021 |
Study information
| Verified date |
December 2020 |
| Source |
B.P. Koirala Institute of Health Sciences |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Various clinical studies have evaluated the role of probiotics in children with atopic
dermatitis, with some studies showing improvement in clinical outcome after supplementation
of probiotics and others showing no additional benefit. This study is to provide clinical
evidence of effect of a mixture of probiotics in Atopic Dermatitis (AD) patients based on
improvement in SCORAD (SCORing Atopic Dermatitis) index.
Description:
Atopic dermatitis (AD) is the common chronic inflammatory skin disease with relapsing courses
that often start in infancy and childhood. It is characterized by erythema, itchy papules,
occasionally vesicles (in infants), which may become excoriated and lichenified and have a
typical flexural distribution. Atopy is defined as a "personal or familial tendency to
produce immunoglobulin antibodies in response to even low doses of allergen, and associated
with development of AD, asthma and rhinoconjunctivitis.The worldwide prevalence of AD is
estimated to be 20% in children and 2-10% in adults. The incidence of AD has increased by 2
to 3 folds in past 3 decades in the industrialized countries and represents a major public
health burden. According to the International Study of Asthma and Allergies in Childhood
(ISAAC) phase 3, the prevalence of AD among the age group of 13 to 14 in Africa and Latin
America was at 12-14% and 6-10% respectively. The Asian Pacific countries, the Eastern
Mediterranean region and the Indian subcontinent, it was 3-6% among the same age groups
(13-14 years). Whereas among 6 to 7 years children, for Asian Pacific countries, Africa and
Latin America the prevalence of AD was around 10% and in Indian subcontinent and Eastern
Mediterranean region, value was lower at 3-5%
In Nepal the frequency of AD in all age group was 2% as per a year hospital based study done
by Singh S and Agrawal S et.al in 2012. (Unpublished data, on personal communication)
The pathogenesis of AD appears to result from interaction between various genetic and
environmental factors. It is associated with skin barrier dysfunction and immune
dysregulation. The barrier dysfunction is early feature of AD which may be a primary but may
also be a secondary to skin inflammation. Lack of exposure to microbial stimuli in early life
programs the immune system towards Th2-type allergic response as described by 'hygiene
hypothesis'.In allergic disorders there is shift of the Th1/Th2 cytokine balance towards a
Th2 response, and causes the release of Interleukin-4, interleukin-5 and interleukin-13 as
well as Immunoglobulin E production.
The diagnosis of AD is mainly clinical as there is no specific test for AD. Diagnosis of AD
is based on specific a criterion which includes patient's history, clinical presentations as
well as family history. In 1980 Hanifin and Rajka proposed major and minor diagnostic
criteria based on clinical symptoms of AD. Williams coordinated a UK working party to attempt
to simplify and refine the criteria given by Hanifin and Rajka in 1994. Severity of disease
is evaluated by using widely accepted SCORing Atopic Dermatitis (SCORAD), based on extent of
area involved, severity of symptoms and intensity of the subjective symptoms of pruritus and
sleep disturbances.The chronic and recurrent nature of AD negatively impacts the quality of
life (QOL) of patients as well as their family members. The symptoms of AD limit patient's
physical, psychosocial development and quality of sleep.
The main goals of treatment are to improve the skin barrier function and hydration, to
suppress inflammation and to control microbial colonization. It can be achieved through
emollients, topical corticosteroids and topical calcineurin inhibitor like tacrolimus. Oral
drugs like corticosteroids, methotrexate and cyclosporine are reserved for severe cases.
Probiotics are defined by World Health Orgnization as "live microorganisms, which when
consumed in adequate amounts, confer a health effect on the host."Under the hypothesis that
probiotics have global allergy protective effect, they have been extensively used for several
conditions like inflammatory bowel disease, bronchial asthma and other allergic diseases. If
children who are genetically predisposed to AD are supplemented with probiotics early in
their life, series of events like antigenic competition, immune regulation and stimulation of
innate immunity will occur, all of which might minimize their susceptibility to allergic
disorders. Hence, investigators planned this study to see its role in AD.
Statement of problem and rationale:
The rationale for this therapeutic option is based on well-established effects of bacteria on
cellular immune responses. The probiotics has an immunomodulatory property that plays an
essential role in the development of normal immune tolerance. Early life exposure to these
microbial agents plays an important role in maturation of Type 1 helper cell (Th1) immune
responses and could inhibit development of allergic Type 2 helper cell (Th2) responses and
IgE antibody production. Therefore the onset of AD could be prevented by probiotics and this
treatment strategy could also be effective even when AD is already established.
In a meta-analysis conducted in 2017, involving 13 randomized controlled trials (RCT) with
1,070 children, significant difference in SCORAD values favoring probiotics over the control
group was observed. Though, a high degree of heterogeneity was observed across these 13
trials.
Cochrane review, 2018 which included 39 RCTs found that probiotic treatment may slightly
reduce SCORAD value. However the researcher concluded that the differences were not
clinically significant. Recent review in 2019 on "prebiotics and probiotics in atopic
dermatitis" based on various RCT and meta-analysis support the supplementation of probiotics
for at least 8 weeks in improving severity score of AD.
Investigators have observed conflicting results of different studies with some showing
significant advantages while some studies revealing no benefit. Almost all of the studies
have suggested further research in different populations. Therefore, we are conducting this
study to find out the effect of probiotics in AD in our institute.
OBJECTIVES
1. Primary objective: To investigate the efficacy of oral probiotics in the clinical
outcome of Atopic dermatitis based on the SCORAD index
2. Secondary objectives: To find out the total duration of topical corticosteroid use in
the interventional and conventional group.
To assess the impact of AD in children's family members based on FDLQI (Family Dermatology
Life Quality Index)
MATERIALS AND METHODS Type of study design: Assessor blinded, randomized controlled trial.
Setting: Hospital (Dermatology Outpatient Department, BPKIHS, Dharan). The probable duration
of the study will be one year after approval from the Institutional Review Committee and
Nepal Health Research Council (NHRC). Ethical Clearance: taken from the Institutional Review
Committee (IRC), BPKIHS, and Nepal Health Research Council (NHRC).
Calculation of the sample size: According to a study done by Ekaputri et.al, it is reported
that mean± SD of SCORAD index after intervention in probiotic group and control group was
(18.09 ± 8.59) and (23.21± 8.71) respectively. Considering the least difference, 5.12 and
pooled SD- 8.65, the sample size has been calculated at 95% CI and 80% power, using two means
formula.
n = 44.56, adding 10% in calculated value for lost to follow-up, final sample size is 45 in
each group. Thus a total of 98 patients will be enrolled.
n = 2σ2 (Z α/2 + Z β) 2 (μ1- μ2) 2
n= sample size of each group. σ = standard deviation 8.65 Z = reliability coefficient. 1.96 α
= significance level. 0.05 Zβ= at 20% power 0.84 μ1 = mean (Probiotic) 18.09 μ2 = mean
(Control) 23.21 d = mean difference 5.12
Randomization and allocation concealment:
A block randomization list will be generated with the block sizes 4, 6 and 8. Two parallel
groups (1:1 ratio) of patients following computerized randomization will be produced. Prior
to the enrollment of the patients a sequentially generated number with the treatment group
will be written in sealed envelope, which will be prepared by independent dermatologist.
Interventional and conventional groups:
Interventional group: Children with AD meeting eligibility criteria receiving probiotics and
conventional treatment (topical corticosteroid, topical tacrolimus, an oral antihistamine and
emollients) Conventional group: Children with AD meeting eligibility criteria, under
conventional treatment only.
Follow up:
Each patient will be asked for their follow up at 2, 4, 6, 8, 10 and 12 weeks of commencing
treatment. In each follow up, every patient will be evaluated for the side effects and
compliance to treatment. SCORAD index will be measured at baseline and at 4, 8, 10 and 12
weeks. FDLQI will be measured at baseline and at 8 weeks. Parents will be provided a card to
record for flare of symptoms; total days of steroid use for the same and total flare episode
will be recorded during 12 weeks follow up. Flare is defined as worsening of clinical
features leading to use of corticosteroids for at least 3 consecutive days.
Family dermatology life quality index:
Parents or guardian of each children will be asked to fill the questionnaire intended to
measure quality of life of family members whose relative have dermatological conditions. The
standardized nepali version of FDLQI (MKA Basra, AY Finlay. Cardiff University 2005) will be
used. Questions concern the influence of disease on parents QOL in the last month. Each
question can be answered by selecting 1 out of 4 answers scored 0-3. The maximum score is 30
points and minimum 0 point. The higher the score lower the parents QOL.
Severity Index (SCORAD) It uses the rule of nine to assess extent of disease and evaluates
five clinical characteristics to determine disease severity: i) erythema, ii) edema/
papulation, iii) oozing/crusts, iv) excoriation and v) lichenification. It also assesses
subjective symptoms of pruritus and sleep loss with Visual Analogue Scales (VAS).
Based on SCORAD score, AD is categorized as
- Mild AD (SCORAD <25)
- Moderate (SCORAD 25-50)
- Severe (SCORAD >50)
Statistical Analysis:
Statistical analysis will be conducted both per protocol and intention to treat population
(defined as all enrolled children to whom study drug will be given; with the last observation
carried forward) basis using two sided tests.
Statistical methods proposed:
1. Descriptive statistics will be summarized as mean, median, percentage, standard
deviation (SD) and interquartile range along with appropriate graphical and tabular
presentation.
2. Intragroup SCORAD index and FDLQI score will be compared by paired t-test and between
the groups by independent t- test.
3. In case of nonparametric data Mann- Whitney U test for independent groups and Wilcoxon
signed- rank test for paired group will be used.
4. Chi-square test will be used to compare the categorical data. All statistical tests will
be carried out at a significance level P<0.05.
