Efficacy and safety of sterols/sterolins in allergic rhinitis: a

Formosan Journal of Rheumatology 2009;23:72-82
Original Article
Efficacy and safety of sterols/sterolins in allergic rhinitis:
a randomised double blind placebo-controlled clinical trial
Yi-Ling Chen1, Ming-Shiou Jan2, Ming-Yung Lee3, Li-Jie Shiu4, Bor-Luen Chiang5,
James Cheng-Chung Wei1,6
1
Department of Internal Medicine, Division of Allergy, Immunology and Rheumatology, Chung Shan Medical
University Hospital, Taichung, Taiwan
2
Department of Medicine, Chung Shan Medical University, Taichung, Taiwan
3
Clinical Trial Center, Chung Shan Medical University Hospital, Taichung, Taiwan
4
Chinese Medicine Clinical Trial Center; Institute of Public Health, Chung Shan Medical University,
Taichung, Taiwan
5
Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
6
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
Objective: Sterols/sterolins (Moducare®) have demonstrated immunomodulation and anti-inflammatory
effects in preclinical studies, but no clinical trial of patients with allergic rhinitis has yet been published.
Thus, our aim was to investigate the safety and efficacy of sterols/sterolins in patients with allergic rhinitis.
Methods: The framework was a pilot double-blind randomized controlled clinical trial. Forty patients
were randomized to receive Moducare® capsules or placebos for 12 weeks. Patients were evaluated at
weeks 4, 8 and 12 with symptom severity questionnaires and immunological assays, including: serum total
immunoglobulin E (IgE), eosinophil, and eosinophil cationic protein (ECP). The primary efficacy endpoint
indicated the mean change of the allergic rhinitis symptoms score in the therapeutic period at week 12;
the secondary efficacy endpoints represented the changes of the Mini-Rhinoconjunctivitis Quality of Life
Questionnaire (Mini-RQLQ) monthly score and the immunological assays of IgE, eosinophil and ECP at
week 12.
Results: A total of 28 patients (70%) completed the 12-week study, with eight patients dropping out of the
Moducare® group and four patients dropping out of the placebo group. The results showed no significant
adverse events of sterols/sterolins in this 12-week study. The results of the allergic rhinitis symptoms score,
Mini-RQLQ, total IgE, eosinophil count and ECP value had no statistically significant changes in either
group.
Conclusions: While sterols/sterolins were well tolerated and safe in patients with allergic rhinitis, no
significant clinical and immunological benefits were demonstrated in this 12-week pilot study.
Key words: Pilot study, allergic rhinitis, immunomodulation, Moducare, sterols/sterolins
Corresponding author: James Cheng-Chung Wei M.D., Ph.D.
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Division of Allergy, Immunology and Rheumatology, Chung Shan
Medical University Hospital, Taichung, Taiwan.
No. 110, Sec. 1, Jianguo N. Rd., South District, Taichung City 40201, Taiwan
Tel: +886-4-24739595 ext 34310, Fax: +886-4-24739220
E-mail: [email protected]
Received: August 24, 2009
Revised: September 21, 2009
Accepted: October 8, 2009
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Chen et al
Introduction
Allergic rhinitis is a global health problem, especially
in children and teenagers, because of its high prevalence
and under-diagnosis [1,2]. From 1998 to 2001, patients
in the United States with allergic rhinitis were numbering
40 million annually, about 20% of the population [3,4].
The global prevalence of allergic rhinitis was 25%-35%
[5,6], numbering about 600 million people worldwide
[7]. In Taiwan, children aged 6-8 had significantly
high prevalence rates of rhinitis at 29.8% [8], and
adults had prevalence rates from 13% to 15% [9]. As
such, allergic rhinitis is currently a major source of
concern to many Taiwanese out-patient departments
[10]. Patients with allergic rhinitis reported not only
symptoms of rhinorrhea, nasal congestion, sneezing,
itching, and associated eye problems, but also that their
emotional well-being, social functioning, and quality of
life were affected [3]. There is accumulating evidence
that both genetic [11] and environmental factors [12]
play important roles in the etiology of allergic rhinitis.
Along with other known risk factors, allergic rhinitis is
considered a risk factor for asthma [2].
Allergic rhinitis results from an IgE mediated
response associated with an activation and differentiation
of different inflammatory cells [13] stimulated by
antigen-presenting cells (APC), including eosinophils,
T cells, mast cells, and basophils [14]. Helper T cells
(TH cell) also play a key role in humeral and cellular
immunity reaction regulation. The helper T cell can
be sub-classified as both TH1 and TH2 cells, which
produce different cytokines and perform different
functions [15]. TH1 secretes interleukin-12 and
produces TH1 cytokine such as interleukin-2 (IL-2) and
interferon-γ (IFN-γ) while TH2 predominates under
IL-4 stimulation with TH2 cytokine production such as
IL-4, IL-5, IL-6, IL-10, IL-13. Allergic inflammation
is associated with a shift in the balance between
cytokines produced by TH1 and TH2 cells toward
TH2 predominance. TH2 cytokines, such as IL-4,
IL-5, and IL-6, induce production of IgE, eosinophilia,
and the release of eosinophil cationic protein (ECP)
[16]. Treatment of allergic rhinitis is challenging and
expensive, often requiring environmental control,
pharmacotherapy, immunotherapy, and even surgical
intervention. Additionally, many drugs, such as
glucocorticoids, have significant side effects and
irreversible effects when used long term, most notably in
children.
Sitosterol (sterols) (BSS) is the major phytosterol in
plants, and is found in the serum and tissues of healthy
individuals at concentrations 800-1000 times lower
than that of endogenous cholesterol [17]. Its glycoside,
β-sitosterol glycoside (sterolins) (BSSG), is also present
in serum in even lower concentrations [18]. Moducare
is a mixture of sitosterol (BSS) and its glucoside,
β-sitosterolin (BSSG), in a 100:1 ratio (sterols 20 mg and
sterolins 0.2 mg). Previous in vitro studies revealed that
the BSS:BSSG mixture has immunomodulatory effects
and can restore TH1 and TH2 balance. It enhanced the
secretion of IL-2 and IFN-γ, but inhibited the secretion
of IL-4 [19] and was able to significantly enhance the
expression of CD25 and HLA-DR activation antigens
on T-cells and increased the secretion of IL-2 and
gamma interferon [20] into the medium. NK-cell
activity was also increased in the in vitro study [20].
There are also researches pertaining to the inhibition
of pro-inflammatory cytokine such as IL-6 and TNF-α
produced by monocyte and enhancing APC to produce
IL-12, helping helper T cells toward TH1[21-23]. The
mixture also has adreno-cortical effects by decreasing
the cortisol: the DHEA ratio suggesting that it can reduce
an inflammatory response [24]. Researches showing the
clinical efficacy of β-sitosterol and its glucoside in the
treatment of HIV-infected patients [21,25], rheumatoid
arthritis [26], and pulmonary tuberculosis [27] have
been published. However, no clinical trial data regarding
allergic patients have yet been published. Thus, we
performed this randomized, double-blind, placebo
controlled trial to evaluate the safety and efficacy of
Moducare® in patients with allergic rhinitis.
Materials and Methods
This study was approved by the Institutional Review
Board (IRB number CS05035) to perform the study
at the Clinical Trial Center of Chung Shan Medical
University Hospital, Taichung, Taiwan.
Patients
This randomized, double-blind, placebo-controlled
trial used a total of 40 patients who were diagnosed with
allergic rhinitis by a physician according to the clinical
symptoms and a positive in vitro specific serum IgE test
of mite (D. pteronyssinus). The clinical symptoms were
measured on the Score For Allergic Rhinitis (SFAR)
and those patients who scored with a value greater than
eight were enrolled from an out-patient department.
The assessment score contained 8 items, 15 questions
and 16 total points, including nasal symptoms in the
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STEROLS/STEROLINS in allergic rhinitis
past year, rhinoconjunctivitis symptoms, months of the
year in which nasal symptoms occur, triggers of nasal
symptoms, perceived allergic status, previous medical
diagnosis of allergy, previous positive tests of allergy
and familial history of allergy [28]. Patients were
eligible for inclusion if they had been receiving stable
allergen-specific subcutaneous immunotherapy for at
least 6 months or stable oral anti-histamine therapy for
one month. Exclusion criteria were as follows: those
with leukemia, lymphoma, diabetes mellitus, as well
as breast-feeding women and organ transplant patients.
All patients were randomly assigned to receive either
Moducare® or placebo therapy, which consisted of one
capsule, three times a day, and one hour prior to meals
for 12 weeks. The capsule could not be ingested with
steroids, eggs, milk, or meat.
headache. The answers were graded on a scale from
0 to 5: 0 = no symptoms, 1 = slight, 2 = mild, 3 =
moderate, 4 = severe, 5 = very severe. We also assessed
the patients’ quality of life through a self-administered
Chinese version Mini-RQLQ score (Table 1). We asked
whether patients were troubled by nasal symptoms,
eye symptoms, activity, practice problems and other
symptoms with 14 questions on a scale from 0 to 6: 0 =
not troubled, 1 = hardly troubled, 2 = somewhat troubled,
3 = moderately troubled, 4 = quite a bit troubled, 5 =
very troubled, 6 = extremely troubled. In addition, there
was a questionnaire to determine the frequency and
severity of symptoms with seven questions on a scale
from 0 to 6: 0 = not at all, 1 =rarely, 2 = sometimes, 3 =
occasionally, 4 = often, 5 = most of the time, 6 = all of
the time.
Clinical outcome assessment
Assessment of adverse reactions
All patients were assessed at weeks 0, 4, 8, and 12
at an out-patient department and discontinued antiallergic therapy 24 h before every assessment. The
clinical efficacy assessment included general physical
examinations, self-administered allergic rhinitis
symptoms scores, and the Mini-RQLQ scores. The
primary efficacy endpoint was the mean change from
the baseline over the entire treatment period of allergic
rhinitis symptoms scores at week 12. The secondary
endpoint was the mean change from the baseline over
the treatment period in the Mini-RQLQ scores monthly
and serum levels of IgE, eosinophil, and ECP at week
12.
The allergic rhinitis symptoms score and
the Mini-Rhinoconjunctivitis Quality of Life
Questionnaire (Mini-RQLQ) score
The allergic rhinitis symptoms score and the MiniRQLQ score were used to assess the severity of patients
with allergic rhinitis during the treatment period. The
allergic rhinitis symptoms score was attained through
a self-administered Chinese version questionnaire
consisting of 23 questions where responses included: (a)
rhinitis symptoms: total nasal symptoms score (TNSS,
including nasal congestion, rhinorrhea, nasal itching, and
sneezing) plus post nasal drip, olfactory dysfunction,
and snoring; (b) eye symptoms ( total ocular symptoms
score, TOSS): itching eyes, burning eyes, tearing/
watering eyes, and eye redness; (c) chest symptoms:
cough, wheezing, chest tightness, dyspnea, and chest
pain; and (d) general symptoms: fatigue, sleeping
disturbance, weakness, anxiety, inertia, dizziness, and
74
Any adverse events were reported and recorded
during each visit. Serum creatinine, lactate dehydrogenase
(LDH), Aspartate aminotransferase (AST), and Alanine
transaminase (ALT) were checked at week 0 and week
12 for renal and hepatic function assessment.
Statistical analysis
The study was based on an intent-to-treat analysis,
and missing values were managed using the LVCF
method (Last Value Carried Forward). Comparisons
between the therapeutic group and the placebo group
for baseline characteristics were performed using the
Wilcoxon rank-sum test in continuous data or Chisquare tests in categories at week 0. Comparisons during
each visit (at weeks 0, 4, 8, 12) between each group were
assessed using the Wilcoxon rank-sum test. Comparisons
before and after treatment in each group were assessed
using the Wilcoxon signed-rank test. Analyses were
performed using software SAS, vision 9.1; p values less
than 0.05 were considered significant.
Results
Forty patients were enrolled in this study. A total of
28 patients (70%) completed the 12-week study, with
eight patients dropping out of the Moducare® group (two
due to inefficacy, one due to the development of pelvic
inflammation, and five due to a failure to return) and four
patients in the placebo group (one due to insufficient
therapeutic response, one due to the development of a
rash, and two due to failure to return) (Fig. 1).
The demographic features of the 40 patients on the
Chen et al
Figure 1. Patient disposition.
baseline are shown in Table 1. There were no significant
statistical differences between the two groups in age
(32.5 in the Moducare® therapy group and 35.7 in the
placebo group, p=0.453), and gender (male percentage
65.0% in the Moducare® group and 45.0% in the
placebo group, p=0.204). There were no significant
statistical differences in the rhinitis symptoms score (9.6
in the Moducare® group and 12.4 in the placebo group,
p=0.192), eye symptoms score (3.7 in the Moducare
® group and 3.8 in the placebo group, p=0.538), chest
symptoms score (4.4 in the Moducare® group and 4.9 in
the placebo group, p=0.375) and general symptoms (3.7
in the Moducare® group and 3.8 in the placebo group,
p=0.127) assessed through a self-administered allergic
rhinitis symptoms score in the initial stage of the study
between the two groups. The self-administered MiniRQLQ score at the baseline showed lower symptom
scores in the Moducare® group than the placebo group (
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STEROLS/STEROLINS in allergic rhinitis
Table 1. Mini Rhinoconjunctivitis Quality of Life Questionnaire
Not troubled
Activity
Regular activities at home and
at work
Recreational activities
Sleep
Practical problems
Need to rub nose/eyes
Need to blow nose repeatedly
Nose symptoms
Sneezing
Stuffy blocked nose
Runny nose
Eye symptoms
Itchy eyes
Sore eyes
Watery eyes
Other symptoms
Tiredness and/or fatigue
Thirst
Feeling irritable
0
Hardly troubled Somewhat Moderately
Quite
Extremely
Very troubled
at all
troubled
troubled a bit troubled
troubled
1
2
3
4
5
6
0
1
2
3
4
5
6
0
1
2
3
4
5
6
0
1
2
3
4
5
6
0
1
2
3
4
5
6
total points 26.0 ± 16.8 vs. 36.2 ± 14.7, p=0.095), but the
scores disclosed no significant statistical differences. In a
biochemical study, higher values of IgE (686.6 vs. 358.3,
p=0.356), lower ECP (22.8 vs. 36.0, p=0.234), and lower
eosinophil (250.0 vs. 340.5, p=0.134) were noted in the
Moducare® group than in the placebo group with no
significant statistical differences. Patient demographics
and baseline characteristics were similar between the
two groups (Table 2).
During the safety assessment, two episodes of
adverse events were reported. One was an allergic rash
over the arm and thigh in the placebo group, which
Table 2. Clinical and demographic data at baseline
Demographics
Age, years (mean ± SD)
Gender n, male (%)
Symptoms score (mean ± SD)
Rhinitis symptoms [range: 0-35]
Eye symptoms [range: 0-20]
Chest symptoms [range: 0-25]
General symptoms [range: 0-35]
Mini-RQLQ (mean ± SD)
Activity [range: 0-18]
practice problems [range: 0-12]
nose symptoms [range: 0-18]
eye symptoms [range: 0-18]
other symptoms [range: 0-18]
Total points [range: 0-84]
Laboratory values (mean ± SD)
Immunoglobulin E (IgE) IU/mL
ECP μg/L
Eosinophil/mm+
Abbreviation: ECP = eosinophil cationic protein
a
p<0.05
76
Moducare® (n = 20)
Placebo (n = 20)
p
32.5 ± 14.4
13(65%)
35.7 ± 12.1
9(45%)
0.453
0.204
9.6 ± 6.9
3.7 ± 4.7
4.4 ± 4.9
6.7 ± 7.1
12.4 ± 6.1
3.8 ± 4.2
4.9 ± 7.2
8.9 ± 6.8
0.192
0.538
0.375
0.127
4.4 ± 4.1
4.6 ± 3.1
7.0 ± 3.7
5.1 ± 4.1
4.9 ± 3.7
26 ± 16.8
7.8 ± 3.9
5.6 ± 3.5
9.6 ± 4.2
6.5 ± 3.9
6.6 ± 3.5
36.2 ± 14.7
0.034a
0.407
0.098
0.347
0.213
0.095
686.6 ± 771.3
22.8 ± 28.7
250.0 ± 230.3
358.3 ± 441.1
36.0 ± 34.2
340.5 ± 235.7
0.356
0.234
0.134
Chen et al
Figure 2. The Mini-RQLQ score: activity (A), practice problems (B), nose symptoms(C), eye symptoms (D), other
symptoms (E) and total points (F) of the patient treated with Moducare® or placebo over the 12-week treatment period.
improved after discontinuing the therapy and was treated
with topical steroid ointment and oral antihistamine. The
other was acute pelvic inflammation in the Moducare
® group, which was cured after antibiotic therapy. The
toxicity to liver and kidney was monitored at week 0 and
week 12. The week 0 baseline Moducare® group had
a higher creatinine value (1.0 vs. 0.9 mg/dL, p=0.248),
AST value (20.4 vs. 19.2 IU/L, p=0.706), ALT (21.2 vs.
17.8 IU/L, p=0.222), and LDH value (493.1 vs. 476.7
IU/L, p=0.697) which showed no statistical difference
and was within normal range. At the end of the treatment
period, the Moducare® group had lower creatinine
(1.0 vs. 1.0 mg/dL, p=0.592), AST (19.0 vs. 21.2 IU/L,
p=0.893), ALT (18.7 vs. 22.7 IU/L, p=0.273) and LDH
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STEROLS/STEROLINS in allergic rhinitis
Table 3. Adverse events and safety in patients treated
with either Moducare® or placebo
Moducare®
(n = 20)
Table 4. Mean change in the symptoms score after
treatment with either Moducare® or placebo
Placebo
(n = 20)
Adverse events, n (%)
Exanthema
1 (5.0%)
0 (0.0%)
Pelvic inflammation
0 (0.0%)
1 (5.0%)
Biochemistry value at week 0 (mean ± SD)
Creatinine
1.0 ± 0.2
0.9 ± 0.2
AST
20.4 ± 7.7
19.2 ± 8.1
ALT
21.2 ± 13.5
17.8 ± 19.2
LDH
493.1 ± 132.0 476.7 ± 144.8
Biochemistry value at week 12 (mean ± SD)
Creatinine
1.0 ± 0.2
1.0 ± 0.2
AST
19.0 ± 5.0
21.2 ± 15.5
ALT
18.7 ± 9.8
22.7 ± 39.3
LDH
474.1 ± 102.1 484.9 ± 152.2
Abbreviations: AST = aspartate aminotransferase; ALT = alanine
transaminase; LDH = lactic dehydrogenase
(474.1 vs. 484.9 IU/L, p=0.803) which showed no
statistical difference (Table 3).
The primary efficacy endpoint revealed a declining
trend in rhinitis symptoms, eye symptoms, chest
symptoms, and general symptoms at week 12 in the
Moducare® group, but the mean change showed no
significant statistical difference from the baseline. In the
placebo group, a more significant declining trend was
noted in all types of symptoms and the mean change had
a statistical difference from the baseline in the rhinitis
symptoms score (–4.9 ± 4.2, p=0.002); chest symptoms
score (–1.6 ± 3.1, p=0.035), and general symptoms score
(–3.0 ± 4.4, p=0.002) (Table 4).
The Mini-RQLQ score also showed a declining
trend but without significant statistical difference in both
groups at weeks 4, 8, and 12 from the baseline (Fig. 2).
Compared with the placebo group, the Moducare®
therapy group has a higher IgE level (664.3 vs. 408.4 IU/
mL, p=0.830), lower ECP concentration (24.1 vs. 31.2
μg/L, p=0.845), and lower eosinophil count (248.0 vs.
289.6/mm3, p=0.638) at the end of the study. This data
showed no significant statistical differences (Table 5).
mean change ± SD
Rhinitis symptoms
Eye symptoms
Chest symptoms
General symptoms
a
Moducare®
(n = 20)
Placebo
(n = 20)
–0.9 ± 6.1
–0.5 ± 3.3
–0.2 ± 3.2
–0.2 ± 4.8
–4.9 ± 4.2a
–0.8 ± 3.1
–1.6 ± 3.1a
–3.0 ± 4.4a
p<0.05
Discussion
Allergic rhinitis patients generally suffer from a
serious life quality impairment [29,30] The total burden
of allergic disease lies in not only impaired physical and
social functioning but also financial burden, which even
greater if co-morbidities with asthma or sinusitis [31].
If there are promising agents with fewer side effects in
the current treatment of allergic rhinitis, the impact of
allergic rhinitis might decline. In our study, the mean
change of allergic rhinitis symptom scores and the MiniRQLQ scores between the therapeutic group and the
placebo group revealed a declining trend during the
study period but without significant statistical differences
at weeks 4, 8, and 12 respectively. This outcome might
be linked to season and climate change related to allergic
rhinitis, as our study took place starting at the end of
spring and ending at the beginning of autumn. Another
reason could be that the higher allergic symptoms and
the Mini-RQLQ scores in the placebo group at week 0
caused a regression toward the mean effect, creating a
significant trend of decline. A longer period and a greater
number of study samples may be required to reduce the
inaccuracy. The complete rate (60% in the Moducare
® group vs. 80% in the placebo group) was higher in
the placebo group possibly because of the correlation
between more serious symptoms and better compliance. We chose not only the Score For Allergic Rhinitis
(SFAR), which has the sensitivity of 74%, specificity
of 83%, positive predictive value of 84% and negative
predictive value of 74%, but also the in vitro serum
specific allergen IgE test, which has no anaphylactic
Table 5. Value of immunological assays after 12 weeks of either Moducare® or placebo
Parameters
IgE IU/mL
ECP μg/L
Eosinophil /mm3
Moducare® (n = 20)
Baseline
12 weeks
686.6 ± 771.3
664.3 ± 736.9
22.8 ± 28.7
24.1 ± 26.1
250.0 ± 230.3
248.0 ± 175.0
Abbreviation: ECP = eosinophil cationic protein
78
Placebo (n = 20)
Baseline
12 weeks
358.3 ± 441
408.4 ± 484.4
36.0 ± 34.2
31.2 ± 32.4
340.5 ± 235
289.6 ± 203.5
Chen et al
reaction risk for disease diagnosis. There were several
objective measures of the severity of allergy rhinitis,
including symptoms scores, visual analogous scales
(VAS), peak inspiratory flow measurements, acoustic
rhinometry and rhinomanometry for nasal obstruction
measurement, cells and mediators in nasal lavages,
nasal biopsy for inflammation measurement, reactivity
measurement by provocation test and sense of smell
test. In our study, self-administered questionnaires were
used to assess the severity of allergic rhinitis. This is a
satisfactory methodology for investigating the severity
of allergic rhinitis due to the notion that few biochemical
values corresponding to the real clinical symptoms
as well as the fact that immunological assays were
restrictively time-consuming. The literature supports
our decision as questionnaires have shown acceptable
reliability and responsiveness [32-34]. However,
although the questionnaires were fast and corresponded
to clinical symptoms, there was no perfect standard
for score grading. Allergic rhinitis presents not only
nasal symptoms but also eye, upper airways, lower
airways, and systemic symptoms. Using the Total Nasal
Symptoms score for disease assessment is insufficient.
The allergic rhinitis symptoms score contains the TNSS,
TOSS, chest symptoms, and general symptoms; it
provide generalized quantitative assessment of allergic
rhinitis. The Mini-RQLQ was the abbreviated version
of 28-item RQLQ for large clinical trials, surveys, and
practice monitoring use. The highest scoring items of
RQLQ were selected for the 15 questions Mini-RQLQ.
Responsiveness to change in clinical status was better
with the Mini-RQLQ than with the RQLQ [32].
Immunological assays of IgE [35,36], eosinophil
[13,29,36-38] and ECP [30,35,36,39,40] were correlated
to allergic rhinitis. Higher IgE concentrations and lower
ECP and lower eosinophil counts in the therapeutic
group were found in our study but had no statistical
differences. Elevated IgE shows that the patient came
into contact with an allergen but no temporal certainty is
guaranteed. Serum IgE could exist stably for weeks if it
combined with basophil or mast cells. ECP is granular
protein in eosinophil and is elevated with inflammation,
allergy, and parasitic invasion. Notably, some studies
indicated that ECP had no correlation to the severity
of asthma and allergic rhinitis. Allergen avoidance
and environment control were the important factors of
allergic disease control. In our study, poor therapeutic
response of clinical symptoms may be secondary to
persistent environment allergen stimulation proven by
the ECP value in both groups.
Conclusion
This is the first randomized double blind placebocontrolled clinical study to evaluate the efficacy of
Moducare® on allergic rhinitis. This natural product
was found to be safe without liver and renal toxicity
and was well tolerated in patients with allergic rhinitis.
The results of the 12-week trial period did not show
significant improvement of clinical symptoms and
immunological assays in the Moducare® group.
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STEROLS/STEROLINS in allergic rhinitis
Sterols/sterolins治療過敏性鼻炎之隨機雙盲安慰劑對照式臨
床試驗
1
陳依伶
2
詹明修
3
李名鏞
許立潔
4
5
江伯倫
6
魏正宗
1
中山醫學大學 附設醫院 內科部 風濕免疫過敏科
中山醫學大學 醫學系
3
中山醫學大學 附設醫院 臨床試驗中心
4
中山醫學大學 公共衛生研究所 中藥臨床試驗中心
5
台灣大學 附設醫院 小兒部
6
中山醫學大學 醫學研究所 中山醫學大學 附設醫院 風濕免疫過敏科
2
全世界過敏性鼻炎盛行率因空氣品質與環境生態的改變於不斷攀升，雖然它不會造成生命上的威
脅但對於生活品質、工作、學業、及生產力皆造成顯著影響，其免疫病理特徵已被證實與TH2細胞
所分泌的細胞激素相關。Sterols/sterolins（Moducare®）在許多臨床前的研究中證實具有免疫調節
及抗發炎的作用，使TH1/TH2趨向平衡，但並無針對過敏性鼻炎的臨床實驗曾發表過。本研究的
目的在探討過敏性鼻炎的病人使用sterols/sterolins（Moducare®）的臨床療效與其安全性。本先導
性隨機雙盲安慰劑對照組試驗共納入40位病人分別接受Moducare® 或安慰劑治療12週，並分別在
第4、8、12週接受過敏性鼻炎嚴重度與生活品質評估問卷之調查與治療前後血清免疫學分析（IgE,
eosinophil cationic protein, eosinophil）來評估其效果。Moducare®臨床治療效果採意圖治療分析法
（intend-to treat analysis）評估，遺漏值之插補採用LVCF法（Last Value Carried Forward）。結果顯
示Moducare®治療組中20位進入試驗，12位完成試驗，安慰劑組中20位進入試驗，16位完成試驗，
兩組病人在過敏性鼻炎症狀評估表與生活品質評估表分數治療前後雖然都呈現下降趨勢但並無統
計上意義，血清免疫學分析在兩組治療前後亦無統計上意義。安全性指標（creatinine, AST, ALT）
中兩組病人皆在正常值範圍內，所有病人並無嚴重副作用或不良反應產生。由本研究中可知，
Moducare®治療過敏性鼻炎的病人在12週的治療中雖然是安全的但並無顯著的臨床療效與血清免疫
分析變化。
關鍵詞：先導性試驗，過敏性鼻炎，免疫調節，Moducare®，固醇/固醇苷（sterols/sterolins）
82