Controlled Trial of Chinese Herbal Medicine to Treat Allergic Rhinitis
Condition: Allergic Rhinitis
MeSH terms: Rhinitis; Rhinitis, Allergic
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The aim of this study is to test and compare the effectiveness between three groups -
      Cure-Allergic Rhinitis Syrup (CS), Yuk ping fung San (YS) and placebo groups - of adolescents
      (nursing students) with Allergic Rhinitis (AR) in improving their symptoms of AR, body
      constitution pattern and health-related quality of life.

      • The hypothesis are to test the effectiveness of the CS treatment on these students' AR
      symptoms and quality of life at immediately, one month and two months after completion of the
      4-week intervention, when compared with the YS treatment and placebo group.

        1. Cure-Allergic Rhinitis Syrup (CS) group will show significantly reduction of AR symptoms
           over the 2-month follow-up, when compared to those in YS and placebo groups.

        2. CS group will indicate a healthier body constitution pattern over the follow-up, when
           compared to those with YS and placebo group.

        3. CS group will indicate significantly greater improvement of their quality of life over
           2-month follow-up, when compared to those with YS and placebo group.
    

Detailed description: 
      Background

        -  Rhinitis (AR) is one of the most concerned public health problems worldwide, resulting
           from an inflammation of nasal membranes.

        -  Nursing students is one of the high risk groups, particularly when performing clinical
           practicum in hospitals in which they would contact with multiple allergens such as
           micro-organisms, detergents, chemical agents, and frequently used powdered latex gloves.
           More than 10% of these adolescents would present consistent AR symptoms such as nasal
           congestion, sneezing and sleep problems and In turn, these symptoms could affect their
           quality of life and academic performance.

        -  Non-compliance to medication or refusals to medical advice was common due to lack of
           efficacy, side effects, fear of being habit-forming, and/or expensive medical costs; and
           thus many preferred an alternative therapy for improved symptoms and bodily condition,
           and even full recovery.

        -  Chinese medicine treats the disease from the root, which is a complementary and
           alternative approach for holistic convalescence by changing unhealthy body constitution
           (health status) to healthy. However, little scientific evidence has been established for
           the treatment of AR with Chinese herbal medicine.

        -  This study aims to test the effects of two alternative treatments of Chinese herbal
           medicine, including Cure-Allergic Rhinitis Syrup (CS) and Yuk ping fung San, when
           compared with a placebo (i.e., wheat syrup with similar taste and smell) group, in
           reducing university nursing students' AR symptom severity and improving their quality of
           life and body constitution.

      Methodology

        -  A double-blind randomized controlled trial with repeated-measures, three parallel groups
           design is adopted.

        -  Assessment and follow-ups would be taken place in an Integrative Health Clinic of The
           University under study.

        -  Stratified random sampling method in terms of the students' years of illness onset and
           gender has been used to allocate the subjects into one of the three study groups.

        -  Participants, assessor and researcher are concealed and blinded to the random group
           allocation, which would be performed by an independent clinic nurse.

        -  In order to maintain complete blinding, a clinic nurse will also administer the herbal
           medicine and keep the name list locked, and thus being confidential.

        -  Participants would be recruited from all of five full-time undergraduate nursing
           programs in School of Nursing of The University. After their eligibility for inclusion
           checked and baseline measurement performed with informed consent obtained, the
           participants would be grouped in terms of duration of the illness (0-2 years, 2-5 years
           and 5 or above years) and gender and then each would draw one labeled card from an
           opaque envelope (1=CS, 2=YS and 3=Placebo) from the clinic nurse to allocate them into
           one of the three groups.

        -  Quality of life and symptom severity would be measured with self-administered
           questionnaires, and body constitution assessment would be performed by an Traditional
           Chinese medicine (TCM) practitioner, at baseline and immediately, one-month and
           three-month after the 4-week intervention.

      Sampling

        -  All full-time nursing students in The University under study who met the inclusion
           criteria and voluntary to participate in this study are the potential subjects.

        -  Sample size calculation has been calculated in the basis of similar Chinese herbal
           medicine effects in improving AR symptoms (primary outcome) in previous studies. Total
           sample size is 195 (n=65 per group) using G-Power based on the effect sizes (0.45) of
           two similar recent studies (Jung, 2011; Yang, 2010). Taking account of about 20%
           drop-outs, the estimated sample size becomes 234, thus 78 participants in each group.

      Intervention

        -  Cure-Allergic Rhinitis Syrup (CS) and Yuk ping fung San (YS) are adopted as the two
           alternative treatments to be tested in this study, while the placebo group will be the
           controls in this study.

        -  Medication will be produced and provided by the researcher. CS contains 12 Chinese
           herbal medicines in one formula, combining 3 classical ancient formula of herbal
           medicine that are commonly used to enhance healthy body constitution. YS contains 6
           herbal medicines, which are commonly used for AR treatment, while the placebo contains
           wheat powder, sugar and spicy taste of food (ginger).

        -  Boiling methods for CS and YS are the same, in which the herbal medicines will be boiled
           with 2000 ml of water for two hours after cleansing to about 500 ml herbal concoction.

        -  Participants would be asked to take 20 ml per dosage on each day, by diluting two spoons
           with a half cup of water either in the morning or at night, at their convenience.

        -  One bottle for two-week dosage would be offered after the first assessment at
           recruitment; and another bottle for the remaining 2-week dosage would be given during
           the first follow-up by the end of 2nd week (Interim assessment). Each participant would
           have to take in total of four weeks herbal medicine.

      Ethical issues

        -  Ethical approval of this study will be obtained from the Human Subjects Research Ethics
           Sub-committee of The Hong Kong Polytechnic University.

        -  Written informed consent will be obtained from the respondents to show their willingness
           of participation. In order to enhance full understanding of the study before
           participation, an information sheet to describe in more details about the aim and
           procedure of the study will be given with explanations before signing the written
           consent.

        -  Study data and participant identity are kept anonymous and confidential. Data collected
           are limited in access by the researcher and clinic nurse for study purpose only. The
           data will be destroyed after completion of the study and thesis writing.

        -  Precaution of adverse effects would be taken on the herbal medicine selection
           (double-checked by an independent TCM practitioner), medicine formation (agreed by at
           least two TCM practitioners), time of boiling, and interim assessment (by one TCM
           practitioner) and weekly or bi-weekly face-to-face or telephone follow-ups (by the
           researcher). Students are reminded of reporting any discomfort and asking questions
           about the illness and the study. They are given the contact telephone of the researcher
           and would be referred to Western medicine or TCM practitioner for follow-up, as needed.

        -  All herbal medicine items should be within normal and recommended dosage. Any toxic
           effect of the herbal medicines used is reduced by long boiling and minimal dosage.

        -  Before random group allocation, all participants are assessed and confirmed with the
           body constitution pattern(s) by one TCM practitioner and history of allergy to herbal
           medicines, particularly those items adopted in the study, will be checked. Those with
           such allergies, inappropriate body constitution for the herbal medicines used, or very
           poor body condition, would be excluded.

        -  Monitoring of exceptional allergy such as skin rash and related discomforts would be
           performed over the first 2 weeks of syrup intake. At the end of the 1st and 3rd week of
           intervention, the researcher would phone up each participant to ask about any concern or
           discomfort experienced.

        -  Monitoring the health parameters such as body temperature, blood pressure, pulse rate,
           respiratory rate, and urine for routine testing to assess and understand the
           participants' health condition and detect possible adverse effect of herbal medicines
           during interim assessment (2nd week of intervention).

        -  Although very low risk for adverse events (<0.1%), the researcher would terminate the
           herbal medicine used and ask the participant to attend Accident and Emergency Department
           immediately if any found such as serious allergy, skin rash or any illness such as fever
           or systemic infection, which might be related to signs of over reinforcement of Yang
           inside the body.

        -  The TCM practitioner will also monitor any uncommon effects on renal and liver functions
           such as diarrhea, urinary tract infection, pain, and skin rash in the 2nd and 4th week
           assessments.

      Instruments

        -  Constitution in Chinese Medicine Questionnaire

           o 60 items of Constitution in Chinese Medicine Questionnaire can assess the
           participants' body constitution.

        -  Quality of life and symptom severity

             -  The 28-item Rhino-conjunctivitis Quality of Life Questionnaire is adopted to
                evaluate the participants' level of quality of life; and

             -  The same questionnaire is also used for assessing their symptoms severity.

        -  Objective assessment of nasal symptoms

        -  Peak Nasal Inspiration Flow Meter will be adopted to monitor the nasal symptom
           (blockage)

        -  Demographic and other clinical information Pilot Study

        -  Fifteen participants (i.e. five nursing students in each of three study groups) would be
           recruited for a pilot study. The pilot study is conducted with the same procedure of TCM
           assessment, and herbal medicines used.

        -  Data collection with all the questionnaires, health assessment, follow-ups and data
           analysis will be performed similar to the main study.

        -  Purposes of the pilot study are to test the feasibility and procedure of the study,
           evaluate the validity and reliability of the questionnaires, examine any possible
           difficulty in sample recruitment and data collection, as well as check the estimated
           sample size used in the main study. Very minor amendments or modifications have been
           made on the procedure of the main study according to its results.

      Data Collection

        -  Data collection would be performed at four time points: baseline measurement (Time 1) at
           recruitment and three post-tests (Times 2-4) (immediately, and 1-month and 3-month
           following the interventions).

        -  Baseline assessment would be done to determine the eligibility for participant enrolment
           (making diagnosis of AR and differentiating their body constitution) and performing
           baseline measurements (mainly symptom severity, quality of life and body constitution)
           for the study. After 2-week interim assessment and 4-week intervention, subsequent three
           post-tests would be performed using the same sets of questionnaires for evaluation of
           treatment effect and comparison between and within groups.

        -  All assessments and data collection procedures would be performed in the Integrated
           Health Clinic, the participants will self-administer the study questionnaires, be
           assessed by the same TCM practitioner on body constitution and perform other health
           assessments such as vital signs and urine testing.
    

Intervention name(s): Cure-Allergic Rhinitis Syrup; Yu-ping-fung San; Placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Delivered one bottle for two weeks to the participants twice; Delivered one bottle for 2-week usage to the participants twice; Delivered one bottle (wheat power with favors) for 2-week usage to the participants twice
Other intervention name(s): CS group; YS group; Placebo/Control
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Allergic Rhinitis; Chinese herbal medicine; Adolescents; Double-blinded; Randomized controlled trial