Clinical Efficacy and Serum Proteomic Profiling of Suan-Zao-Ren Tang for Sleep Disturbance During Methadone Maintenance

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy of Suan-Zao-Ren Tang in improving sleep quality, anxiety, depression, and heroin craving among methadone-maintained persons with sleep complaints.

Detailed Description
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Background: Heroin dependence is one of the major health issues worldwide. Methadone Maintenance Therapy (MMT) is an effective treatment for opioid dependence, but more than three quarters of persons receiving MMT report sleep complaints. Traditional Chinese Medicine (TCM) is one of the most common complementary therapies offered to insomnia patients in Taiwan. Investigators designed a randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy of TCM in methadone-maintained persons with sleep disturbance. Methods/design: In this study, inclusion criteria are persons receiving MMT for at least one month, more than 20 years old, complain insomnia with a Pittsburgh Sleep Quality Index (PSQI) of six or higher. Exclusion criteria include being pregnancy, had serious physical or mental illness, current use (last 30 days) of TCM, had received any antidepressant or neuroleptic medication and inability to read and fill out the forms for the study. The patients were separated into an intervention group (Suan-Zao-Ren Tang, SZRT) and a placebo group for four weeks using a randomized, double-blind procedure. Outcome measures will be assessed at baseline, 4 weeks and 8 weeks after receiving medication. PSQI was used to assess sleep quality over the past 30 days, anxiety and depression levels measured by the Beck Anxiety Inventory (BAI) and Beck Depression Inventory II (BDI-II) were also conducted, heroin craving degree was evaluated by the change of the visual analog scale (VAS). Serum proteins will be detected using a proteomics method based on two-dimensional gel electrophoresis, and the specificity of proteins will confirmed by western blotting. T-test and chi-square tests are used for statistical analysis. Discussion: SZRT is a combination of Semen Zizyphi Spinosae (Suanzaoren), Sclerotium Poriae Cocos (Fuling), Radix Ligustici Chuanxiong (Chuanxiong), Rhizoma Anemarrhena (Zhimu), and Radix Glycyrrhizae (Gancao). It was the most commonly prescribed Chinese herbal formula used for the treatment of insomnia. In the classical literature and previous studies, SZRT was said to calm the nerves and nourish the blood to eventually bring on a tranquillizing sensation and improved the quality of sleep without generating significant side effects. In order to evaluate the efficacy of SZRT for sleep disturbance during methadone maintenance, investigators designed a randomized, double-blind, placebo-controlled trial and perform the proteomic-system biology analysis to find the biomarker associated with sleep condition.

Official Title
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Clinical Efficacy and Serum Proteomic Profiling of Traditional Chinese Medicine, Suan-Zao-Ren Tang, for Sleep Disturbance During Methadone Maintenance: Study Protocol for a Randomized, Double-blind, Placebo-controlled Trial

Conditions
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Opiate Dependence

Intervention / Treatment
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* Drug: Suan-Zao-Ren Tang
* Drug: Suan-Zao-Ren Tang placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: aged over 20 years patients fulfilled the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for opiate dependence patients had been receiving MMT for more than one month patients have sleep disturbance complains and with Pittsburgh sleep quality index (PSQI) of greater than six Must be able to signed informed consent Exclusion Criteria: had received any antidepressant or neuroleptic medication had received any TCM treatment during the previous 30 days had any serious physical or mental illness had a significant risk of suicide pregnancy inability to read and fill out the forms for the study

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Suan-Zao-Ren Tang<br>The SZRT formula used in this study is manufactured as a herbal extract powder from the good manufacturing procedures (GMP) of the certified company Kaiser Pharmaceutical Co., Ltd. (Taiwan). Granules were packed in aluminum foil packages and administered orally at a dose of 4 g, three times per day for four weeks. | Drug: Suan-Zao-Ren Tang<br>* SZRT is composed of five herb ingredients as follows: Semen Zizyphi Spinosae (Suanzaoren), Sclerotium Poriae Cocos (Fuling), Radix Ligustici Chuanxiong (Chuanxiong), Rhizoma Anemarrhena (Zhimu), and Radix Glycyrrhizae (Gancao).The SZRT granules were packed in aluminum foil packages and administered orally at a dose of 4 g, three times per day for four weeks.<br>|
| Placebo Comparator: Suan-Zao-Ren Tang placebo<br>The Suan-Zao-Ren Tang placebo granules are prepared with 4 g starch inside the same colored and sized foil packages. | Drug: Suan-Zao-Ren Tang placebo<br>* The Suan-Zao-Ren Tang placebo granules are prepared with 4 g starch inside the same colored and sized foil packages.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| sleep quality | The primary outcome measure under study is the sleep quality. Sleep quality will be assessed using the Taiwanese version of the PSQI, which has demonstrated reliability and validity. It evaluates sleep disturbances in 7subscales: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication and daytime dysfunction. Each subscale is rated on a 4-point scale (0 to 3, with 3 indicating a more profound effect), which is summed together to yield a global score (0to21). | The patients will complete the questionnaire at baseline (first visit), four weeks later (second visit), and eight weeks later (third visit). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| severity of heroin craving | The severity of heroin craving was assessed using a 100 millimeters visual analog scale (VAS). | The patients will complete the questionnaire at baseline (first visit), four weeks later (second visit), and eight weeks later (third visit). | 
| Beck Anxiety inventory (BAI) | This measure lists 21 symptoms of anxiety such as feeling hot, scared or nervous. Participants will be instructed to rate how much each of these symptoms bothered them in the past week. Each item can be rated on a 4 point Likert scale, ranging from 0 (Not at all) to 3 (Severely) yielding a maximum total score of 63 points. | The patients will complete the questionnaire at baseline (first visit), four weeks later (second visit), and eight weeks later (third visit). | 
| Beck Depression Inventory (BDI-II, second edition) | Depression symptoms will be measured with the BDI-II. This measure consists of 13 items to evaluate depression, and each item is rated from 0 to 3 according to the degree by which it reflects a patient's state during the previous week. The BDI has a high reliability, and concurrent validity. | The patients will complete the questionnaire at baseline (first visit), four weeks later (second visit), and eight weeks later (third visit). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Suan-Zao-Ren Tang, Traditional Chinese Medicine, Methadone, Opiate dependence, Sleep