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

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

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.

Study Overview

• Status: Completed
• Conditions: Opiate Dependence
• Intervention / Treatment: Drug: Suan-Zao-Ren Tang; Drug: Suan-Zao-Ren Tang placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 2

Contacts and Locations

Study Locations

• Taiwan
  • Taoyuan, Taiwan, 325
    • Department of psychiatry, Armed Forces Tao-Yuan General Hospital, No.168 Zhong-Xing Road, Taoyuan, Taiwan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Suan-Zao-Ren Tang; 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; 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.
Placebo Comparator: Suan-Zao-Ren Tang placebo; 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; The Suan-Zao-Ren Tang placebo granules are prepared with 4 g starch inside the same colored and sized foil packages.

What is the study measuring?

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).

Collaborators and Investigators

• Sponsor: China Medical University, Taiwan

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): March 1, 2014

Study Registration Dates

• First Submitted: July 28, 2013
• First Submitted That Met QC Criteria: July 30, 2013
• First Posted (Estimate): August 1, 2013

Study Record Updates

• Last Update Posted (Estimate): March 18, 2014
• Last Update Submitted That Met QC Criteria: March 16, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Keywords: Sleep; Methadone; Traditional Chinese Medicine; Opiate dependence; Suan-Zao-Ren Tang
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Nervous System Diseases; Substance-Related Disorders; Sleep Wake Disorders; Narcotic-Related Disorders; Dyssomnias; Parasomnias; Opioid-Related Disorders
• Other Study ID Numbers: NSC 102-2320-B-039-024-