A Randomized Controlled Trial of Auricular Acupressure in Treating Estazolam-dependent Insomnia (ESAAEDI)

A Randomized Controlled Trial of Auricular Acupressure on Reduction of Estazolam in Patients With Insomnia

Insomnia is a disorder characterized by difficulties in falling asleep, maintaining sleep or waking up too early, and impairment of daytime functioning. Drug-dependent insomnia refers to insomnia patients taking sedatives and sleeping pills regularly for a long period of time, and becoming psychologically and physiologically dependent on them. In many countries, auricular acupressure (AA) has attracted growing attention as a complementary or alternative treatment for insomnia; however, there is a lack of rigorous randomized, controlled studies evaluating AA specifically for estazolam-dependent insomnia. Our proposed trial aims to assess the therapeutic effect of AA on estazolam-dependent insomnia.

Study Overview

• Status: Not yet recruiting
• Conditions: Estazolam-dependent Insomnia
• Intervention / Treatment: Drug: Conventional dosage reduction; Procedure: Auricular acupressure; Procedure: Sham auricular acupressure

Detailed Description

This study is a randomized, single-blinded, three-arm controlled trial. No less than 120 participants will be randomized into one of three groups: AA group, sham auricular acupressure (SAA) group, and conventional dosage reduction group. All treatments will be administered for 4 weeks, with a follow-up period of 1 month. The primary clinical outcomes will be estazolam dosing and reduction rates, serum gamma-aminobutyric acid (GABA) and cortisol (CORT) levels. Secondary outcomes will concern the Pittsburgh sleep quality index (PSQI) and Benzodiazepine Withdrawal Symptom Questionnaire (BWSQ). Both intention-to-treat and per-protocol analyses will be performed, with significance level determined as 5%.

• Study Type: Interventional
• Enrollment (Estimated): 108
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Qiqi Wu; Phone Number: +8617826867387; Email: wuqiqi_0722@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Meet the diagnostic criteria for insomnia;
• Meet the diagnostic criteria for hypnotic drug-dependent insomnia;
• Regularly taking estazolam tablets for more than 2 months, and need to stop the medication;
• The dependent dosage of estazolam is 1mg, and withdrawal reaction occurs when the dosage is less than 1mg;
• PSQI score ≥ 7 (defined as "poor sleep quality", PSQI ≥ 7 is used as the reference threshold for judging sleep quality problems);
• Sign the informed consent.

Exclusion Criteria:

• Patients with cognitive disorders caused by cerebrovascular diseases, psychiatric disorders, and so on;
• Patients with serious heart, liver, kidney and blood system diseases;
• Patients with psychiatric illness/drug abuse (including alcohol);
• Patients who cannot cooperate with treatment, observation and evaluation.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Conventional dosage reduction group; The drug reduction method of estazolam tablets (Shanghai Xinyi Pharmaceutical Co., Ltd., Shanghai, China, State Drugs Administration License No.: H31020644, 1 mg) will be given, with a starting dose of 1 mg, that is, the dosage of estazolam will be reduced by 25% (0.25mg) every week until the dosage will be stopped completely on the premise of no aggravation of insomnia symptoms.	Drug: Conventional dosage reduction; The doctor will guide patients to adjust medication dosage once a week in the outpatient clinic. When patients experience withdrawal reactions such as worsening insomnia or anxiety symptoms due to drug reduction, they will be returned to the oral dose before the current reduction, and the dosage will be reduced again after evaluation in the next reduction cycle. The treatment for 4 weeks is one course and 1 course of treatment is required totally.; Other Names: Estazolam reduction
Experimental: Auricular acupressure group; Auricular acupressure therapy will be added based on the estazolam reduction method in the control group. The specific auricular points to be treated are Shenmen (TF4), Sympathetic (AH6), Endocrine (CO18), Heart (CO15), Liver (CO12) and Kidney (CO10). During the treatment, the acupuncturist will use a metal probe to identify the auricular points and ask the patients if they experience "deqi" sensations such as heat, numbness, distension, or pain. Once the auricular points have been confirmed, the ear will be disinfected using a 75% ethanol solution and dried using a sterile dry cotton ball. The acupuncturist will then hold the ear in place with their left hand while using their right hand to manipulate a tweezer and apply tape (0.5 x 0.5 cm) with vaccaria (Suzhou Konakang Medical Instrument Co., LTD., Suzhou, China) to the selected auricular point.	Procedure: Auricular acupressure; Auricular acupressure is a non-pharmacological therapy that involves applying acupressure on the surface of points in different parts of the ear. One side of the auricular acupoints will be treated first and the tapes will be kept in place for 3 days. On the fourth day, the tapes on the ear will be removed and new tapes will be applied to the opposite side of the ear. The purpose of replacing tapes is to reduce the adverse events (AEs) that may be caused by long-term stimulation unilaterally. In addition, the participants will be informed to press the tapes by themselves for 3 to 5 minutes vertically and appropriately to achieve the sensation, with a duration of 4 to 5 times a day. The treatment will last for 4 weeks, and the follow-up will be done after 1 month.
Sham Comparator: Sham auricular acupressure group; Based on the estazolam reduction method in the control group, the acupuncturist will place the same skin-colored adhesive tapes without vaccaria on the auricular points, but these tapes will not be pressed during treatment.	Procedure: Sham auricular acupressure; Based on the estazolam reduction method in the control group, the acupuncturist will place the same skin-colored adhesive tapes without vaccaria on the auricular points, but these tapes will not be pressed during treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Estazolam Dosing and Reduction Rates	The amount of drug taken by patients will be assessed.The rate of dosage reduction will be observed. Estazolam reduction rate = (pre-treatment Estazolam dose - post-treatment Estazolam dose)/pre-treatment Estazolam dose x 100%.	Estazolam dosing will be assessed before treatment，1, 2, 3, and 4 weeks after treatment，1 month after follow-up visiting. The rate of dosage reduction will be observed 4weeks after treatment，1 month after follow-up visiting
Serum Gamma-aminobutyric acid and Cortisol Levels	The method of enzyme-linked immunosorbent assay (ELISA) will be used. 4 ml of venous blood will be extracted from the subjects, and will be added anticoagulant. After that, the samples will be centrifuged at 3000 r/min to separate upper serum and preserved in a refrigerator at -80℃, according to the kit instructions.	Venous blood samples will be drawn twice from each patient at 8:00-9:00 in the morning 1 day before treatment and 1 day after the end of treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pittsburgh Sleep Quality Index	The Pittsburgh Sleep Quality Index is a self-rated questionnaire used to assess sleep quality and disturbances over a 1-month period. It comprises 19 self-rated items and five other-rated items. The scores for the 19 self-rated items and five other-rated items are not included in the total score. Except for the first item, the remaining 18 items include the seven following subscales: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficacy, sleep disturbances, use of sleeping medication, and daytime dysfunction. Each subscale is rated from 0 to 3, and the accumulated scores of the seven subscales constitute the total score of the PSQI (0-21), where 7 is the threshold value of the sleep quality problem. A higher score indicates more severe sleep disorders.	Baseline, 4 weeks after treatment commencement, and the 1-month follow-up
Benzodiazepine Withdrawal Symptom Questionnaire	A self-report questionnaire is described which records the main symptoms experienced during withdrawal from benzodiazepines in pharmacologically dependent patients. The questionnaire consists of 20 items	Baseline, 4 weeks after treatment commencement, and the 1-month follow-up

Collaborators and Investigators

• Sponsor: Wenzhou Central Hospital
• Investigators: Principal Investigator: Qiqi Wu, Wenzhou Central Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2024
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): June 30, 2025

Study Registration Dates

• First Submitted: February 5, 2024
• First Submitted That Met QC Criteria: February 5, 2024
• First Posted (Actual): February 14, 2024

Study Record Updates

• Last Update Posted (Actual): February 14, 2024
• Last Update Submitted That Met QC Criteria: February 5, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: randomized controlled trial; insomnia; auricular acupressure; estazolam; drug-dependent; estazolam-dependent insomnia
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Sleep Initiation and Maintenance Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Tranquilizing Agents; Psychotropic Drugs; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Anticonvulsants; Estazolam
• Other Study ID Numbers: Y2023213

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No