the Effects of Different Therapy Regimens on Menopausal Sleep Disorders

A Prospective Randomized Controlled Study of the Effects of Different Therapy Regimens on Menopausal Sleep Disorders

Sleeping disorders are one of the most common menopausal symptoms, which seriously affect health and life quality of perimenopausal women. Menopausal hormone therapy is an effective treatment for menopausal symptoms, meanwhile, traditional Chinese medicine is also effective to some extent. This prospective randomized controlled study plan to compare the effects of different therapy regimens, including Tibolone and Xiangshao granules, on menopausal sleep disorders.

Study Overview

• Status: Not yet recruiting
• Conditions: Sleep Disorder; Menopause
• Intervention / Treatment: Drug: Tibolone; Drug: Xiangshao granules; Drug: Tibolone plus Xiangshao granules

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Rong Chen, Professor; Phone Number: 010-13811030947; Email: chenrongpumch@163.com
• Study Contact Backup: Name: Lingjin Yang; Phone Number: 010-15650795133; Email: yanglingjin0803@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• women aged 40-60
• natural menopause for 1-10 years
• PSQI score >=11 points
• improved K-score>=14 points
• able to independently sign informed consent forms

Exclusion Criteria:

• Vaginal bleeding of unknown cause
• Known or suspected breast cancer and other sex hormone dependent tumors
• Active venous or arterial thromboembolic disease within past 6 months
• Have used sex hormone or traditional Chinese medicine/botanical drugs that affect menopausal symptoms within the past month
• Have used anti anxiety, depression drugs or sedative hypnotics within the past month
• Patients with anxiety or depression above moderate level
• Severe liver or kidney dysfunction, with transaminase or creatinine level exceeding twice of the normal value
• BMI ≥ 28 kg/m2
• Allergies to research drugs
• Other situations that doctor deems unsuitable to participate in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tibolone; take Tibolone 1.25mg/day orally for 8 weeks	Drug: Tibolone; 1.25mg po qd
Experimental: Xiangshao granules; take Xiangshao granules orally 3 times a day, 4g each time	Drug: Xiangshao granules; 4g po tid
Experimental: Tibolone plus Xiangshao granules; take Tibolone 1.25mg/day and Xiangshao granules 3 times a day, 4g each time orally for 8 weeks	Drug: Tibolone plus Xiangshao granules; Tibolone 1.25mg po qd plus Xiangshao granules 4g po tid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sleep diary	Sleep diary is recorded by study participants daily.	V0(screening period), V1（dsy 1）, V2(week 4), V3(week 8)
Polysomnography (PSG)	Extract PSG EEG data: record time, bed time, sleep time, awakening time, rapid eye movement sleep time (REM), non rapid eye movement sleep time (NREM), non rapid eye movement sleep phase 1 (N1), non rapid eye movement sleep phase 2 (N2), non rapid eye movement sleep phase 3 (N3), total sleep time (TST), sleep latency (SL), wake after sleep onset (WASO), sleep efficiency (SE).	V0(screening period), V3(week 8)
Pittsburgh Sleep QualityIndex questionnaire (PSQI questionnaire)	The total score of PSQI questionnaire is 0-21 points. Normal sleep quality is defined as less than 11 points.	V0(screening period), V2(week 4), V3(week 8)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improved Kupperman score	The total score of improved K score is graded into four levels: normal(<7), mild(7-14), moderate(15-29), severe(>30).	V0(screening period), V2(week 4), V3(week 8)
Menopause-specific Quality of Life Scale	Evaluate vasomotor symptoms, psychological and emotional symptoms, physical symptoms and sexual activity symptoms. Choose a level from "0-6" based on the degree to which this symptom affects subject. ''0'' means it doesn't affect subject at all; ''6'' indicates extreme impact on subject.	V0(screening period), V2(week 4), V3(week 8)
Self-Rating Anxiety Scale	Assess anxiety level over the past two weeks. The evaluation adopts a 1-4 scoring system, where the scores of 20 questions are added together to obtain the total score. The total score is multiplied by 1.25 and rounded to the nearest whole number to obtain the standard score. The cut-off value of SAS standard score is 50 points, with a score of 50-59 indicating mild anxiety, 60-69 indicating moderate anxiety, and a score above 70 indicating severe anxiety.	V0(screening period), V2(week 4), V3(week 8)
Center for Epidemiological Survey Depression Scale (CES Depression Scale)	The total score of CES-D is graded into three levels: asymptomatic(<15), possible depressive symptoms(16-19), existed depressive symptoms(≥20)	V0(screening period), V2(week 4), V3(week 8)

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Investigators: Study Director: Rong Chen, Professor, Peking Union Medical College Hospital

Publications and helpful links

General Publications

• Riemann D, Baglioni C, Bassetti C, Bjorvatn B, Dolenc Groselj L, Ellis JG, Espie CA, Garcia-Borreguero D, Gjerstad M, Goncalves M, Hertenstein E, Jansson-Frojmark M, Jennum PJ, Leger D, Nissen C, Parrino L, Paunio T, Pevernagie D, Verbraecken J, Weess HG, Wichniak A, Zavalko I, Arnardottir ES, Deleanu OC, Strazisar B, Zoetmulder M, Spiegelhalder K. European guideline for the diagnosis and treatment of insomnia. J Sleep Res. 2017 Dec;26(6):675-700. doi: 10.1111/jsr.12594. Epub 2017 Sep 5.
• Moline ML, Broch L, Zak R, Gross V. Sleep in women across the life cycle from adulthood through menopause. Sleep Med Rev. 2003 Apr;7(2):155-77. doi: 10.1053/smrv.2001.0228.
• Gold EB, Sternfeld B, Kelsey JL, Brown C, Mouton C, Reame N, Salamone L, Stellato R. Relation of demographic and lifestyle factors to symptoms in a multi-racial/ethnic population of women 40-55 years of age. Am J Epidemiol. 2000 Sep 1;152(5):463-73. doi: 10.1093/aje/152.5.463.
• Kaplan KA, Hardas PP, Redline S, Zeitzer JM; Sleep Heart Health Study Research Group. Correlates of sleep quality in midlife and beyond: a machine learning analysis. Sleep Med. 2017 Jun;34:162-167. doi: 10.1016/j.sleep.2017.03.004. Epub 2017 Mar 27.
• Kenemans P, Speroff L; International Tibolone Consensus Group. Tibolone: clinical recommendations and practical guidelines. A report of the International Tibolone Consensus Group. Maturitas. 2005 May 16;51(1):21-8. doi: 10.1016/j.maturitas.2005.02.011.
• Jiang XR, Ren L, Li CR. [Effect of Electroacupuncture on Hypothalamus-Pituitary-Ovary (HPO) Axis in Rats with Peri-menopausal Depression]. Zhen Ci Yan Jiu. 2017 Feb 25;42(1):45-9. Chinese.
• Chen R, Tang R, Zhang S, Wang Y, Wang R, Ouyang Y, Xie X, Liu H, Lv S, Shi H, Zhang Y, Xie M, Luo Y, Yu Q. Xiangshao granules can relieve emotional symptoms in menopausal women: a randomized controlled trial. Climacteric. 2021 Jun;24(3):246-252. doi: 10.1080/13697137.2020.1820476. Epub 2020 Oct 5.

Helpful Links

• Guideline for the evaluation and treatment of insomnia in Chinese adults(2017)
• The 2023 Chinese menopause symptom management and menopausal hormone therapy guidelines
• Curative Effect Analysis on Xiang Shao Particle in the Treatment of Women Perimenopausal Syndrome
• Efficacy and safety of Jingqianping granule in treatment of 403 cases of the liver-qi invasion of premenstrual syndrome with multicentre, random,double-blind and double simulation and control method

Study record dates

Study Major Dates

• Study Start (Estimated): December 30, 2023
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): September 30, 2025

Study Registration Dates

• First Submitted: October 16, 2023
• First Submitted That Met QC Criteria: October 31, 2023
• First Posted (Actual): November 7, 2023

Study Record Updates

• Last Update Posted (Actual): January 2, 2024
• Last Update Submitted That Met QC Criteria: December 22, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Sleep Wake Disorders; Parasomnias; Physiological Effects of Drugs; Antihypertensive Agents; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Estrogen Receptor Modulators; Androgen Antagonists; Anabolic Agents; Tibolone
• Other Study ID Numbers: menopausal sleep disorders

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