The MUSE Study for Menopausal Arthralgia (MUSE)

The MUScle Strengthening Exercises and Estrogen (MUSE) Randomized Controlled Trial for Menopausal Arthralgia

The investigators plan to conduct a pilot 4-arm, randomized study comprising the following interventions: muscle strengthening exercises (MSE) alone, estrogen therapy (ET) alone, and a combination of MSE and ET, compared to usual care in women with menopausal arthralgia. The aim of this pilot study is to assess the feasibility, patient acceptability, and patient perspectives and logistics of delivering interventions, and practicability of outcome assessment tools in this 4-arm study over a 12-week period.

Study Overview

• Status: Recruiting
• Conditions: Joint Pain; Arthralgia; Menopause; Perimenopausal Disorder; Postmenopausal Disorder
• Intervention / Treatment: Behavioral: Exercise training; Drug: Menopausal hormone therapy; Combination product: Menopausal hormone therapy + exercise training

Detailed Description

Recruited participants will be randomized to one of the following arms for 12 weeks: usual clinical care, 17b-Estradiol/progesterone (ET) only, Muscle strengthening exercises (MSE) only, combination of MSE plus ET. All participants will be assessed at Baseline and at 12 weeks.

Estrogen therapy (ET): Participants would apply 17b-estradiol (1.25-2.5 gms/daily) gel transdermally to joints and muscles most affected by arthralgia for 12 weeks. Participants with intact uteri would also be issued micronized Progesterone 200mg tablets to be taken orally for 12 days each month. Medications would be dispensed by the National University Hospital (NUH) pharmacy.

Muscle strengthening exercises (MSE) Exercises would be demonstrated in person by qualified staff physiotherapists. All Participants would be given a standard strength training protocol, with additional tailored exercises targeting their pain conditions, abilities and personal preferences. Exercises would focus on upper and lower body strength generally. Participants would be encouraged to exercise every day, alternating between upper and lower body strength training following the curated exercises. Exercise regimes would be reinforced through weekly reminders, and posts through social media.

MSE plus ET: Participants randomized to combination of would have both treatments administered at the same time within the same intervention period of 12 weeks. In other words, participants would be instructed to do the curated exercises and apply 17b-estradiol (1.25-2.5 gms/daily) gel trans-dermally with micronized progesterone oral tablets.

Usual care: Participants would continue their usual daily routines and come for outcome assessments at baseline and 12 weeks.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Eu-Leong Yong, PhD; Phone Number: 67724278; Email: obgyel@nus.edu.sg

Study Locations

• Singapore
  • Singapore, Singapore
    • Recruiting
    • National University Hospital
    • Contact: Eu-Leong Yong

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

INCLUSION CRITERIA:

1. Patients with muscle stiffness and joint discomfort in various sites, including hands, knees, back, hips, and/or shoulders. Patients with pain in only one isolated joint would not be accepted.
2. Arthralgia symptoms with onset, or has become worse, over the perimenopausal or early postmenopausal period (within 5 years of the menopause).

3. Women should be at the menopause transition, less than or equal to 59 years old at the time of enrollment, or within 5 years of menopause whichever is earlier.

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4. Arthralgia for at least 3 months (pain lasting beyond normal injury healing period)
5. Community-dwelling and able to ambulate independently.

EXCLUSION CRITERIA:

1. History of thrombo-embolic diseases, strokes, ischemic heart disease, dementia or psychiatric disorders, active liver disease or renal impairment, severe hyperlipidemia, gout, thyroid disease, systemic lupus erythematosus, rheumatoid arthritis, or other chronic inflammatory conditions.
2. Pregnancy
3. Non-adherence to national guidelines for breast cancer screening
4. High risk for breast cancer
5. Any joint surgery within the last 6 months
6. Severe obesity: BMI>35
7. Migraine with aura
8. Poorly controlled diabetes
9. Use of any form of female hormone supplementation within the past 12 weeks.
10. High venous thromboembolism risk
11. Current cholecystitis, fibroids, or undiagnosed abnormal uterine bleeding.
12. Current smoker.
13. History of endometrial, ovarian, peritoneal, cervical, breast or endocrine-dependent cancers.
14. Receiving treatment for any form of cancer.
15. History of fragility bone fractures within the 2 years.
16. Any other cognitive, musculoskeletal, neurological, and cardiorespiratory condition affecting one's ability to participate in the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Exercise; Curated exercises designed to address specific muscle groups and joints that are painful and problematic. Exercises would focus on upper and lower body strength generally. It is anticipated that participants ideally should exercise at least 3 times per week based on the strength training prescription. They could potentially exercise everyday, alternating between upper and lower body strength training.	Behavioral: Exercise training; Exercises would focus on upper and lower body strength generally. It is anticipated that the participants ideally should exercise at least 3 times per week based on the strength training prescription. They could potentially exercise everyday, alternating between upper and lower body strength training. In all, there are up to 1-2 in-person therapy sessions and home sessions at least 3 times per week.
Experimental: Menopausal hormone therapy; Menopausal hormone therapy comprising: 17beta-estradiol topical gel (1.25-2.5 gms) applied daily, and micronized Progesterone 200mg daily for 12 days each month.	Drug: Menopausal hormone therapy; Apply 17 beta-Estradiol topical gel (1.25-2.5 gms) daily Ingest Micronized Progesterone 200mg daily for 12 days each month
Experimental: Combination of exercise and menopausal hormone therapy; Curated exercises designed to address specific muscle groups and joints that are painful and problematic.Exercises would focus on upper and lower body strength generally. It is anticipated that the participants ideally should exercise at least 3 times per week based on the strength training prescription. They could potentially exercise everyday, alternating between upper and lower body strength training.; Menopausal hormone therapy comprising: 17beta-estradiol topical gel (1.25-2.5 gms) applied daily, and micronized Progesterone 200mg daily for 12 days each month.	Combination product: Menopausal hormone therapy + exercise training; Apply 17 beta-Estradiol topical gel (1.25-2.5 gms) daily and Ingest Micronized Progesterone 200mg daily for 12 days each month; Exercises would focus on upper and lower body strength generally. It is anticipated that patients ideally should exercise at least 3 times per week based on the strength training prescription. They could potentially exercise everyday, alternating between upper and lower body strength training. In all, there are up to 1-2 in-person therapy sessions and home sessions at least 3 times per week.
No Intervention: Standard care; Standard care will be provided.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative changes in perceived arthralgia at the end of intervention	Relative changes in perceived arthralgia with the 10-item Örebro Musculoskeletal Pain Screening Questionnaire (Short Form) would be the pre-specified primary outcome parameter. Participants would be asked to rank each item on a 11-point scale from 0 to 10.	After 12 weeks of intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Handgrip strength (kg)	Handgrip strength (kg) will be assessed twice on each arm, using the Jamar dynamometer.	After 12 weeks of intervention
Changes in isokinetic knee extension strength (degree/second)	The knee extension strength test will be conducted using the isokinetic dynamometry with Biodex, and measured in degree/second.	After 12 weeks of intervention
Changes in physical performance using the Physical Performance Battery	The investigators will use a modified version of the lower-extremity performance tests conducted in the Established Populations for the Epidemiologic Studies of the Elderly, wherein scores from four tests will be added to form a continuous score ranging from 0 to 4.	After 12 weeks of intervention
Changes in associated menopausal symptoms using the Menopause Rating Scale (MRS)	Menopausal symptoms will be assessed using the Menopause Rating Scale (MRS), comprising 11 menopausal symptoms. Each symptom will be scored from 0-4 (none, mild, moderate, severe, and extremely severe).	After 12 weeks of intervention
Changes in sleep quality using the Pittsburgh Sleep Quality Index (PSQI)	The Pittsburgh Sleep Quality Index will be used to assess perceived sleep habits in the past month, with a maximum score of 21 points.	After 12 weeks of intervention
Changes in anxiety symptoms using the GAD-7	Anxiety symptoms will be assessed by the General Anxiety Disorder Scale (GAD-7), and scoring ranges from 0 to 21 points.	After 12 weeks of intervention
Changes in depression symptoms using the CES-D	Depressive symptoms will be assessed using the Center for Epidemiologic Studies for Depression Scale (CES-D). The maximum score is 60.	After 12 weeks of intervention
Changes in perceived quality of life using the SF-12.	The 12-Item Short Form Survey (SF-12) will be used to assess quality of life.	After 12 weeks of intervention
Changes in verbal memory measured using the Hopkins Verbal Learning Test	The Hopkins Verbal Learning Test will be used to assess delays in recall and retention of 12 words.	After 12 weeks of intervention
Changes in insulin resistance using HOMA-IR	Fasting blood glucose and insulin will be measured to obtain the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR).	After 12 weeks of intervention

Collaborators and Investigators

• Sponsor: National University Hospital, Singapore

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2024
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: April 11, 2024
• First Submitted That Met QC Criteria: July 26, 2024
• First Posted (Actual): July 31, 2024

Study Record Updates

• Last Update Posted (Actual): July 31, 2024
• Last Update Submitted That Met QC Criteria: July 26, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Exercise; Randomized controlled trial; Muscle strength; Menopausal hormone therapy; Midlife women
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Joint Diseases; Musculoskeletal Diseases; Arthralgia; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormones
• Other Study ID Numbers: 2023/00727

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