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NCT Number: NCT07166198

Mitigating Neural Hypoexcitability and Weakness During Disuse in Women

Clinical trial The goal of this clinical trial is to learn how muscle weakness and atrophy develop during short periods of arm immobilization and whether a type of exercise called cross-education can help reduce these effects in women at midlife.

The main questions it aims to answer are:

What changes happen in the nervous system that lead to weakness when a wrist is immobilized?

Can training the opposite arm help maintain muscle strength, muscle size, and nervous system function in the immobilized arm?

Researchers will compare women who have their wrist immobilized with or without opposite-arm resistance training.

Participants will:

Wear a wrist cast on one arm for 7 days

Complete strength training with the opposite arm or no training, depending on their group

Attend study visits for strength and nervous system testing

Have non-invasive tests (like magnetic brain stimulation, muscle recordings, and muscle imaging) to measure how the nervous system and muscle responds

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Key information

Conditions

Muscle Weakness Muscular Diseases Musculoskeletal Diseases Nervous System Diseases Neurologic Manifestations Neuromuscular Manifestations Pathologic Processes Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

40 year–65 year

Sex eligibility

Female

Study type

Interventional

Phase

Not applicable

Primary location

Neuromuscular Physiology Laboratory

Manhattan, Kansas, 66506, United States

Location status: Recruiting

Location contact

Joshua Carr, PhD

CONTACT

[email protected]

785-532-0700

About this study

This clinical trial employs a two-phase, parallel-group randomized controlled design targeting midlife women (ages 40-65), stratified by menopausal status. Participants will be randomized to either a cross-education training group (TRAIN) or a standard care control group (CONTROL).

Phase 1 (Immobilization and Cross-Education Intervention):

To induce rapid declines in neuromuscular function, participants will undergo unilateral wrist immobilization of the non-dominant arm using a hard cast for 7 days. During this period, the TRAIN group will complete three resistance training sessions with the non-immobilized arm, while the CONTROL group will remain inactive. The intervention protocol emphasizes maximal effort contractions. The protocol was developed from prior laboratory work and proof-of-concept interventions, with the goal of maximizing the cross-education response.

Phase 2 (Rehabilitation and Recovery):

Following cast removal, both groups will complete a 2-week standardized rehabilitation program (3 sessions per week) designed to restore wrist strength and function in the previously immobilized arm. Rehabilitation training includes progressive resistance exercise to target recovery of neuromuscular performance.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Women between 40-65 years of age
  • Baseline handgrip strength >16Kg

Exclusion criteria

  • Personal or family history of blood clots
  • Current use of anticoagulant medications
  • Neuromuscular or metabolic diseases (e.g., multiple sclerosis, diabetes)
  • Arthritis
  • Osteoporosis or osteopenia
  • History of myocardial infarction within the past year
  • Chronic pain ≥3/10 for ≥3 months
  • Uncontrolled hypertension (≥140/90 mmHg)
  • Upper extremity surgery within the past year
  • Use of assistive hand or arm device within the past year
  • Fall involving the upper extremities within the past year
  • Upper extremity injuries preventing safe participation
  • Current use of muscle relaxants, benzodiazepines, or similar drugs
  • Smoking within the past 6 months
  • History of drug or alcohol abuse within the past year
  • Severe anxiety or claustrophobia
  • Pregnancy (current or planned)
  • Allergies to medical adhesives
  • High risk of sarcopenia (per SARC-F)
  • Contraindications to TMS or MRI
  • Upper-body resistance training within the past 6 months
  • Inability/unwillingness to refrain from resistance training during study

Treatment and study plan

Wrist immobilization

Device

The wrist immobilization will use a medical device (wrist cast) to immobilize the left, non-dominant wrist for 7 days.

Resistance training

Behavioral

The cross-education intervention will consist of resistance training on the dominant hand.

Resistance training rehabilitation

Behavioral

The resistance training rehabilitation will occur for the non-dominant hand following the immobilization phase for all participants.

Primary outcomes

  1. Handgrip Strength

    Time frame: Baseline, immediately post-immobilization at 1 week, and post-rehabilitation at 3 weeks.

    Maximal handgrip strength (Kg) using an isometric handgrip dynamometer.

  2. Wrist Extension Strength

    Time frame: Baseline, immediately post-immobilization at 1 week, and post-rehabilitation at 3 weeks.

    Peak torque (Nm) of the wrist extensor muscles measured using isokinetic dynamometry

  3. Wrist Flexion Strength

    Time frame: Baseline, immediately post-immobilization at 1 week, and post-rehabilitation at 3 weeks.

    Peak torque (Nm) of the wrist flexor muscles measured using isokinetic dynamometry.

Secondary outcomes

  1. Wrist Muscle Cross-Sectional Area and Volume (CT Imaging)

    Time frame: Baseline, immediately post-immobilization at 1 week, and post-rehabilitation at 3 weeks.

    Muscle cross-sectional area (cm²) and volume (cm³) of the wrist extensors and flexors, assessed using computed tomography (CT). Scans will be obtained at standardized anatomical landmarks of the forearm. Cross-sectional images will be segmented and analyzed with imaging software to quantify muscle size. The primary outcome is mean muscle cross-sectional area, with muscle volume derived from consecutive slices. These measures provide indices of muscle size and atrophy/hypertrophy over time.

  2. Motor Evoked Potential (MEP) Amplitude

    Time frame: Baseline, immediately post-immobilization at 1 week, and post-rehabilitation at 3 weeks.

    Amplitude (mV) of motor-evoked potentials elicited by single-pulse TMS applied over the primary motor cortex of the left wrist and recorded from the extensor carpi radialis muscle. Larger amplitudes reflect greater corticospinal excitability.

  3. Short-Interval Intracortical Inhibition (SICI)

    Time frame: Baseline, immediately post-immobilization at 1 week, and post-rehabilitation at 3 weeks.

    Short-interval intracortical inhibition assessed by paired-pulse TMS with a subthreshold conditioning stimulus followed by a suprathreshold test stimulus at an interstimulus interval of 2-5 ms. Outcome is the percent suppression of MEP amplitude relative to unconditioned trials.

  4. Long-Interval Intracortical Inhibition (LICI)

    Time frame: Baseline, immediately post-immobilization at 1 week, and post-rehabilitation at 3 weeks.

    Assessed using paired-pulse TMS with a suprathreshold conditioning stimulus followed by a suprathreshold test stimulus at an interstimulus interval of 50-200 ms. LICI is quantified as the percent suppression of conditioned motor-evoked potential (MEP) amplitude relative to unconditioned MEPs.

  5. Intracortical Facilitation (ICF)

    Time frame: Baseline, immediately post-immobilization at 1 week, and post-rehabilitation at 3 weeks.

    Assessed using paired-pulse TMS with a subthreshold conditioning stimulus followed by a suprathreshold test stimulus at an interstimulus interval of 8-20 ms. ICF is quantified as the percent increase of conditioned MEP amplitude relative to unconditioned MEPs.

  6. Active Motor Threshold (AMT)

    Time frame: Baseline, immediately post-immobilization at 1 week, and post-rehabilitation at 3 weeks.

    Defined as the lowest TMS stimulus intensity (expressed as a percentage of maximum stimulator output) required to evoke MEPs ≥200 μV in at least 5 out of 10 consecutive trials during voluntary contraction of the target muscle at 10% of maximal effort. AMT reflects corticospinal excitability during an active state.

Other outcomes

  1. Menopausal Hormone Profile

    Time frame: Baseline

    Serum concentrations of estradiol, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) will be assessed from venous blood draws.

  2. Physical Activity Levels

    Time frame: Phase 1 (1 week immobilization) and Phase 2 (2-3 weeks rehabilitation)

    Physical activity levels, including daily step count and energy expenditure will be assessed using triaxial accelerometers (ActiGraph wGT3X-BT) worn on the dominant wrist.

Study contacts

Contact information is provided by the study sponsor or research team.

Joshua Carr, Ph.D.

CONTACT

[email protected]

785-532-0700

Julio Hernandez-Pavon, Ph.D.

CONTACT

[email protected]

Sponsors and collaborators

Lead sponsor

Kansas State University

Other

Collaborators

  • National Institute of General Medical Sciences (NIGMS)

Registry information

Acronym: MiND

Important dates

Study start
2026
Primary completion
2027
Study completion
2027
First posted
Sep 10, 2025
Registry last updated
Jun 10, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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