Mitigating Neural Hypoexcitability and Weakness During Disuse in Women

Overview

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

Detailed description

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.

Interventions

• Device Wrist immobilization
  The wrist immobilization will use a medical device (wrist cast) to immobilize the left, non-dominant wrist for 7 days.
• Behavioral Resistance training
  The cross-education intervention will consist of resistance training on the dominant hand.
• Behavioral Resistance training rehabilitation
  The resistance training rehabilitation will occur for the non-dominant hand following the immobilization phase for all participants.

Primary outcome measures

• Handgrip Strength [Time frame: Baseline, immediately post-immobilization at 1 week, and post-rehabilitation at 3 weeks.]
• Wrist Extension Strength [Time frame: Baseline, immediately post-immobilization at 1 week, and post-rehabilitation at 3 weeks.]
• Wrist Flexion Strength [Time frame: Baseline, immediately post-immobilization at 1 week, and post-rehabilitation at 3 weeks.]

Secondary outcome measures (6)

• Wrist Muscle Cross-Sectional Area and Volume (CT Imaging) [Time frame: Baseline, immediately post-immobilization at 1 week, and post-rehabilitation at 3 weeks.]
• Motor Evoked Potential (MEP) Amplitude [Time frame: Baseline, immediately post-immobilization at 1 week, and post-rehabilitation at 3 weeks.]
• Short-Interval Intracortical Inhibition (SICI) [Time frame: Baseline, immediately post-immobilization at 1 week, and post-rehabilitation at 3 weeks.]
• Long-Interval Intracortical Inhibition (LICI) [Time frame: Baseline, immediately post-immobilization at 1 week, and post-rehabilitation at 3 weeks.]
• Intracortical Facilitation (ICF) [Time frame: Baseline, immediately post-immobilization at 1 week, and post-rehabilitation at 3 weeks.]
• Active Motor Threshold (AMT) [Time frame: Baseline, immediately post-immobilization at 1 week, and post-rehabilitation at 3 weeks.]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Basic science

Study locations

United States · 1 center

• Neuromuscular Physiology Laboratory — Manhattan

Identifiers

NCT: NCT07166198 · 12503 · 5P20GM113109-09

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗