Exploring the Modulatory Role of Sex Hormones Along the Neuromechanical Axis in Females (EMRSHN)

EMRSHN 2: Exploring the Modulatory Role of Sex Hormones Along the Neuromechanical Axis in Females

The goal of this project is to test our central hypothesis that changes in sex hormone concentration result in changes to the basic elements of motor control - at multiple levels, from the musculotendinous unit to motor control circuitry. Under Aim 1 the investigator will determine the influence of sex hormone fluctuations on the muscle stretch reflex during active and passive states, and the time lag between hormone concentration changes and the reflex response. The investigator will use a technically simple assessment that could be implemented in the field. Under Aim 2 the investigator will determine the influence of sex hormone fluctuations on spinal motor neuron excitability using H-reflex as a probe and the simultaneous change in the muscle mechanics using muscle twitch response. Aims 1 & 2 will include a focus on the differential role of oral contraceptives. In Aim 3 the investigator will use paired-pulse transcranial magnetic stimulation during active contraction to determine the influence of sex hormone fluctuation.

Study Overview

• Status: Recruiting
• Conditions: Role of Sex Hormones Along the Neuromechanical Axis
• Intervention / Treatment: Device: Transcranial Magnetic Stimulation Device

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Pauline Phan, M.S.; Phone Number: 214-648-7954; Email: Pauline.Phan@UTSouthwestern.edu
• Study Contact Backup: Name: Maria P Kabamalan; Phone Number: 214-648-2755; Email: MariaPia.Kabamalan@UTSouthwestern.edu

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75390
      • Recruiting
      • UT Southwestern Medical Center
      • Contact: Pauline Phan, M.S.; Phone Number: 214-648-7954; Email: Pauline.Phan@UTSouthwestern.edu
      • Contact: Maria P Kabamalan; Phone Number: 214-648-2755; Email: MariaPia.Kabamalan@UTSouthwestern.edu
      • Principal Investigator: Yasin Dhaher, Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 39 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Females: ages 18-39 years, who are eumenorrheic (regular monthly cycles of 24-35 days) or on a stable hormonal contraceptive regimen for 6 months (oral, transdermal or vaginal), no history of pregnancy, moderately active (less than 7 hours of vigorous physical activity per week)
• Males: Ages 18-39

Exclusion Criteria:

• History of musculoskeletal or orthopedic injury of the spine, hip, knee, ankle or foot, history of neurological injury of the peripheral or central nervous system, current smoker, history of disordered eating, history of stress fracture in the lower limb, history of a connective tissue disorder (Marfan's syndrome, Ehlers-Danlos disease).
• For female participants only: Point of care screening for anemia will be completed, and individuals with hemoglobin levels <11.6 g/dl will be excluded from participating in the study.
• Specific exclusion criteria for TMS (male and female): pacemaker, metal implants in the head region, history of epilepsy or seizures, skull fractures or skull deficits, concussion within the last 6 months, unexplained recurring headaches, medications that lower seizure threshold, and pregnancy.
• Additional exclusion criteria for female participants: History of menstrual dysfunction (primary or secondary amenorrhea, oligomenorrhea, anovulatory cycles, polycystic ovarian disease), current or past pregnancy, started or stopped taking oral contraceptives within the previous 6 months, exercise vigorously more than 7 hours per week or currently participating in competitive level sports. The reason for excluding highly active or competitive athletes is due to the high rate of undiagnosed menstrual dysfunction in females of this population.
• This study will not include: adults unable to consent, Individuals who are not yet adults (infants, children, teenagers), pregnant women or prisoners.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TMS; Paired-pulse transcranial magnetic stimulation during active contraction to determine the influence of sex hormone fluctuations on cortical excitability in naturally cycling women.	Device: Transcranial Magnetic Stimulation Device; The TMS device electrically stimulates the intended parts of the brain. In this study, the investigator plan to target the part of the brain cortex that is responsible for the voluntary motion of the leg muscles, whose functions are under investigation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sex hormone fluctuations on muscle stretch reflex at relaxed and active states.	Blood draw for Estradiol, Progesterone, and Testosterone.	2 months
Tendon tap reflex testing.	The muscle reflex will be evoked by tapping the patellar tendon with a hammer instrumented with a load cell. The load cell instrumented hammer will allow us to quantify the reflex gain by normalizing the reflex EMG by the tap force.	2 months
Anterior knee laxity measurement.	To assess the joint's connective tissue response at varying points in the cycle, anterior knee laxity (AKL) will be measured with the knee arthrometer.	2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
H-reflex testing.	For the monosynaptic H-reflex testing, a stimulating bar bipolar electrode will be placed over the tibial nerve in the popliteal fossa with the anode positioned distally. The H-reflex and M-Wave will be recorded from the soleus muscle using surface EMG electrodes placed over the muscle belly at the myotendinous junction.	2 months
Polysynaptic reflex testing.	For polysynaptic reflex testing, stimulation will be applied behind the medial malleolus of the ankle to the distal tibial nerve using a Grass Instruments S48 Stimulator, a Grass SIU5 Stimulus Isolation Unit and a Grass Constant Current Unit. EMG recordings will be taken from the tibialis anterior muscle using self-adhesive surface electrodes. Data collection will include 20 series of 8 train pulses.	2 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sex hormone fluctuations on cortical excitability using transcranial magnetic stimulation (TMS).	MRI images will be acquired prior to the first TMS laboratory visit. The TMS coil will be positioned over the intersection of the central sulcus with the mid-sagittal plane using the subject's own anatomical MRI using an optical navigation system. Surface EMG will be recorded from muscles in the right leg. The paired-pulse paradigm isolates any modulatory influence of hormone concentration at cortex. With the subject seated with hip, knee, and ankle flexed at 90 degrees, TMS will be delivered to the leg area of the left motor cortex through using one of our TMS systems.	1 month
Ovulation testing.	Urine ovulation kit.	1 month

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Collaborators: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
• Investigators: Principal Investigator: Yasin Dhaher, Ph.D., UT Southwestern Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2019
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): May 1, 2024

Study Registration Dates

• First Submitted: April 22, 2019
• First Submitted That Met QC Criteria: May 9, 2019
• First Posted (Actual): May 13, 2019

Study Record Updates

• Last Update Posted (Actual): December 13, 2023
• Last Update Submitted That Met QC Criteria: December 12, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Sex Hormones
• Other Study ID Numbers: STU-2018-0192; 1R01AR069176-01A1 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes