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出境医 / 临床实验 / Exploring the Modulatory Role of Sex Hormones Along the Neuromechanical Axis in Females (EMRSHN)

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

Study Description
Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Role of Sex Hormones Along the Neuromechanical Axis Device: Transcranial Magnetic Stimulation Device Not Applicable

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: EMRSHN 2: Exploring the Modulatory Role of Sex Hormones Along the Neuromechanical Axis in Females
Actual Study Start Date : April 12, 2019
Estimated Primary Completion Date : April 2022
Estimated Study Completion Date : April 2022
Arms and Interventions
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.

Outcome Measures
Primary Outcome Measures :
  1. Sex hormone fluctuations on muscle stretch reflex at relaxed and active states. [ Time Frame: 2 months ]
    Blood draw for Estradiol, Progesterone, and Testosterone.

  2. Tendon tap reflex testing. [ Time Frame: 2 months ]
    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.

  3. Anterior knee laxity measurement. [ Time Frame: 2 months ]
    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.


Secondary Outcome Measures :
  1. H-reflex testing. [ Time Frame: 2 months ]
    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. Polysynaptic reflex testing. [ Time Frame: 2 months ]
    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.


Other Outcome Measures:
  1. Sex hormone fluctuations on cortical excitability using transcranial magnetic stimulation (TMS). [ Time Frame: 1 month ]
    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.

  2. Ovulation testing. [ Time Frame: 1 month ]
    Urine ovulation kit.


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years to 39 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.
Contacts and Locations

Contacts
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Contact: Pauline Phan, M.S. 214-648-7954 Pauline.Phan@UTSouthwestern.edu
Contact: Maria P Kabamalan 214-648-2755 MariaPia.Kabamalan@UTSouthwestern.edu

Locations
Layout table for location information
United States, Texas
UT Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390
Contact: Pauline Phan, M.S.    214-648-7954    Pauline.Phan@UTSouthwestern.edu   
Contact: Maria P Kabamalan    214-648-2755    MariaPia.Kabamalan@UTSouthwestern.edu   
Principal Investigator: Yasin Dhaher, Ph.D.         
Sponsors and Collaborators
University of Texas Southwestern Medical Center
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Investigators
Layout table for investigator information
Principal Investigator: Yasin Dhaher, Ph.D. UT Southwestern Medical Center
Tracking Information
First Submitted Date  ICMJE April 22, 2019
First Posted Date  ICMJE May 13, 2019
Last Update Posted Date December 4, 2020
Actual Study Start Date  ICMJE April 12, 2019
Estimated Primary Completion Date April 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 9, 2019)
  • Sex hormone fluctuations on muscle stretch reflex at relaxed and active states. [ Time Frame: 2 months ]
    Blood draw for Estradiol, Progesterone, and Testosterone.
  • Tendon tap reflex testing. [ Time Frame: 2 months ]
    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.
  • Anterior knee laxity measurement. [ Time Frame: 2 months ]
    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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 9, 2019)
  • H-reflex testing. [ Time Frame: 2 months ]
    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.
  • Polysynaptic reflex testing. [ Time Frame: 2 months ]
    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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: May 9, 2019)
  • Sex hormone fluctuations on cortical excitability using transcranial magnetic stimulation (TMS). [ Time Frame: 1 month ]
    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.
  • Ovulation testing. [ Time Frame: 1 month ]
    Urine ovulation kit.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Exploring the Modulatory Role of Sex Hormones Along the Neuromechanical Axis in Females
Official Title  ICMJE EMRSHN 2: Exploring the Modulatory Role of Sex Hormones Along the Neuromechanical Axis in Females
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Role of Sex Hormones Along the Neuromechanical Axis
Intervention  ICMJE 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.
Study Arms  ICMJE 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.
Intervention: Device: Transcranial Magnetic Stimulation Device
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 9, 2019)
70
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 2022
Estimated Primary Completion Date April 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 39 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Pauline Phan, M.S. 214-648-7954 Pauline.Phan@UTSouthwestern.edu
Contact: Maria P Kabamalan 214-648-2755 MariaPia.Kabamalan@UTSouthwestern.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03947684
Other Study ID Numbers  ICMJE STU-2018-0192
1R01AR069176-01A1 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Yasin Dhaher, University of Texas Southwestern Medical Center
Study Sponsor  ICMJE University of Texas Southwestern Medical Center
Collaborators  ICMJE National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Investigators  ICMJE
Principal Investigator: Yasin Dhaher, Ph.D. UT Southwestern Medical Center
PRS Account University of Texas Southwestern Medical Center
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP