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NCT Number: NCT07081594

Investigating the Impact of Sex Hormones in Multiple Sclerosis

Emerging evidence indicates that females with MS experience worsened symptoms during the luteal phase (post ovulation) of the menstrual cycle when progesterone levels rise and estradiol fluctuate. The rapid hormonal swings may disrupt hypothalamic regulation, leading to an increase in body temperature - a well-established trigger for MS symptom exacerbation. These hormonal changes could also affect neuromuscular function, as estradiol and progesterone receptors are present in the nervous system and skeletal muscles.

Three critical aspects of motor rehabilitation are corticospinal excitability, motor learning, and fatigability. Previous research indicates that corticospinal excitability and the capacity to learn fine motor tasks fluctuate across menstrual cycles, indicating hormonal influences on neuroplasticity. However, it remains unclear how these hormonal fluctuations specifically affect corticospinal excitability, motor learning, and motor fatigability in females with MS. Understanding these relationships could significantly improve rehabilitation approaches. For example, pre-menopause females with MS may experience a more optimal state for neuroplasticity during the follicular phase of their cycles, therefore providing a potential window for greater rehabilitation efficacy.

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Key information

Conditions

Multiple Sclerosis Autoimmune Diseases Autoimmune Diseases of the Nervous System Demyelinating Autoimmune Diseases, CNS Demyelinating Diseases Immune System Diseases Nervous System Diseases

Age range

18 year and older

Sex eligibility

Female

Study type

Observational

Primary location

Shirley Ryan AbilityLab

Chicago, Illinois, 60611, United States

About this study

The objective of this project is to systematically examine how hormonal fluctuations pre-menopause influence corticospinal excitability, motor learning, and motor fatigability in females with MS. The study is structured around the following specific aims:

Aim 1: Quantify the effects of estradiol and progesterone levels on corticospinal excitability in pre- menopausal females with MS. We will elicit motor evoked potentials by cortical and subcortical stimulation of corticospinal axons using transcranial magnetic stimulation (TMS).

Aim 2: Evaluate how hormonal fluctuations across menstrual phases impact motor learning ability in pre-menopause females with MS. Participants will be asked to perform a finger sequence motor learning task using visual feedback. The task will be performed using a computer keyboard. Participants will be asked to copy the numerical sequence on a monitor in front of them that pertains to a number on the keyboard with their fingers. Participants will be given three different sequences with equivalent difficulty at each session to avoid carry-over effects between visits.

Aim 3: Determine the relationship between hormonal fluctuations and motor fatigability in pre-menopause females with MS. Participants will perform a maximal voluntary force (MVF). Participants will then be asked to pinch to 80% of their MVF, and maintain this hold for as long as possible1. The trial will end when the force drops below 40% MVF. Two trials in total will be performed. Average time to fatigue (40% MVF) and slope of the drop-off will be calculated as a measure of overall fatigue.

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • Age ≥18 years
  • Diagnosis of relapsing-remitting, primary progressive or secondary progressive MS with no minimum years since diagnosis
  • Stable disease modifying therapies for at least 6 months
  • Eumenorrheic females

Exclusion criteria

  • Another diagnosis (e.g., peripheral neuropathies or orthopedic)
  • Pregnancy as confirmed by urine test
  • Irregular menstrual cycles
  • Diagnosis of premenstrual dysphoric disorder or polycystic ovary syndrome
  • Taking antipsychotic medications / does not pass the TMS safety checklist

Treatment and study plan

Primary outcomes

  1. Corticospinal excitability

    Time frame: At 3 points during the individual's 1-month menstrual cycle, 1) Early Follicular 2) Late Follicular 3) Luteal

    Measuring the brain to muscle connection using transcranial magnetic stimulation - a non-invasive way to measure brain activity. Peak to Peak amplitude in mV is recorded

  2. Blood Draw

    Time frame: At 3 points during the individual's 1-month menstrual cycle, 1) Early Follicular 2) Late Follicular 3) Luteal

    To quantify estradiol and progesterone levels. Normative values of estradiol (E) and progesterone (P) per phase: early follicular (E: 125pmol/L; P: 0.38nmol/L), late follicular (E: 464pmol/L; P: 0.188nmol/L), luteal (E: 412pmol/L; P: 28.8nmol/L)

Secondary outcomes

  1. strength

    Time frame: At 3 points during the individual's 1-month menstrual cycle, 1) Early Follicular 2) Late Follicular 3) Luteal

    Measured by a pinch maximal voluntary contraction in lb-f

  2. Fatigue

    Time frame: At 3 points during the individual's 1-month menstrual cycle, 1) Early Follicular 2) Late Follicular 3) Luteal

    Measured with a pinch fatiguing task to estimate how quickly muscle of the hand fatigues. Measured in Seconds

  3. Motor Learning

    Time frame: At 3 points during the individual's 1-month menstrual cycle, 1) Early Follicular 2) Late Follicular 3) Luteal

    A visuomotor tracking task to measure difference between target trace and performed trace, measured in root mean squared error

Sponsors and collaborators

Lead sponsor

Milap Sandhu

Other

Registry information

Official study title

Investigating the Impact of Sex Hormones on Corticospinal Excitability, Motor Learning, and Fatigue in Females With Multiple Sclerosis

Important dates

Study start
2025
Primary completion
2027
Study completion
2029
First posted
Jul 23, 2025
Registry last updated
Mar 20, 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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