Multiple SclerosisNCT07081594
Investigating the Impact of Sex Hormones in Multiple Sclerosis
An observational study of Multiple Sclerosis, run by Milap Sandhu at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Multiple Sclerosis
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Aug 2025to Mar 2029
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Study population: Persons with menstrual cycles and any form of multiple sclerosis
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Investigating the Impact of Sex Hormones on Corticospinal Excitability, Motor Learning, and Fatigue in Females With 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.
Read the detailed description
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.
- Conditions
- Multiple Sclerosis
- Keywords
- Multiple Sclerosis, Sex hormones, menstrual cycle
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Pre-Menopausal Women | Naturally cycling women with multiple sclerosis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Corticospinal excitability
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
Measured: At 3 points during the individual's 1-month menstrual cycle, 1) Early Follicular 2) Late Follicular 3) Luteal
Blood Draw
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)
Measured: At 3 points during the individual's 1-month menstrual cycle, 1) Early Follicular 2) Late Follicular 3) Luteal
Secondary outcomes (3)
strength
Measured by a pinch maximal voluntary contraction in lb-f
Measured: At 3 points during the individual's 1-month menstrual cycle, 1) Early Follicular 2) Late Follicular 3) Luteal
Fatigue
Measured with a pinch fatiguing task to estimate how quickly muscle of the hand fatigues. Measured in Seconds
Measured: At 3 points during the individual's 1-month menstrual cycle, 1) Early Follicular 2) Late Follicular 3) Luteal
Motor Learning
A visuomotor tracking task to measure difference between target trace and performed trace, measured in root mean squared error
Measured: At 3 points during the individual's 1-month menstrual cycle, 1) Early Follicular 2) Late Follicular 3) Luteal
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2025
- Study start28 Aug 2025
- Primary completionMar 2027 (estimated)
- Study completionMar 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 14 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Milap Sandhu
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Milap Sandhu, Shirley Ryan AbilityLab
- Investigators
- Milap Sandhu, PT, PhD, Principal investigator, Shirley Ryan AbilityLab
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07081594
- Sponsor's protocol ID
- STU00224323
- Status last verified
- Mar 2026
- First submitted
- 17 Jun 2025
- Last updated
- 20 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-Identified data will be available after completion of the study upon request
Publications
Christogianni A, O'Garro J, Bibb R, Filtness A, Filingeri D. Heat and cold sensitivity in multiple sclerosis: A patient-centred perspective on triggers, symptoms, and thermal resilience practices. Mult Scler Relat Disord. 2022 Nov;67:104075. doi: 10.1016/j.msard.2022.104075. Epub 2022 Jul 25.
PubMed 35963205Karim HT, Huppert TJ, Erickson KI, Wollam ME, Sparto PJ, Sejdic E, VanSwearingen JM. Motor sequence learning-induced neural efficiency in functional brain connectivity. Behav Brain Res. 2017 Feb 15;319:87-95. doi: 10.1016/j.bbr.2016.11.021. Epub 2016 Nov 11.
PubMed 27845228Casamento-Moran A, Mooney RA, Chib VS, Celnik PA. Cerebellar Excitability Regulates Physical Fatigue Perception. J Neurosci. 2023 Apr 26;43(17):3094-3106. doi: 10.1523/JNEUROSCI.1406-22.2023. Epub 2023 Mar 13.
PubMed 36914263Hackney AC, ed. Sex Hormones, Exercise and Women: Scientific and Clinical Aspects. 1st ed. 2017. Springer International Publishing : Imprint: Springer; 2017. doi:10.1007/978-3-319-44558-81
Gilli F, DiSano KD, Pachner AR. SeXX Matters in Multiple Sclerosis. Front Neurol. 2020 Jul 3;11:616. doi: 10.3389/fneur.2020.00616. eCollection 2020.
PubMed 32719651
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigating the Impact of Sex Hormones on Corticospinal Excitability, Motor Learning, and Fatigue in Females With Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT07081594
- Acronym / sponsor ID
- STU00224323
- Conditions
- Multiple Sclerosis
- Keywords
- Multiple Sclerosis, Sex hormones, menstrual cycle
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 14 participants (estimated)
- Lead sponsor
- Milap SandhuUniversity, hospital or other
- Study start
- 28 Aug 2025 (actual)
- Primary completion
- Mar 2027 (estimated)
- Study completion
- Mar 2029 (estimated)
- First posted
- 23 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pre-Menopausal Women | – | –Naturally cycling women with multiple sclerosis |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Persons with menstrual cycles and any form of multiple sclerosis
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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
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)
3 secondary outcomes
strength
Time frame: At 3 points during the individual's 1-month menstrual cycle, 1) Early Follicular 2) Late Follicular 3) Luteal
Fatigue
Time frame: At 3 points during the individual's 1-month menstrual cycle, 1) Early Follicular 2) Late Follicular 3) Luteal
Motor Learning
Time frame: At 3 points during the individual's 1-month menstrual cycle, 1) Early Follicular 2) Late Follicular 3) Luteal
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2026.
- Background: PubMed 35963205Christogianni A, O'Garro J, Bibb R, Filtness A, Filingeri D. Heat and cold sensitivity in multiple sclerosis: A patient-centred perspective on triggers, symptoms, and thermal resilience practices. Mult Scler Relat Disord. 2022 Nov;67:104075. doi: 10.1016/j.msard.2022.104075. Epub 2022 Jul 25.
- Background: PubMed 27845228Karim HT, Huppert TJ, Erickson KI, Wollam ME, Sparto PJ, Sejdic E, VanSwearingen JM. Motor sequence learning-induced neural efficiency in functional brain connectivity. Behav Brain Res. 2017 Feb 15;319:87-95. doi: 10.1016/j.bbr.2016.11.021. Epub 2016 Nov 11.
- Background: PubMed 36914263Casamento-Moran A, Mooney RA, Chib VS, Celnik PA. Cerebellar Excitability Regulates Physical Fatigue Perception. J Neurosci. 2023 Apr 26;43(17):3094-3106. doi: 10.1523/JNEUROSCI.1406-22.2023. Epub 2023 Mar 13.
- BackgroundHackney AC, ed. Sex Hormones, Exercise and Women: Scientific and Clinical Aspects. 1st ed. 2017. Springer International Publishing : Imprint: Springer; 2017. doi:10.1007/978-3-319-44558-81
- Background: PubMed 32719651Gilli F, DiSano KD, Pachner AR. SeXX Matters in Multiple Sclerosis. Front Neurol. 2020 Jul 3;11:616. doi: 10.3389/fneur.2020.00616. eCollection 2020.
- Individual participant dataSharing planned: Yes. De-Identified data will be available after completion of the study upon request
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Milap Sandhu, PT, PhD principal investigator
Shirley Ryan AbilityLab
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Multiple Sclerosis, run by Milap Sandhu at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 20 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Corticospinal excitability (time frame: At 3 points during the individual's 1-month menstrual cycle, 1) Early Follicular 2) Late Follicular 3) Luteal). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07081594, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2026.