HealthyNCT04471805
4 mA tDCS, Estrogen, and Leg Muscle Fatigability
A study testing Transcranial direct current stimulation 4 mA in people with Healthy, run by University of Iowa at 1 site in United States.
Trial summary
The majority of transcranial direct current stimulation (tDCS) studies have failed to consider sex as a modulating factor. This neglect may partly account for the high inter-subject variability bemoaned by many tDCS investigators (e.g., approximately 50% of participants do not respond to tDCS) and has certainly… Read more about this study
- Who is it for?
- Ages 18 to 35 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Transcranial direct current stimulation 4 mA
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2020to 1 Nov 2021
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 35 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Has a regular menstrual cycle
- Young adult (18-35 years)
- Right-side dominant
- At least 30 min of moderate-intensity, physical activity on at least 3 days of the week for at least the last 3 months
- Without chronic neurological, psychiatric, or medical conditions
- Not taking any psychoactive medications.
Who cannot join
- Pregnant
- Known holes or fissures in the skull
- Metallic objects or implanted devices in the skull (e.g., metal plate)
- Women on hormonal contraceptives/supplements.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Estrogen Levels and Leg Muscle Fatigability in Eumenorrheic Young Women After 4 mA Transcranial Direct Current Stimulation
The majority of transcranial direct current stimulation (tDCS) studies have failed to consider sex as a modulating factor. This neglect may partly account for the high inter-subject variability bemoaned by many tDCS investigators (e.g., approximately 50% of participants do not respond to tDCS) and has certainly delayed progress in the field. Therefore, research into how sex influences stimulation-related outcomes is vital to fully understand the underlying mechanisms of tDCS, which has shown great inconsistency.
Because of the menstrual cycle, the hormonal levels of women fluctuate considerably more than in men. Importantly, these hormonal variations might impact the efficacy of neuromodulatory tools, like tDCS. It is suggested that estrogen, which is high in the second follicular phase, reinforces excitatory mechanisms in the motor cortex. However, because anodal tDCS enhances cortical excitation there is also a possibility of excessive excitability. For instance, anodal tDCS may lead to overexcitation and non-optimal performance when it is applied in the second follicular phase of the menstrual cycle. Currently, there is a lack of knowledge on how the phases of the menstrual cycle affect tDCS performance outcomes in healthy young women because no studies have examined if and how the phases of the menstrual cycle alter tDCS efficacy.
This study is critical for determining the optimal time to administer anodal tDCS, and the ideal intensity for that administration, to achieve the most beneficial results. Furthermore, this investigation will emphasize the need for future tDCS studies to test women during the same menstrual cycle phase.
Read the detailed description
The majority of transcranial direct current stimulation (tDCS) studies have failed to consider sex as a modulating factor. This neglect may partly account for the high inter-subject variability bemoaned by many tDCS investigators (e.g., approximately 50% of participants do not respond to tDCS) and has certainly delayed progress in the field. Therefore, research into how sex influences stimulation-related outcomes is vital to fully understand the underlying mechanisms of tDCS, which has shown great inconsistency.
Because of the menstrual cycle, the hormonal levels of women fluctuate considerably more than in men. There are two main phases of the menstrual cycle: 1) the follicular phase, characterized by low levels of estradiol and progesterone (first follicular phase, days 1-7) followed by increased levels of estradiol and low levels of progesterone (second follicular phase, days 7-14); and 2) the luteal phase (days 14-28), characterized by moderate estradiol and high progesterone levels. Importantly, these hormonal variations might impact the efficacy of neuromodulatory tools, like tDCS.
It is suggested that estrogen, which is high in the second follicular phase, reinforces excitatory mechanisms in the motor cortex. Thus, it appears that higher levels of estradiol increase cortical excitability. However, because anodal tDCS enhances cortical excitation there is also a possibility of excessive excitability. For instance, anodal tDCS may lead to overexcitation and nonoptimal performance when it is applied in the second follicular phase of the menstrual cycle. Currently, there is a lack of knowledge on how the phases of the menstrual cycle affect tDCS performance outcomes in healthy young women because no studies have examined if and how the phases of the menstrual cycle alter tDCS efficacy.
This research will be significant because the changing hormone levels during the different phases of menstruation in women is an especially important factor for minimizing response variability from tDCS. Thus, this study is critical for determining the optimal time to administer anodal tDCS, and the ideal intensity for that administration, to achieve the most beneficial results. Furthermore, this investigation will emphasize the need for future tDCS studies to test women during the same menstrual cycle phase.
- Conditions
- Healthy
- Being tested
- Sham transcranial direct current stimulation 4 mA, Transcranial direct current stimulation 4 mA
- Keywords
- transcranial direct current stimulation, muscle fatigue, brain stimulation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sham transcranial direct current stimulation 4 mADevice
Also called Sham tDCS 2 mA
Uses weak electrical current (4 mA intensity) at the beginning and the end of a given stimulation period to control for potential placebo-like effects or participant expectation bias.
Transcranial direct current stimulation 4 mADevice
Also called tDCS 4 mA
Uses weak electrical current (4 mA intensity) to either increase or decrease brain excitability and improve functional or cognitive outcomes.
| Study group | Role | What they receive |
|---|---|---|
| Eumenorrheic Women | Experimental | Participants will have the anode (active electrode) placed over the brain area that controls their dominant leg and the cathode (return electrode) above the ipsilateral eyebrow. tDCS is administered in the early follicular phase, late follicular phase, and mid-luteal phase of their menstrual cycle.
tDCS: Stimulation is ramped up to 4 mA over the first 30 seconds and stays at 4 mA for the remainder of the simulation time.
Sham: Stimulation is turned on (4 mA) for 30 seconds at the beginning and the end of the trial but stays at 0 mA in the intervening time. Receives: Device: Sham transcranial direct current stimulation 4 mA; Device: Transcranial direct current stimulation 4 mA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fatigue Index From the Isokinetic Fatigue Test
Perform 40 consecutive flexion and extension repetitions of the knee on the dominant leg. After a 10 minute rest, do the same task on the non-dominant leg.
The fatigue index was calculated using the greatest torque from the relevant repetitions of the fatigue test as follows: ([mean of reps 3 through 7-mean of last five reps]/mean of reps 3 through 7) X 100 and is expressed as a percentage of decline in torque production.
Measured: Completed at each visit, spaced approximately 14 days apart for 2 consecutive months
Muscle Activity During the Strength and Fatigue Tests
Collect electromyographic (EMG; muscle activity) information during the fatigue tests. Muscle activity is measured as electrical signals/voltages.
The muscle activity of the knee extensors (rectus femoris, vastus medialis, and vastus lateralis) was averaged to represent the cumulative activity of this muscle group. The first two repetitions of the fatigue test were considered adaptation repetitions and were removed. Therefore, the remaining 38 repetitions were used for the average EMG analyses. The subsequent 38 repetitions were also organized into 8 windows. The first seven windows consisted of five consecutive and non-overlapping repetitions (e.g., window 2 = reps 8-12; window 3 = reps 13-17, etc.) while the last (eighth) window was comprised of the final three repetitions.
Measured: Completed at each visit, spaced approximately 14 days apart for 2 consecutive months
Secondary outcomes (1)
Estrogen Level
Staff nurses collected 4.5 mL of blood from the median cubital vein of the left arm (total volume collected per subject = 9 mL) for the estrogen assay. Samples were immediately analyzed for serum estrogen levels after the blood draws by University of Iowa Hospitals and Clinics Pathology technicians using an Electrochemiluminescence Assay (Roche Diagnostics, Basel, Switzerland). The estrogen assay had a lower limit of detection of 5 pg/mL and a coefficient of variation of 8%.
Because menstrual cycles have great inter- and intrasubject variability, the peak estrogen levels of the subjects were not consistently found in the late-follicular phase, which is a common failing of menstrual cycle phase calendar estimation. Thus, estrogen levels were grouped as high or low according to each individual subject's estrogen serum levels, irrespective of the anticipated/targeted phase.
Measured: Completed at each visit, spaced approximately 14 days apart for 2 consecutive months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jul 2020
- Study start1 Oct 2020
- Primary completion1 Nov 2021
- Study completion1 Nov 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by University of IowaThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Iowa
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Thorsten Rudroff, University of Iowa
- Investigators
- Thorsten Rudroff, PhD, Principal investigator, Health and Human Physiology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04471805
- Sponsor's protocol ID
- 202005124
- Status last verified
- Apr 2023
- First submitted
- 10 Jul 2020
- Last updated
- 10 May 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Estrogen Levels and Leg Muscle Fatigability in Eumenorrheic Young Women After 4 mA Transcranial Direct Current Stimulation
- ClinicalTrials.gov ID
- NCT04471805
- Acronym / sponsor ID
- 202005124
- Conditions
- Healthy
- Keywords
- transcranial direct current stimulation, muscle fatigue, brain stimulation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- University of IowaUniversity, hospital or other
- Study start
- 1 Oct 2020 (actual)
- Primary completion
- 1 Nov 2021 (actual)
- Study completion
- 1 Nov 2021 (actual)
- First posted
- 15 Jul 2020 (actual)
- Results
- Posted 10 May 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The majority of transcranial direct current stimulation (tDCS) studies have failed to consider sex as a modulating factor. This neglect may partly account for the high inter-subject variability bemoaned by many tDCS investigators (e.g., approximately 50% of participants do not respond to tDCS) and has certainly delayed progress in the field. Therefore, research into how sex influences stimulation-related outcomes is vital to fully understand the underlying mechanisms of tDCS, which has shown great inconsistency.
Because of the menstrual cycle, the hormonal levels of women fluctuate considerably more than in men. Importantly, these hormonal variations might impact the efficacy of neuromodulatory tools, like tDCS. It is suggested that estrogen, which is high in the second follicular phase, reinforces excitatory mechanisms in the motor cortex. However, because anodal tDCS enhances cortical excitation there is also a possibility of excessive excitability. For instance, anodal tDCS may lead to overexcitation and non-optimal performance when it is applied in the second follicular phase of the menstrual cycle. Currently, there is a lack of knowledge on how the phases of the menstrual cycle affect tDCS performance outcomes in healthy young women because no studies have examined if and how the phases of the menstrual cycle alter tDCS efficacy.
This study is critical for determining the optimal time to administer anodal tDCS, and the ideal intensity for that administration, to achieve the most beneficial results. Furthermore, this investigation will emphasize the need for future tDCS studies to test women during the same menstrual cycle phase.
Detailed description
The majority of transcranial direct current stimulation (tDCS) studies have failed to consider sex as a modulating factor. This neglect may partly account for the high inter-subject variability bemoaned by many tDCS investigators (e.g., approximately 50% of participants do not respond to tDCS) and has certainly delayed progress in the field. Therefore, research into how sex influences stimulation-related outcomes is vital to fully understand the underlying mechanisms of tDCS, which has shown great inconsistency.
Because of the menstrual cycle, the hormonal levels of women fluctuate considerably more than in men. There are two main phases of the menstrual cycle: 1) the follicular phase, characterized by low levels of estradiol and progesterone (first follicular phase, days 1-7) followed by increased levels of estradiol and low levels of progesterone (second follicular phase, days 7-14); and 2) the luteal phase (days 14-28), characterized by moderate estradiol and high progesterone levels. Importantly, these hormonal variations might impact the efficacy of neuromodulatory tools, like tDCS.
It is suggested that estrogen, which is high in the second follicular phase, reinforces excitatory mechanisms in the motor cortex. Thus, it appears that higher levels of estradiol increase cortical excitability. However, because anodal tDCS enhances cortical excitation there is also a possibility of excessive excitability. For instance, anodal tDCS may lead to overexcitation and nonoptimal performance when it is applied in the second follicular phase of the menstrual cycle. Currently, there is a lack of knowledge on how the phases of the menstrual cycle affect tDCS performance outcomes in healthy young women because no studies have examined if and how the phases of the menstrual cycle alter tDCS efficacy.
This research will be significant because the changing hormone levels during the different phases of menstruation in women is an especially important factor for minimizing response variability from tDCS. Thus, this study is critical for determining the optimal time to administer anodal tDCS, and the ideal intensity for that administration, to achieve the most beneficial results. Furthermore, this investigation will emphasize the need for future tDCS studies to test women during the same menstrual cycle phase.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Eumenorrheic Women | Experimental | Device: Sham transcranial direct current stimulation 4 mA, Device: Transcranial direct current stimulation 4 mAParticipants will have the anode (active electrode) placed over the brain area that controls their dominant leg and the cathode (return electrode) above the ipsilateral eyebrow. tDCS is administered in the early follicular phase, late follicular phase, and mid-luteal phase of their menstrual cycle. tDCS: Stimulation is ramped up to 4 mA over the first 30 seconds and stays at 4 mA for the remainder of the simulation time. Sham: Stimulation is turned on (4 mA) for 30 seconds at the beginning and the end of the trial but stays at 0 mA in the intervening time. |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Has a regular menstrual cycle
- Young adult (18-35 years)
- Right-side dominant
- At least 30 min of moderate-intensity, physical activity on at least 3 days of the week for at least the last 3 months
- Without chronic neurological, psychiatric, or medical conditions
Key exclusion criteria (4 listed)
- Pregnant
- Known holes or fissures in the skull
- Metallic objects or implanted devices in the skull (e.g., metal plate)
- Women on hormonal contraceptives/supplements.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sham transcranial direct current stimulation 4 mAAlso: Sham tDCS 2 mAUses weak electrical current (4 mA intensity) at the beginning and the end of a given stimulation period to control for potential placebo-like effects or participant expectation bias. | Device | Eumenorrheic Women |
| Transcranial direct current stimulation 4 mAAlso: tDCS 4 mAUses weak electrical current (4 mA intensity) to either increase or decrease brain excitability and improve functional or cognitive outcomes. | Device | Eumenorrheic Women |
Primary outcome
Fatigue Index From the Isokinetic Fatigue Test
Time frame: Completed at each visit, spaced approximately 14 days apart for 2 consecutive months
Perform 40 consecutive flexion and extension repetitions of the knee on the dominant leg. After a 10 minute rest, do the same task on the non-dominant leg. The fatigue index was calculated using the greatest torque from the relevant repetitions of the fatigue test as follows: ([mean of reps 3 through 7-mean of last five reps]/mean of reps 3 through 7) X 100 and is expressed as a percentage of decline in torque production.
Muscle Activity During the Strength and Fatigue Tests
Time frame: Completed at each visit, spaced approximately 14 days apart for 2 consecutive months
Collect electromyographic (EMG; muscle activity) information during the fatigue tests. Muscle activity is measured as electrical signals/voltages. The muscle activity of the knee extensors (rectus femoris, vastus medialis, and vastus lateralis) was averaged to represent the cumulative activity of this muscle group. The first two repetitions of the fatigue test were considered adaptation repetitions and were removed. Therefore, the remaining 38 repetitions were used for the average EMG analyses. The subsequent 38 repetitions were also organized into 8 windows. The first seven windows consisted of five consecutive and non-overlapping repetitions (e.g., window 2 = reps 8-12; window 3 = reps 13-17, etc.) while the last (eighth) window was comprised of the final three repetitions.
1 secondary outcome
Estrogen Level
Time frame: Completed at each visit, spaced approximately 14 days apart for 2 consecutive months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Thorsten Rudroff, PhD principal investigator
Health and Human Physiology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcranial direct current stimulation 4 mA in people with Healthy, run by University of Iowa 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 6 inclusion and 4 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: finished, as of the sponsor's last update on 10 May 2023. 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?
Yes. Results are posted in the registry (first posted 10 May 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Fatigue Index From the Isokinetic Fatigue Test (time frame: Completed at each visit, spaced approximately 14 days apart for 2 consecutive months). 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?
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 10 May 2023.