tDCS and Sex Differences

Sponsor
University of Iowa (Other)
Overall Status
Completed
CT.gov ID
NCT04471805
Collaborator
(none)
10
1
8
13
0.8

Study Details

Study Description

Brief 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 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.

Condition or Disease Intervention/Treatment Phase
  • Device: Sham transcranial direct current stimulation 2 mA
  • Device: Transcranial direct current stimulation 2 mA
  • Device: Sham transcranial direct current stimulation 4 mA
  • Device: Transcranial direct current stimulation 4 mA
N/A

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

Study Type:
Interventional
Actual Enrollment :
10 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
Sex Differences in Outcomes From Transcranial Direct Current Stimulation
Actual Study Start Date :
Oct 1, 2020
Actual Primary Completion Date :
Nov 1, 2021
Actual Study Completion Date :
Nov 1, 2021

Arms and Interventions

Arm Intervention/Treatment
Sham Comparator: Women Sham 2 mA

Participants will have the anode (active electrode) placed over the brain area the controls their dominant leg and the cathode (return electrode) above the ipsilateral eyebrow. Stimulation is turned on (2 mA) for the 30 seconds at the beginning and the end of the trial but stays at 0 mA in the intervening time.

Device: Sham transcranial direct current stimulation 2 mA
Uses weak electrical current (2 mA intensity) at the beginning and the end of a given stimulation period to control for potential placebo-like effects or participant expectation bias.
Other Names:
  • Sham tDCS 2 mA
  • Experimental: Women tDCS 2 mA

    Participants will have the anode (active electrode) placed over the brain area the controls their dominant leg and the cathode (return electrode) above the ipsilateral eyebrow. Stimulation is ramped up to 2 mA over the first 30 seconds and stays at 2 mA for the remainder of the stimulation time.

    Device: Transcranial direct current stimulation 2 mA
    Uses weak electrical current (2 mA intensity) to either increase or decrease brain excitability and improve functional or cognitive outcomes.
    Other Names:
  • tDCS 2 mA
  • Sham Comparator: Women Sham 4 mA

    Participants will have the anode (active electrode) placed over the brain area the controls their dominant leg and the cathode (return electrode) above the ipsilateral eyebrow. Stimulation is turned on (4 mA) for the 30 seconds at the beginning and the end of the trial but stays at 0 mA in the intervening time.

    Device: Sham transcranial direct current stimulation 4 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.
    Other Names:
  • Sham tDCS 2 mA
  • Experimental: Women tDCS 4 mA

    Participants will have the anode (active electrode) placed over the brain area the controls their dominant leg and the cathode (return electrode) above the ipsilateral eyebrow. Stimulation is ramped up to 4 mA over the first 30 seconds and stays at 4 mA for the remainder of the stimulation time.

    Device: Transcranial direct current stimulation 4 mA
    Uses weak electrical current (4 mA intensity) to either increase or decrease brain excitability and improve functional or cognitive outcomes.
    Other Names:
  • tDCS 4 mA
  • Sham Comparator: Men Sham 2 mA

    Participants will have the anode (active electrode) placed over the brain area the controls their dominant leg and the cathode (return electrode) above the ipsilateral eyebrow. Stimulation is turned on (2 mA) for the 30 seconds at the beginning and the end of the trial but stays at 0 mA in the intervening time.

    Device: Sham transcranial direct current stimulation 2 mA
    Uses weak electrical current (2 mA intensity) at the beginning and the end of a given stimulation period to control for potential placebo-like effects or participant expectation bias.
    Other Names:
  • Sham tDCS 2 mA
  • Experimental: Men tDCS 2 mA

    Participants will have the anode (active electrode) placed over the brain area the controls their dominant leg and the cathode (return electrode) above the ipsilateral eyebrow. Stimulation is ramped up to 2 mA over the first 30 seconds and stays at 2 mA for the remainder of the stimulation time.

    Device: Transcranial direct current stimulation 2 mA
    Uses weak electrical current (2 mA intensity) to either increase or decrease brain excitability and improve functional or cognitive outcomes.
    Other Names:
  • tDCS 2 mA
  • Sham Comparator: Men Sham 4 mA

    Participants will have the anode (active electrode) placed over the brain area the controls their dominant leg and the cathode (return electrode) above the ipsilateral eyebrow. Stimulation is turned on (4 mA) for the 30 seconds at the beginning and the end of the trial but stays at 0 mA in the intervening time.

    Device: Sham transcranial direct current stimulation 4 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.
    Other Names:
  • Sham tDCS 2 mA
  • Experimental: Men tDCS 4 mA

    Participants will have the anode (active electrode) placed over the brain area the controls their dominant leg and the cathode (return electrode) above the ipsilateral eyebrow. Stimulation is ramped up to 4 mA over the first 30 seconds and stays at 4 mA for the remainder of the stimulation time.

    Device: Transcranial direct current stimulation 4 mA
    Uses weak electrical current (4 mA intensity) to either increase or decrease brain excitability and improve functional or cognitive outcomes.
    Other Names:
  • tDCS 4 mA
  • Outcome Measures

    Primary Outcome Measures

    1. Maximal Isometric Leg Strength [Through study completion, up to 6 months]

      Straighten the knee as hard as possible against a fixed-position resistance and measure the force (effort) of the movement.

    2. Maximal Isokinetic Leg Strength [Through study completion, up to 6 months]

      Straighten the knee as hard as possible against a fixed-speed resistance and measures the force (effort) of the movement.

    3. Fatigue index from the isokinetic fatigue test [Through study completion, up to 6 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.

    4. Muscle activity during the strength and fatigue tests [Through study completion, up to 6 months]

      Collect electromyographic (EMG; muscle activity) information during all of the strength and fatigue tests.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 35 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:
    1. Has a regular menstrual cycle (for women only)

    2. Young adult (18-35 years)

    3. Right-side dominant

    4. At least 30 min of moderate-intensity, physical activity on at least 3 days of the week for at least the last 3 months

    5. Without chronic neurological, psychiatric, or medical conditions

    6. Not taking any psychoactive medications.

    Exclusion Criteria:
    1. Pregnant

    2. Known holes or fissures in the skull

    3. Metallic objects or implanted devices in the skull (e.g., metal plate)

    4. Women on hormonal contraceptives/supplements.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Iowa Iowa City Iowa United States 52242

    Sponsors and Collaborators

    • University of Iowa

    Investigators

    • Principal Investigator: Thorsten Rudroff, PhD, Health and Human Physiology

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Thorsten Rudroff, Assistant Professor, University of Iowa
    ClinicalTrials.gov Identifier:
    NCT04471805
    Other Study ID Numbers:
    • 202005124
    First Posted:
    Jul 15, 2020
    Last Update Posted:
    May 24, 2022
    Last Verified:
    May 1, 2022
    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.:
    No
    Keywords provided by Thorsten Rudroff, Assistant Professor, University of Iowa

    Study Results

    No Results Posted as of May 24, 2022