Clinical trial NCT04471805: 4 mA tDCS, Estrogen, and Leg Muscle Fatigability
Official title: Estrogen Levels and Leg Muscle Fatigability in Eumenorrheic Young Women After 4 mA Transcranial Direct Current Stimulation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy
Keywords: transcranial direct current stimulation
muscle fatigue
brain stimulation
Lead sponsor: University of Iowa
Sponsor class: OTHER
First posted: 2020-07-15
Enrollment: 10
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: Inclusion Criteria:

1. Has a regular menstrual cycle
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.

Primary outcomes:
measure: Fatigue Index From the Isokinetic Fatigue Test
timeFrame: Completed at each visit, spaced approximately 14 days apart for 2 consecutive months
measure: Muscle Activity During the Strength and Fatigue Tests
timeFrame: Completed at each visit, spaced approximately 14 days apart for 2 consecutive months
Secondary outcomes:
measure: Estrogen Level
timeFrame: Completed at each visit, spaced approximately 14 days apart for 2 consecutive months
Other outcomes:
Locations:
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
Study officials:
affiliation: Health and Human Physiology
name: Thorsten Rudroff, PhD
role: PRINCIPAL_INVESTIGATOR
References: