Trial Outcomes & Findings for 4 mA tDCS, Estrogen, and Leg Muscle Fatigability (NCT NCT04471805)

Last Updated: 2023-05-10

Results Overview

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.

Recruitment status

COMPLETED

Study phase

Target enrollment

10 participants

Primary outcome timeframe

Completed at each visit, spaced approximately 14 days apart for 2 consecutive months

Results posted on

2023-05-10

Participant Flow

Participant milestones

Participant milestones
Measure	Eumenorrheic Women 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.
Overall Study STARTED	10
Overall Study tDCS, Early Follicular Phase	10
Overall Study Sham, Early Follicular Phase	10
Overall Study tDCS, Late Follicular Phase	10
Overall Study Sham, Late Follicular Phase	10
Overall Study tDCS, Mid-Luteal Phase	10
Overall Study Sham, Mid-Luteal Phase	10
Overall Study COMPLETED	10
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

4 mA tDCS, Estrogen, and Leg Muscle Fatigability

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Eumenorrheic Women n=10 Participants Biological women will have the anode (active electrode) placed over the brain area the controls their dominant leg and the cathode (return electrode) above the eyebrow on the opposite side of the head. 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. Stimulation is ramped up to 2 mA over the first 30 seconds and stays at 2 mA for the remainder of the stimulation time. Sham transcranial direct current stimulation 2 mA/4mA: Uses weak electrical current (2 mA or 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. Stimulation is turned on (2 mA or 4 mA) for the 30 seconds at the beginning and the end of the trial but stays at 0 mA in the intervening time.
Age, Continuous	24.3 years STANDARD_DEVIATION 5.5 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	10 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	10 participants n=5 Participants

PRIMARY outcome

Timeframe: Completed at each visit, spaced approximately 14 days apart for 2 consecutive months

Outcome measures

Outcome measures
Measure	Eumenorrheic Women n=10 Participants 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.
Fatigue Index From the Isokinetic Fatigue Test tDCS High Estrogen	61.7 Percent decline Standard Deviation 10.6
Fatigue Index From the Isokinetic Fatigue Test Sham High Estrogen	46.7 Percent decline Standard Deviation 20.0
Fatigue Index From the Isokinetic Fatigue Test tDCS Low Estrogen	57.28 Percent decline Standard Deviation 11.57
Fatigue Index From the Isokinetic Fatigue Test Sham Low Estrogen	55.90 Percent decline Standard Deviation 8.67

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Eumenorrheic Women n=10 Participants 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.
Muscle Activity During the Strength and Fatigue Tests tDCS High Estrogen	95.15 Microvolts Standard Deviation 26.46
Muscle Activity During the Strength and Fatigue Tests tDCS Low Estrogen	91.83 Microvolts Standard Deviation 16.48
Muscle Activity During the Strength and Fatigue Tests Sham High Estrogen	77.53 Microvolts Standard Deviation 19.71
Muscle Activity During the Strength and Fatigue Tests Sham Low Estrogen	82.35 Microvolts Standard Deviation 21.44

SECONDARY outcome

Timeframe: Completed at each visit, spaced approximately 14 days apart for 2 consecutive months

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.

Outcome measures

Outcome measures
Measure	Eumenorrheic Women n=10 Participants 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.
Estrogen Level tDCS High Estrogen	157.7 (pg/mL) Standard Deviation 101.5
Estrogen Level tDCS Low Estrogen	31.9 (pg/mL) Standard Deviation 10.9
Estrogen Level Sham Low Estrogen	42.9 (pg/mL) Standard Deviation 25.1
Estrogen Level Sham High Estrogen	137.2 (pg/mL) Standard Deviation 114.0

Adverse Events

Eumenorrheic Women

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Thorsten Rudroff, PhD

University of Iowa, Department of Health and Human Physiology

Phone: (319)467-0363

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place