Trial Outcomes & Findings for Effects of a Combined Transcranial Magnetic Stimulation (TMS) and Cognitive Training in Alzheimer Patients (NCT NCT01504958)

Last Updated: 2017-07-02

Results Overview

Assessment to measure the severity of all of the most important symptoms of Alzheimer's disease: loss of memory, language, praxis, and attention. The total scoring range is 0-70, with 0 representing the least impairment and 70 the most severe impairment. The results posted below represent a change in score from baseline. A positive change represents an improvement on the ADAS-Cog (change = 1 month score - baseline score).

Recruitment status

COMPLETED

Study phase

Target enrollment

22 participants

Primary outcome timeframe

Pre treatment; 1 month post treatment

Results posted on

2017-07-02

Participant Flow

Participant milestones

Participant milestones
Measure	Active rTMS With Real Cognitive Training High frequency rTMS stimulation to the left and right parietal cortex (somatosensory association cortex), left and right DLPFC (dorsolateral prefrontal cortex), and left superior temporal gyrus (Broca's area). Repetitive Transcranial Magnetic Stimulation (rTMS): Each subject will receive up to 1800 pulses of up to 20Hz per day to all simulated brain regions together. Treated brain areas will be alternated each day (only 3 a day). Sham participants will receive the same study procedures as patients receiving active rTMS. NICE Cognitive Training: 12 levels of difficulty in tasks designed to relate to the region of the brain being stimulated (left and right parietal cortex, left and right DLPFC, left superior temporal gyrus, left inferior frontal gyrus). A particular cognitive exercise will start 200msec after the termination of each TMS train. Sham participants receive real cognitive training that follows the same procedures as the active group.	Sham rTMS With Real Cognitive Training High frequency sham rTMS to the left and right parietal cortex (somatosensory association cortex), left and right DLPFC (dorsolateral prefrontal cortex), and left superior temporal gyrus (Broca's area). Repetitive Transcranial Magnetic Stimulation (rTMS): Each subject will receive up to 1800 pulses of up to 20Hz per day to all simulated brain regions together. Treated brain areas will be alternated each day (only 3 a day). Sham participants will receive the same study procedures as patients receiving active rTMS. NICE Cognitive Training: 12 levels of difficulty in tasks designed to relate to the region of the brain being stimulated (left and right parietal cortex, left and right DLPFC, left superior temporal gyrus, left inferior frontal gyrus). A particular cognitive exercise will start 200msec after the termination of each TMS train. Sham participants receive real cognitive training that follows the same procedures as the active group.	Sham rTMS With Sham Cognitive Training High frequency sham rTMS stimulation to the left and right parietal cortex (somatosensory association cortex), left and right DLPFC (dorsolateral prefrontal cortex), and left superior temporal gyrus (Broca's area). Repetitive Transcranial Magnetic Stimulation (rTMS): Each subject will receive up to 1800 pulses of up to 20Hz per day to all simulated brain regions together. Treated brain areas will be alternated each day (only 3 a day). Sham participants will receive the same study procedures as patients receiving active rTMS. Sham Cognitive Training: subjects will undergo pseudo cognitive training with the sham rTMS following the same procedures as the active group
Overall Study STARTED	10	6	6
Overall Study COMPLETED	10	6	6
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Effects of a Combined Transcranial Magnetic Stimulation (TMS) and Cognitive Training in Alzheimer Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Active rTMS With Real Cognitive Training n=10 Participants High frequency rTMS stimulation to the left and right parietal cortex (somatosensory association cortex), left and right DLPFC (dorsolateral prefrontal cortex), and left superior temporal gyrus (Broca's area). Repetitive Transcranial Magnetic Stimulation (rTMS): Each subject will receive up to 1800 pulses of up to 20Hz per day to all simulated brain regions together. Treated brain areas will be alternated each day (only 3 a day). Sham participants will receive the same study procedures as patients receiving active rTMS. NICE Cognitive Training: 12 levels of difficulty in tasks designed to relate to the region of the brain being stimulated (left and right parietal cortex, left and right DLPFC, left superior temporal gyrus, left inferior frontal gyrus). A particular cognitive exercise will start 200msec after the termination of each TMS train. Sham participants receive real cognitive training that follows the same procedures as the active group.	Sham rTMS With Real Cognitive Training n=5 Participants High frequency sham rTMS to the left and right parietal cortex (somatosensory association cortex), left and right DLPFC (dorsolateral prefrontal cortex), and left superior temporal gyrus (Broca's area). Repetitive Transcranial Magnetic Stimulation (rTMS): Each subject will receive up to 1800 pulses of up to 20Hz per day to all simulated brain regions together. Treated brain areas will be alternated each day (only 3 a day). Sham participants will receive the same study procedures as patients receiving active rTMS. NICE Cognitive Training: 12 levels of difficulty in tasks designed to relate to the region of the brain being stimulated (left and right parietal cortex, left and right DLPFC, left superior temporal gyrus, left inferior frontal gyrus). A particular cognitive exercise will start 200msec after the termination of each TMS train. Sham participants receive real cognitive training that follows the same procedures as the active group.	Sham rTMS With Sham Cognitive Training n=6 Participants High frequency sham rTMS stimulation to the left and right parietal cortex (somatosensory association cortex), left and right DLPFC (dorsolateral prefrontal cortex), and left superior temporal gyrus (Broca's area). Repetitive Transcranial Magnetic Stimulation (rTMS): Each subject will receive up to 1800 pulses of up to 20Hz per day to all simulated brain regions together. Treated brain areas will be alternated each day (only 3 a day). Sham participants will receive the same study procedures as patients receiving active rTMS. Sham Cognitive Training: subjects will undergo pseudo cognitive training with the sham rTMS following the same procedures as the active group	Total n=21 Participants Total of all reporting groups
Age, Continuous	69.1 years n=5 Participants	68.6 years n=7 Participants	70 years n=5 Participants	69.24 years n=4 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	12 Participants n=4 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants	9 Participants n=4 Participants

PRIMARY outcome

Timeframe: Pre treatment; 1 month post treatment

Outcome measures

Outcome measures
Measure	Active rTMS With Real Cognitive Training n=10 Participants High frequency rTMS stimulation to the left and right parietal cortex (somatosensory association cortex), left and right DLPFC (dorsolateral prefrontal cortex), and left superior temporal gyrus (Broca's area). Repetitive Transcranial Magnetic Stimulation (rTMS): Each subject will receive up to 1800 pulses of up to 20Hz per day to all simulated brain regions together. Treated brain areas will be alternated each day (only 3 a day). Sham participants will receive the same study procedures as patients receiving active rTMS. NICE Cognitive Training: 12 levels of difficulty in tasks designed to relate to the region of the brain being stimulated (left and right parietal cortex, left and right DLPFC, left superior temporal gyrus, left inferior frontal gyrus). A particular cognitive exercise will start 200msec after the termination of each TMS train. Sham participants receive real cognitive training that follows the same procedures as the active group.	Sham rTMS With Real Cognitive Training n=5 Participants High frequency sham rTMS to the left and right parietal cortex (somatosensory association cortex), left and right DLPFC (dorsolateral prefrontal cortex), and left superior temporal gyrus (Broca's area). Repetitive Transcranial Magnetic Stimulation (rTMS): Each subject will receive up to 1800 pulses of up to 20Hz per day to all simulated brain regions together. Treated brain areas will be alternated each day (only 3 a day). Sham participants will receive the same study procedures as patients receiving active rTMS. NICE Cognitive Training: 12 levels of difficulty in tasks designed to relate to the region of the brain being stimulated (left and right parietal cortex, left and right DLPFC, left superior temporal gyrus, left inferior frontal gyrus). A particular cognitive exercise will start 200msec after the termination of each TMS train. Sham participants receive real cognitive training that follows the same procedures as the active group.	Sham rTMS With Sham Cognitive Training n=6 Participants High frequency sham rTMS stimulation to the left and right parietal cortex (somatosensory association cortex), left and right DLPFC (dorsolateral prefrontal cortex), and left superior temporal gyrus (Broca's area). Repetitive Transcranial Magnetic Stimulation (rTMS): Each subject will receive up to 1800 pulses of up to 20Hz per day to all simulated brain regions together. Treated brain areas will be alternated each day (only 3 a day). Sham participants will receive the same study procedures as patients receiving active rTMS. Sham Cognitive Training: subjects will undergo pseudo cognitive training with the sham rTMS following the same procedures as the active group
Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog)	1.79 percentage change Standard Deviation 3.60	-0.20 percentage change Standard Deviation 5.45	-0.66 percentage change Standard Deviation 2.91

SECONDARY outcome

Timeframe: Pre-treatment, 1 month post treatment

The CGI is a three-item scale used to assess treatment response in psychiatric patients. The CGI-C subset measures the global improvement or change from baseline. Scores range from 0 to 7, with 0 indicating marked improvement and 7 indicating marked worsening. The scores below represent the percent change of the scores from baseline.

Outcome measures

Outcome measures
Measure	Active rTMS With Real Cognitive Training n=10 Participants High frequency rTMS stimulation to the left and right parietal cortex (somatosensory association cortex), left and right DLPFC (dorsolateral prefrontal cortex), and left superior temporal gyrus (Broca's area). Repetitive Transcranial Magnetic Stimulation (rTMS): Each subject will receive up to 1800 pulses of up to 20Hz per day to all simulated brain regions together. Treated brain areas will be alternated each day (only 3 a day). Sham participants will receive the same study procedures as patients receiving active rTMS. NICE Cognitive Training: 12 levels of difficulty in tasks designed to relate to the region of the brain being stimulated (left and right parietal cortex, left and right DLPFC, left superior temporal gyrus, left inferior frontal gyrus). A particular cognitive exercise will start 200msec after the termination of each TMS train. Sham participants receive real cognitive training that follows the same procedures as the active group.	Sham rTMS With Real Cognitive Training n=5 Participants High frequency sham rTMS to the left and right parietal cortex (somatosensory association cortex), left and right DLPFC (dorsolateral prefrontal cortex), and left superior temporal gyrus (Broca's area). Repetitive Transcranial Magnetic Stimulation (rTMS): Each subject will receive up to 1800 pulses of up to 20Hz per day to all simulated brain regions together. Treated brain areas will be alternated each day (only 3 a day). Sham participants will receive the same study procedures as patients receiving active rTMS. NICE Cognitive Training: 12 levels of difficulty in tasks designed to relate to the region of the brain being stimulated (left and right parietal cortex, left and right DLPFC, left superior temporal gyrus, left inferior frontal gyrus). A particular cognitive exercise will start 200msec after the termination of each TMS train. Sham participants receive real cognitive training that follows the same procedures as the active group.	Sham rTMS With Sham Cognitive Training n=6 Participants High frequency sham rTMS stimulation to the left and right parietal cortex (somatosensory association cortex), left and right DLPFC (dorsolateral prefrontal cortex), and left superior temporal gyrus (Broca's area). Repetitive Transcranial Magnetic Stimulation (rTMS): Each subject will receive up to 1800 pulses of up to 20Hz per day to all simulated brain regions together. Treated brain areas will be alternated each day (only 3 a day). Sham participants will receive the same study procedures as patients receiving active rTMS. Sham Cognitive Training: subjects will undergo pseudo cognitive training with the sham rTMS following the same procedures as the active group
Clinical Global Impression of Change (CGIC)	3.25 percent change Standard Deviation 0.72	4.40 percent change Standard Deviation 0.89	4.08 percent change Standard Deviation 1.02

SECONDARY outcome

Timeframe: Pre-treatment, 1 month Post-treatment

23 item scale to assess activities of daily living. Scores range from 0 to 78 with a higher score indicating less functional impairment. The scores reported below are the means of the actual scores from the assessments representing the percent change from baseline.

Outcome measures

Outcome measures
Measure	Active rTMS With Real Cognitive Training n=10 Participants High frequency rTMS stimulation to the left and right parietal cortex (somatosensory association cortex), left and right DLPFC (dorsolateral prefrontal cortex), and left superior temporal gyrus (Broca's area). Repetitive Transcranial Magnetic Stimulation (rTMS): Each subject will receive up to 1800 pulses of up to 20Hz per day to all simulated brain regions together. Treated brain areas will be alternated each day (only 3 a day). Sham participants will receive the same study procedures as patients receiving active rTMS. NICE Cognitive Training: 12 levels of difficulty in tasks designed to relate to the region of the brain being stimulated (left and right parietal cortex, left and right DLPFC, left superior temporal gyrus, left inferior frontal gyrus). A particular cognitive exercise will start 200msec after the termination of each TMS train. Sham participants receive real cognitive training that follows the same procedures as the active group.	Sham rTMS With Real Cognitive Training n=5 Participants High frequency sham rTMS to the left and right parietal cortex (somatosensory association cortex), left and right DLPFC (dorsolateral prefrontal cortex), and left superior temporal gyrus (Broca's area). Repetitive Transcranial Magnetic Stimulation (rTMS): Each subject will receive up to 1800 pulses of up to 20Hz per day to all simulated brain regions together. Treated brain areas will be alternated each day (only 3 a day). Sham participants will receive the same study procedures as patients receiving active rTMS. NICE Cognitive Training: 12 levels of difficulty in tasks designed to relate to the region of the brain being stimulated (left and right parietal cortex, left and right DLPFC, left superior temporal gyrus, left inferior frontal gyrus). A particular cognitive exercise will start 200msec after the termination of each TMS train. Sham participants receive real cognitive training that follows the same procedures as the active group.	Sham rTMS With Sham Cognitive Training n=6 Participants High frequency sham rTMS stimulation to the left and right parietal cortex (somatosensory association cortex), left and right DLPFC (dorsolateral prefrontal cortex), and left superior temporal gyrus (Broca's area). Repetitive Transcranial Magnetic Stimulation (rTMS): Each subject will receive up to 1800 pulses of up to 20Hz per day to all simulated brain regions together. Treated brain areas will be alternated each day (only 3 a day). Sham participants will receive the same study procedures as patients receiving active rTMS. Sham Cognitive Training: subjects will undergo pseudo cognitive training with the sham rTMS following the same procedures as the active group
Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL) Pre-Treatment	72.67 percent change Standard Deviation 5.07	73.60 percent change Standard Deviation 3.36	65.75 percent change Standard Deviation 6.80
Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL) Post-Treatment	69.78 percent change Standard Deviation 7.80	71.20 percent change Standard Deviation 5.93	61.75 percent change Standard Deviation 9.50

Adverse Events

Active rTMS With Real Cognitive Training

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Sham rTMS With Real Cognitive Training

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Sham rTMS With Sham Cognitive Training

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Active rTMS With Real Cognitive Training n=10 participants at risk High frequency rTMS stimulation to the left and right parietal cortex (somatosensory association cortex), left and right DLPFC (dorsolateral prefrontal cortex), and left superior temporal gyrus (Broca's area). Repetitive Transcranial Magnetic Stimulation (rTMS): Each subject will receive up to 1800 pulses of up to 20Hz per day to all simulated brain regions together. Treated brain areas will be alternated each day (only 3 a day). Sham participants will receive the same study procedures as patients receiving active rTMS. NICE Cognitive Training: 12 levels of difficulty in tasks designed to relate to the region of the brain being stimulated (left and right parietal cortex, left and right DLPFC, left superior temporal gyrus, left inferior frontal gyrus). A particular cognitive exercise will start 200msec after the termination of each TMS train. Sham participants receive real cognitive training that follows the same procedures as the active group.	Sham rTMS With Real Cognitive Training n=6 participants at risk High frequency sham rTMS to the left and right parietal cortex (somatosensory association cortex), left and right DLPFC (dorsolateral prefrontal cortex), and left superior temporal gyrus (Broca's area). Repetitive Transcranial Magnetic Stimulation (rTMS): Each subject will receive up to 1800 pulses of up to 20Hz per day to all simulated brain regions together. Treated brain areas will be alternated each day (only 3 a day). Sham participants will receive the same study procedures as patients receiving active rTMS. NICE Cognitive Training: 12 levels of difficulty in tasks designed to relate to the region of the brain being stimulated (left and right parietal cortex, left and right DLPFC, left superior temporal gyrus, left inferior frontal gyrus). A particular cognitive exercise will start 200msec after the termination of each TMS train. Sham participants receive real cognitive training that follows the same procedures as the active group.	Sham rTMS With Sham Cognitive Training n=6 participants at risk High frequency sham rTMS stimulation to the left and right parietal cortex (somatosensory association cortex), left and right DLPFC (dorsolateral prefrontal cortex), and left superior temporal gyrus (Broca's area). Repetitive Transcranial Magnetic Stimulation (rTMS): Each subject will receive up to 1800 pulses of up to 20Hz per day to all simulated brain regions together. Treated brain areas will be alternated each day (only 3 a day). Sham participants will receive the same study procedures as patients receiving active rTMS. Sham Cognitive Training: subjects will undergo pseudo cognitive training with the sham rTMS following the same procedures as the active group
Injury, poisoning and procedural complications Rib Fracture	0.00% 0/10 • Adverse events were collected from baseline to 1 month post-treatment All adverse events were self-reported according to a Side Effects Questionnaire administered at each visit.	0.00% 0/6 • Adverse events were collected from baseline to 1 month post-treatment All adverse events were self-reported according to a Side Effects Questionnaire administered at each visit.	16.7% 1/6 • Number of events 1 • Adverse events were collected from baseline to 1 month post-treatment All adverse events were self-reported according to a Side Effects Questionnaire administered at each visit.

Other adverse events

Additional Information

Alvaro Pascual-Leone, M.D., Ph.D.

Beth Israel Deaconess Medical Center

Phone: 617-667-0203

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Active rTMS With Real Cognitive Training n=10 participants at risk High frequency rTMS stimulation to the left and right parietal cortex (somatosensory association cortex), left and right DLPFC (dorsolateral prefrontal cortex), and left superior temporal gyrus (Broca's area). Repetitive Transcranial Magnetic Stimulation (rTMS): Each subject will receive up to 1800 pulses of up to 20Hz per day to all simulated brain regions together. Treated brain areas will be alternated each day (only 3 a day). Sham participants will receive the same study procedures as patients receiving active rTMS. NICE Cognitive Training: 12 levels of difficulty in tasks designed to relate to the region of the brain being stimulated (left and right parietal cortex, left and right DLPFC, left superior temporal gyrus, left inferior frontal gyrus). A particular cognitive exercise will start 200msec after the termination of each TMS train. Sham participants receive real cognitive training that follows the same procedures as the active group.	Sham rTMS With Real Cognitive Training n=6 participants at risk High frequency sham rTMS to the left and right parietal cortex (somatosensory association cortex), left and right DLPFC (dorsolateral prefrontal cortex), and left superior temporal gyrus (Broca's area). Repetitive Transcranial Magnetic Stimulation (rTMS): Each subject will receive up to 1800 pulses of up to 20Hz per day to all simulated brain regions together. Treated brain areas will be alternated each day (only 3 a day). Sham participants will receive the same study procedures as patients receiving active rTMS. NICE Cognitive Training: 12 levels of difficulty in tasks designed to relate to the region of the brain being stimulated (left and right parietal cortex, left and right DLPFC, left superior temporal gyrus, left inferior frontal gyrus). A particular cognitive exercise will start 200msec after the termination of each TMS train. Sham participants receive real cognitive training that follows the same procedures as the active group.	Sham rTMS With Sham Cognitive Training n=6 participants at risk High frequency sham rTMS stimulation to the left and right parietal cortex (somatosensory association cortex), left and right DLPFC (dorsolateral prefrontal cortex), and left superior temporal gyrus (Broca's area). Repetitive Transcranial Magnetic Stimulation (rTMS): Each subject will receive up to 1800 pulses of up to 20Hz per day to all simulated brain regions together. Treated brain areas will be alternated each day (only 3 a day). Sham participants will receive the same study procedures as patients receiving active rTMS. Sham Cognitive Training: subjects will undergo pseudo cognitive training with the sham rTMS following the same procedures as the active group
Musculoskeletal and connective tissue disorders Muscle Twitching	0.00% 0/10 • Adverse events were collected from baseline to 1 month post-treatment All adverse events were self-reported according to a Side Effects Questionnaire administered at each visit.	16.7% 1/6 • Adverse events were collected from baseline to 1 month post-treatment All adverse events were self-reported according to a Side Effects Questionnaire administered at each visit.	0.00% 0/6 • Adverse events were collected from baseline to 1 month post-treatment All adverse events were self-reported according to a Side Effects Questionnaire administered at each visit.
Nervous system disorders Headache	50.0% 5/10 • Adverse events were collected from baseline to 1 month post-treatment All adverse events were self-reported according to a Side Effects Questionnaire administered at each visit.	83.3% 5/6 • Adverse events were collected from baseline to 1 month post-treatment All adverse events were self-reported according to a Side Effects Questionnaire administered at each visit.	0.00% 0/6 • Adverse events were collected from baseline to 1 month post-treatment All adverse events were self-reported according to a Side Effects Questionnaire administered at each visit.
Musculoskeletal and connective tissue disorders Neck Pain	30.0% 3/10 • Adverse events were collected from baseline to 1 month post-treatment All adverse events were self-reported according to a Side Effects Questionnaire administered at each visit.	33.3% 2/6 • Adverse events were collected from baseline to 1 month post-treatment All adverse events were self-reported according to a Side Effects Questionnaire administered at each visit.	0.00% 0/6 • Adverse events were collected from baseline to 1 month post-treatment All adverse events were self-reported according to a Side Effects Questionnaire administered at each visit.
Musculoskeletal and connective tissue disorders Scalp Pain	30.0% 3/10 • Adverse events were collected from baseline to 1 month post-treatment All adverse events were self-reported according to a Side Effects Questionnaire administered at each visit.	0.00% 0/6 • Adverse events were collected from baseline to 1 month post-treatment All adverse events were self-reported according to a Side Effects Questionnaire administered at each visit.	0.00% 0/6 • Adverse events were collected from baseline to 1 month post-treatment All adverse events were self-reported according to a Side Effects Questionnaire administered at each visit.
Ear and labyrinth disorders Hearing Impairment	10.0% 1/10 • Adverse events were collected from baseline to 1 month post-treatment All adverse events were self-reported according to a Side Effects Questionnaire administered at each visit.	16.7% 1/6 • Adverse events were collected from baseline to 1 month post-treatment All adverse events were self-reported according to a Side Effects Questionnaire administered at each visit.	0.00% 0/6 • Adverse events were collected from baseline to 1 month post-treatment All adverse events were self-reported according to a Side Effects Questionnaire administered at each visit.
Nervous system disorders Impaired Cognition	0.00% 0/10 • Adverse events were collected from baseline to 1 month post-treatment All adverse events were self-reported according to a Side Effects Questionnaire administered at each visit.	16.7% 1/6 • Adverse events were collected from baseline to 1 month post-treatment All adverse events were self-reported according to a Side Effects Questionnaire administered at each visit.	0.00% 0/6 • Adverse events were collected from baseline to 1 month post-treatment All adverse events were self-reported according to a Side Effects Questionnaire administered at each visit.
Nervous system disorders Trouble Concentrating	0.00% 0/10 • Adverse events were collected from baseline to 1 month post-treatment All adverse events were self-reported according to a Side Effects Questionnaire administered at each visit.	66.7% 4/6 • Adverse events were collected from baseline to 1 month post-treatment All adverse events were self-reported according to a Side Effects Questionnaire administered at each visit.	0.00% 0/6 • Adverse events were collected from baseline to 1 month post-treatment All adverse events were self-reported according to a Side Effects Questionnaire administered at each visit.
Nervous system disorders Tiredness	30.0% 3/10 • Adverse events were collected from baseline to 1 month post-treatment All adverse events were self-reported according to a Side Effects Questionnaire administered at each visit.	16.7% 1/6 • Adverse events were collected from baseline to 1 month post-treatment All adverse events were self-reported according to a Side Effects Questionnaire administered at each visit.	0.00% 0/6 • Adverse events were collected from baseline to 1 month post-treatment All adverse events were self-reported according to a Side Effects Questionnaire administered at each visit.
Musculoskeletal and connective tissue disorders Soreness	10.0% 1/10 • Adverse events were collected from baseline to 1 month post-treatment All adverse events were self-reported according to a Side Effects Questionnaire administered at each visit.	0.00% 0/6 • Adverse events were collected from baseline to 1 month post-treatment All adverse events were self-reported according to a Side Effects Questionnaire administered at each visit.	0.00% 0/6 • Adverse events were collected from baseline to 1 month post-treatment All adverse events were self-reported according to a Side Effects Questionnaire administered at each visit.
Eye disorders Blurry Vision	10.0% 1/10 • Adverse events were collected from baseline to 1 month post-treatment All adverse events were self-reported according to a Side Effects Questionnaire administered at each visit.	0.00% 0/6 • Adverse events were collected from baseline to 1 month post-treatment All adverse events were self-reported according to a Side Effects Questionnaire administered at each visit.	0.00% 0/6 • Adverse events were collected from baseline to 1 month post-treatment All adverse events were self-reported according to a Side Effects Questionnaire administered at each visit.
Psychiatric disorders Anxiousness	10.0% 1/10 • Adverse events were collected from baseline to 1 month post-treatment All adverse events were self-reported according to a Side Effects Questionnaire administered at each visit.	16.7% 1/6 • Adverse events were collected from baseline to 1 month post-treatment All adverse events were self-reported according to a Side Effects Questionnaire administered at each visit.	0.00% 0/6 • Adverse events were collected from baseline to 1 month post-treatment All adverse events were self-reported according to a Side Effects Questionnaire administered at each visit.
Nervous system disorders Dizziness	10.0% 1/10 • Adverse events were collected from baseline to 1 month post-treatment All adverse events were self-reported according to a Side Effects Questionnaire administered at each visit.	16.7% 1/6 • Adverse events were collected from baseline to 1 month post-treatment All adverse events were self-reported according to a Side Effects Questionnaire administered at each visit.	0.00% 0/6 • Adverse events were collected from baseline to 1 month post-treatment All adverse events were self-reported according to a Side Effects Questionnaire administered at each visit.
Psychiatric disorders Depression	0.00% 0/10 • Adverse events were collected from baseline to 1 month post-treatment All adverse events were self-reported according to a Side Effects Questionnaire administered at each visit.	16.7% 1/6 • Adverse events were collected from baseline to 1 month post-treatment All adverse events were self-reported according to a Side Effects Questionnaire administered at each visit.	0.00% 0/6 • Adverse events were collected from baseline to 1 month post-treatment All adverse events were self-reported according to a Side Effects Questionnaire administered at each visit.
Musculoskeletal and connective tissue disorders Achiness	10.0% 1/10 • Adverse events were collected from baseline to 1 month post-treatment All adverse events were self-reported according to a Side Effects Questionnaire administered at each visit.	0.00% 0/6 • Adverse events were collected from baseline to 1 month post-treatment All adverse events were self-reported according to a Side Effects Questionnaire administered at each visit.	0.00% 0/6 • Adverse events were collected from baseline to 1 month post-treatment All adverse events were self-reported according to a Side Effects Questionnaire administered at each visit.
Musculoskeletal and connective tissue disorders Muscle Heaviness	10.0% 1/10 • Adverse events were collected from baseline to 1 month post-treatment All adverse events were self-reported according to a Side Effects Questionnaire administered at each visit.	0.00% 0/6 • Adverse events were collected from baseline to 1 month post-treatment All adverse events were self-reported according to a Side Effects Questionnaire administered at each visit.	0.00% 0/6 • Adverse events were collected from baseline to 1 month post-treatment All adverse events were self-reported according to a Side Effects Questionnaire administered at each visit.