Trial Outcomes & Findings for Latent Aging Mechanisms in Pain and Sleep (NCT NCT04683640)

Last Updated: 2025-07-18

Results Overview

The Pittsburgh Sleep Quality Index (PSQI) is a self-report questionnaire that assesses sleep quality over the past month. It consists of 19 items grouped into seven components. Each component is scored from 0 to 3, and the component scores are summed to yield a global total score ranging from 0 to 21. Higher scores indicate worse sleep quality. A total score greater than 5 is typically used to distinguish poor sleepers from good sleepers.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

33 participants

Primary outcome timeframe

PSQI was administered at baseline

Results posted on

2025-07-18

Participant Flow

All participants completed a screening visit and provided written informed consent before randomization. No run-in or washout phases were implemented before treatment initiation.

Participant milestones

Participant milestones
Measure	PLACEBO Participants self-administered Placebo (microcrystalline cellulose) capsules (two capsules) daily at home at 08:00 pm for 4 weeks.	GABA Participants self-administered PharmaGABA-250 (gamma-aminobutyric acid 250 mg/cap) 500 mg orally (two 250 mg capsules) daily at home at 08:00 pm for 4 weeks.
Overall Study STARTED	15	18
Overall Study COMPLETED	13	17
Overall Study NOT COMPLETED	2	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Latent Aging Mechanisms in Pain and Sleep

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	PLACEBO n=15 Participants Participants self-administered Placebo (microcrystalline cellulose) capsules (two capsules) daily at home at 08:00 pm for 4 weeks.	GABA n=18 Participants Participants self-administered PharmaGABA-250 (gamma-aminobutyric acid 250 mg/cap) 500 mg orally (two 250 mg capsules) daily at home at 08:00 pm for 4 weeks.	Total n=33 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants	6 Participants n=7 Participants	9 Participants n=5 Participants
Age, Categorical >=65 years	12 Participants n=5 Participants	12 Participants n=7 Participants	24 Participants n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants	13 Participants n=7 Participants	26 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	15 Participants n=5 Participants	17 Participants n=7 Participants	32 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) White	14 Participants n=5 Participants	16 Participants n=7 Participants	30 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	15 Participants n=5 Participants	18 Participants n=7 Participants	33 Participants n=5 Participants
The Pittsburgh Sleep Quality Index (PSQI)	11.20 Units on a scale (0-21). STANDARD_DEVIATION 4.18 • n=5 Participants	9.78 Units on a scale (0-21). STANDARD_DEVIATION 3.02 • n=7 Participants	10.43 Units on a scale (0-21). STANDARD_DEVIATION 3.59 • n=5 Participants

PRIMARY outcome

Timeframe: PSQI was administered at baseline

Population: Baseline characteristics for the Pittsburgh Sleep Quality Index (PSQI) are reported for participants who completed the baseline assessment and had complete PSQI data.

Outcome measures

Outcome measures
Measure	PLACEBO n=15 Participants Participants self-administered Placebo (microcrystalline cellulose) capsules (two capsules) daily at home at 08:00 pm for 4 weeks.	GABA n=18 Participants Participants self-administered PharmaGABA-250 (gamma-aminobutyric acid 250 mg/cap) 500 mg orally (two 250 mg capsules) daily at home at 08:00 pm for 4 weeks.
The Pittsburgh Sleep Quality Index (PSQI): PSQI Total Score at Baseline	11.20 Score on scale Standard Deviation 4.18	9.78 Score on scale Standard Deviation 3.02

PRIMARY outcome

Timeframe: PSQI was administered immediately after completing the 4-week intervention

Population: The number of participants analyzed post-intervention differs from the baseline assessment due to missing data. Two participants in Group A did not complete the PSQI at the post-intervention time point and were therefore excluded from the post-intervention analysis. All other participants included had complete data.

Outcome measures

Outcome measures
Measure	PLACEBO n=13 Participants Participants self-administered Placebo (microcrystalline cellulose) capsules (two capsules) daily at home at 08:00 pm for 4 weeks.	GABA n=18 Participants Participants self-administered PharmaGABA-250 (gamma-aminobutyric acid 250 mg/cap) 500 mg orally (two 250 mg capsules) daily at home at 08:00 pm for 4 weeks.
The Pittsburgh Sleep Quality Index (PSQI): PSQI Total Score at Post-Intervention	8.08 Score on scale Standard Deviation 3.59	7.89 Score on scale Standard Deviation 3.23

PRIMARY outcome

Timeframe: VDS was administered at baseline

Population: The analysis population for the Verbal Descriptor Scale (VDS) at baseline includes all participants who were assigned to Group A (n=15) and Group B (n=18), as all completed the baseline assessment.

The Verbal Descriptor Scale (VDS) is a validated self-report measure of pain intensity, commonly used in older adults. Participants are asked to select the descriptor that best represents their current pain level from six options: No pain, Mild, Moderate, Severe, Very severe, and Worst possible pain. Each descriptor corresponds to a numeric value from 0 to 5, with higher scores indicating greater pain intensity.

Outcome measures

Outcome measures
Measure	PLACEBO n=15 Participants Participants self-administered Placebo (microcrystalline cellulose) capsules (two capsules) daily at home at 08:00 pm for 4 weeks.	GABA n=18 Participants Participants self-administered PharmaGABA-250 (gamma-aminobutyric acid 250 mg/cap) 500 mg orally (two 250 mg capsules) daily at home at 08:00 pm for 4 weeks.
Verbal Descriptor Scale (VDS) at Baseline	2.00 Scores on a scale Interval 1.0 to 2.0	1.50 Scores on a scale Interval 1.0 to 2.0

PRIMARY outcome

Timeframe: VDS was administered immediately after completing the 4-week intervention

Population: The number of participants analyzed post-intervention differs from the baseline assessment due to missing data. Two participants in Group A did not complete the VDS at the post-intervention time point and were therefore excluded from the post-intervention analysis. All other participants included had complete data.

Outcome measures

Outcome measures
Measure	PLACEBO n=13 Participants Participants self-administered Placebo (microcrystalline cellulose) capsules (two capsules) daily at home at 08:00 pm for 4 weeks.	GABA n=18 Participants Participants self-administered PharmaGABA-250 (gamma-aminobutyric acid 250 mg/cap) 500 mg orally (two 250 mg capsules) daily at home at 08:00 pm for 4 weeks.
Verbal Descriptor Scale (VDS) at Post-Intervention	1 Score on scale Interval 0.5 to 2.0	1 Score on scale Interval 1.0 to 2.0

PRIMARY outcome

Timeframe: WOMAC was administered at baseline.

Population: The analysis population for the WOMAC at baseline includes all participants who were assigned to Group A (n=15) and Group B (n=18), as all completed the baseline assessment.

The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) is a validated self-report questionnaire that assesses pain, stiffness, and physical function in individuals with musculoskeletal conditions. It includes 24 items scored on a 5-point Likert scale (0 = none to 4 = extreme), producing subscale scores and a total score. The total WOMAC score ranges from 0 to 96, with higher scores indicating worse symptoms and functional limitations.

Outcome measures

Outcome measures
Measure	PLACEBO n=15 Participants Participants self-administered Placebo (microcrystalline cellulose) capsules (two capsules) daily at home at 08:00 pm for 4 weeks.	GABA n=18 Participants Participants self-administered PharmaGABA-250 (gamma-aminobutyric acid 250 mg/cap) 500 mg orally (two 250 mg capsules) daily at home at 08:00 pm for 4 weeks.
The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at Baseline	33.83 Score on scale Standard Deviation 18.98	34.77 Score on scale Standard Deviation 18.61

PRIMARY outcome

Timeframe: WOMAC was administered after completing the 4-week intervention

Outcome measures

Outcome measures
Measure	PLACEBO n=15 Participants Participants self-administered Placebo (microcrystalline cellulose) capsules (two capsules) daily at home at 08:00 pm for 4 weeks.	GABA n=18 Participants Participants self-administered PharmaGABA-250 (gamma-aminobutyric acid 250 mg/cap) 500 mg orally (two 250 mg capsules) daily at home at 08:00 pm for 4 weeks.
The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at Post-Intervention	22.92 Score on scale Standard Deviation 17.98	34.87 Score on scale Standard Deviation 19.41

SECONDARY outcome

Timeframe: Baseline

Population: The number of participants analyzed differs from the number of participants assigned to the group due to missing data. One participant in Group B did not complete the SF-MPQ-2 at baseline time point and was, therefore, excluded from the baseline analysis. All other participants included had complete data.

The Short-Form McGill Pain Questionnaire-2 (SF-MPQ-2) is a validated 22-item self-report instrument that assesses the multidimensional experience of pain. Items are grouped into four subscales-continuous, intermittent, neuropathic, and affective pain-and each item is rated from 0 (no pain) to 10 (worst possible pain) based on pain intensity over the past week. The total score is calculated as the average of all 22 item scores, with higher scores indicating greater pain severity.

Outcome measures

Outcome measures
Measure	PLACEBO n=15 Participants Participants self-administered Placebo (microcrystalline cellulose) capsules (two capsules) daily at home at 08:00 pm for 4 weeks.	GABA n=17 Participants Participants self-administered PharmaGABA-250 (gamma-aminobutyric acid 250 mg/cap) 500 mg orally (two 250 mg capsules) daily at home at 08:00 pm for 4 weeks.
Short-Form McGill Pain Questionnaire-2 (SF-MPQ-2) Total Score at Baseline	2.41 Score on scale Standard Deviation 1.63	2.21 Score on scale Standard Deviation 1.62

SECONDARY outcome

Timeframe: Immediately post-intervention (4 weeks)

Population: The number of participants analyzed post-intervention differs from the baseline assessment due to missing data. Two participants in Group A did not complete the SF-MPQ-2 at the post-intervention time point and were, therefore, excluded from the post-intervention analysis. All other participants included had complete data.

Outcome measures

Outcome measures
Measure	PLACEBO n=13 Participants Participants self-administered Placebo (microcrystalline cellulose) capsules (two capsules) daily at home at 08:00 pm for 4 weeks.	GABA n=18 Participants Participants self-administered PharmaGABA-250 (gamma-aminobutyric acid 250 mg/cap) 500 mg orally (two 250 mg capsules) daily at home at 08:00 pm for 4 weeks.
Short-Form McGill Pain Questionnaire-2 (SF-MPQ-2) Total Score at Post-Intervention	1.43 Score on scale Standard Deviation 1.14	1.77 Score on scale Standard Deviation 1.36

SECONDARY outcome

Timeframe: Baseline

The PainDETECT Questionnaire is a validated self-report instrument used to assess the likelihood of a neuropathic pain component in individuals with chronic pain. It includes 9 items that assess pain intensity, pain patterns, and sensory descriptors. The total score ranges from -1 to 38, with higher scores indicating a greater probability of neuropathic pain. A score ≥19 suggests likely neuropathic pain, 13-18 indicates possible neuropathic pain, and ≤12 suggests that neuropathic pain is unlikely.

Outcome measures

Outcome measures
Measure	PLACEBO n=15 Participants Participants self-administered Placebo (microcrystalline cellulose) capsules (two capsules) daily at home at 08:00 pm for 4 weeks.	GABA n=18 Participants Participants self-administered PharmaGABA-250 (gamma-aminobutyric acid 250 mg/cap) 500 mg orally (two 250 mg capsules) daily at home at 08:00 pm for 4 weeks.
Pain Detect at Baseline	9.23 Score on scale Standard Deviation 5.70	9.39 Score on scale Standard Deviation 6.89

SECONDARY outcome

Timeframe: Immediately post-intervention (4 weeks)

Population: The number of participants analyzed post-intervention differs from the baseline assessment due to missing data. Two participants in Group A did not complete the Pain Detect at the post-intervention time point and were, therefore, excluded from the post-intervention analysis. All other participants included had complete data.

Outcome measures

Outcome measures
Measure	PLACEBO n=13 Participants Participants self-administered Placebo (microcrystalline cellulose) capsules (two capsules) daily at home at 08:00 pm for 4 weeks.	GABA n=18 Participants Participants self-administered PharmaGABA-250 (gamma-aminobutyric acid 250 mg/cap) 500 mg orally (two 250 mg capsules) daily at home at 08:00 pm for 4 weeks.
Pain Detect at Post-Intervention	6.54 Score on scale Standard Deviation 5.17	8.33 Score on scale Standard Deviation 6.27

SECONDARY outcome

Timeframe: Baseline

Population: The number of participants analyzed differs from the number of participants assigned to the group due to missing data. Three participants in Group A, and two in Group B, did not complete the FOSQ-10 at the baseline time point and were, therefore, excluded from the baseline analysis. All other participants included had complete data.

The Functional Outcomes of Sleep Questionnaire-10 (FOSQ-10) is a 10-item self-report instrument that assesses the impact of excessive daytime sleepiness on daily functioning across five domains. Each item is rated on a 4-point Likert scale from 1 (extreme difficulty) to 4 (no difficulty). The total score is calculated by averaging items within each domain and summing the domain means. Total scores range from 5 to 20, with higher scores indicating better functional status and less impairment.

Outcome measures

Outcome measures
Measure	PLACEBO n=12 Participants Participants self-administered Placebo (microcrystalline cellulose) capsules (two capsules) daily at home at 08:00 pm for 4 weeks.	GABA n=16 Participants Participants self-administered PharmaGABA-250 (gamma-aminobutyric acid 250 mg/cap) 500 mg orally (two 250 mg capsules) daily at home at 08:00 pm for 4 weeks.
Functional Outcomes of Sleep Questionnaire - 10 Items (FOSQ-10) at Baseline	17.54 Score on scale Standard Deviation 1.28	16.58 Score on scale Standard Deviation 2.84

SECONDARY outcome

Timeframe: Immediately post-intervention (4 weeks)

Population: The number of participants analyzed post-intervention differs from the baseline assessment due to missing data. Two participants in Group A did not complete the FOSQ-10 at the post-intervention time point and were therefore excluded from the post-intervention analysis. All other participants included had complete data.

Outcome measures

Outcome measures
Measure	PLACEBO n=12 Participants Participants self-administered Placebo (microcrystalline cellulose) capsules (two capsules) daily at home at 08:00 pm for 4 weeks.	GABA n=18 Participants Participants self-administered PharmaGABA-250 (gamma-aminobutyric acid 250 mg/cap) 500 mg orally (two 250 mg capsules) daily at home at 08:00 pm for 4 weeks.
Functional Outcomes of Sleep Questionnaire - 10 Items (FOSQ-10) at Post-Intervention	12.60 Score on scale Standard Deviation 2.70	12.48 Score on scale Standard Deviation 2.65

SECONDARY outcome

Timeframe: Baseline

Population: The number of participants analyzed differs from the number of participants assigned to the group due to missing data. Three participants in Group A, and two in Group B, did not complete the ESS at the baseline time point and were, therefore, excluded from the baseline analysis. All other participants included had complete data.

The Epworth Sleepiness Scale (ESS) is an 8-item self-report questionnaire that assesses the likelihood of dozing off or falling asleep during common daily activities. Each item is scored from 0 (would never doze) to 3 (high chance of dozing). The total score is calculated by summing the scores across all 8 items, yielding a total range of 0 to 24, with higher scores indicating greater levels of daytime sleepiness.

Outcome measures

Outcome measures
Measure	PLACEBO n=12 Participants Participants self-administered Placebo (microcrystalline cellulose) capsules (two capsules) daily at home at 08:00 pm for 4 weeks.	GABA n=16 Participants Participants self-administered PharmaGABA-250 (gamma-aminobutyric acid 250 mg/cap) 500 mg orally (two 250 mg capsules) daily at home at 08:00 pm for 4 weeks.
Epworth Sleepiness Scale (ESS) at Baseline	6.67 Score on scale Standard Deviation 3.03	8.56 Score on scale Standard Deviation 4.13

SECONDARY outcome

Timeframe: Immediately post-intervention (4 weeks)

Population: The number of participants analyzed differs from the number of participants assigned to the group due to missing data. Three participants in Group A did not complete the ESS at the post-intervention time point and were, therefore, excluded from the post-intervention analysis. All other participants included had complete data.

Outcome measures

Outcome measures
Measure	PLACEBO n=12 Participants Participants self-administered Placebo (microcrystalline cellulose) capsules (two capsules) daily at home at 08:00 pm for 4 weeks.	GABA n=18 Participants Participants self-administered PharmaGABA-250 (gamma-aminobutyric acid 250 mg/cap) 500 mg orally (two 250 mg capsules) daily at home at 08:00 pm for 4 weeks.
Epworth Sleepiness Scale (ESS) at Post-Intervention	7.08 Score on scale Standard Deviation 4.44	7.56 Score on scale Standard Deviation 5

Adverse Events

PLACEBO

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

GABA

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Yenisel Cruz-Almeida

University of Florida

Phone: (352) 294-5845

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Other adverse events
Measure	PLACEBO n=15 participants at risk Participants self-administered Placebo (microcrystalline cellulose) capsules (two capsules) daily at home at 08:00 pm for 4 weeks.	GABA n=18 participants at risk Participants self-administered PharmaGABA-250 (gamma-aminobutyric acid 250 mg/cap) 500 mg orally (two 250 mg capsules) daily at home at 08:00 pm for 4 weeks.
Respiratory, thoracic and mediastinal disorders Shortness of breath	6.7% 1/15 • Number of events 1 • From the start of the intervention through 3 months post-intervention. Adverse events were actively monitored weekly during the 4-week treatment phase and followed up for an additional 3 months after study completion Adverse events in this study were defined as any unfavorable or unintended signs, symptoms, or conditions reported by participants during the study period, regardless of relatedness to the intervention. Adverse events were systematically assessed through weekly check-in calls during the 4-week intervention phase and continued via follow-up for 3 months post-intervention. All events reported were non-serious, local, and categorized as possibly related to the study procedures.	0.00% 0/18 • From the start of the intervention through 3 months post-intervention. Adverse events were actively monitored weekly during the 4-week treatment phase and followed up for an additional 3 months after study completion Adverse events in this study were defined as any unfavorable or unintended signs, symptoms, or conditions reported by participants during the study period, regardless of relatedness to the intervention. Adverse events were systematically assessed through weekly check-in calls during the 4-week intervention phase and continued via follow-up for 3 months post-intervention. All events reported were non-serious, local, and categorized as possibly related to the study procedures.
Gastrointestinal disorders Abdominal/stomach pain	20.0% 3/15 • Number of events 3 • From the start of the intervention through 3 months post-intervention. Adverse events were actively monitored weekly during the 4-week treatment phase and followed up for an additional 3 months after study completion Adverse events in this study were defined as any unfavorable or unintended signs, symptoms, or conditions reported by participants during the study period, regardless of relatedness to the intervention. Adverse events were systematically assessed through weekly check-in calls during the 4-week intervention phase and continued via follow-up for 3 months post-intervention. All events reported were non-serious, local, and categorized as possibly related to the study procedures.	33.3% 6/18 • Number of events 6 • From the start of the intervention through 3 months post-intervention. Adverse events were actively monitored weekly during the 4-week treatment phase and followed up for an additional 3 months after study completion Adverse events in this study were defined as any unfavorable or unintended signs, symptoms, or conditions reported by participants during the study period, regardless of relatedness to the intervention. Adverse events were systematically assessed through weekly check-in calls during the 4-week intervention phase and continued via follow-up for 3 months post-intervention. All events reported were non-serious, local, and categorized as possibly related to the study procedures.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/15 • From the start of the intervention through 3 months post-intervention. Adverse events were actively monitored weekly during the 4-week treatment phase and followed up for an additional 3 months after study completion Adverse events in this study were defined as any unfavorable or unintended signs, symptoms, or conditions reported by participants during the study period, regardless of relatedness to the intervention. Adverse events were systematically assessed through weekly check-in calls during the 4-week intervention phase and continued via follow-up for 3 months post-intervention. All events reported were non-serious, local, and categorized as possibly related to the study procedures.	5.6% 1/18 • Number of events 1 • From the start of the intervention through 3 months post-intervention. Adverse events were actively monitored weekly during the 4-week treatment phase and followed up for an additional 3 months after study completion Adverse events in this study were defined as any unfavorable or unintended signs, symptoms, or conditions reported by participants during the study period, regardless of relatedness to the intervention. Adverse events were systematically assessed through weekly check-in calls during the 4-week intervention phase and continued via follow-up for 3 months post-intervention. All events reported were non-serious, local, and categorized as possibly related to the study procedures.
Nervous system disorders Balance problems	0.00% 0/15 • From the start of the intervention through 3 months post-intervention. Adverse events were actively monitored weekly during the 4-week treatment phase and followed up for an additional 3 months after study completion Adverse events in this study were defined as any unfavorable or unintended signs, symptoms, or conditions reported by participants during the study period, regardless of relatedness to the intervention. Adverse events were systematically assessed through weekly check-in calls during the 4-week intervention phase and continued via follow-up for 3 months post-intervention. All events reported were non-serious, local, and categorized as possibly related to the study procedures.	50.0% 9/18 • Number of events 9 • From the start of the intervention through 3 months post-intervention. Adverse events were actively monitored weekly during the 4-week treatment phase and followed up for an additional 3 months after study completion Adverse events in this study were defined as any unfavorable or unintended signs, symptoms, or conditions reported by participants during the study period, regardless of relatedness to the intervention. Adverse events were systematically assessed through weekly check-in calls during the 4-week intervention phase and continued via follow-up for 3 months post-intervention. All events reported were non-serious, local, and categorized as possibly related to the study procedures.
Eye disorders Blurred vision	13.3% 2/15 • Number of events 2 • From the start of the intervention through 3 months post-intervention. Adverse events were actively monitored weekly during the 4-week treatment phase and followed up for an additional 3 months after study completion Adverse events in this study were defined as any unfavorable or unintended signs, symptoms, or conditions reported by participants during the study period, regardless of relatedness to the intervention. Adverse events were systematically assessed through weekly check-in calls during the 4-week intervention phase and continued via follow-up for 3 months post-intervention. All events reported were non-serious, local, and categorized as possibly related to the study procedures.	27.8% 5/18 • Number of events 5 • From the start of the intervention through 3 months post-intervention. Adverse events were actively monitored weekly during the 4-week treatment phase and followed up for an additional 3 months after study completion Adverse events in this study were defined as any unfavorable or unintended signs, symptoms, or conditions reported by participants during the study period, regardless of relatedness to the intervention. Adverse events were systematically assessed through weekly check-in calls during the 4-week intervention phase and continued via follow-up for 3 months post-intervention. All events reported were non-serious, local, and categorized as possibly related to the study procedures.
Social circumstances Causing difficulty sleeping longer	6.7% 1/15 • Number of events 1 • From the start of the intervention through 3 months post-intervention. Adverse events were actively monitored weekly during the 4-week treatment phase and followed up for an additional 3 months after study completion Adverse events in this study were defined as any unfavorable or unintended signs, symptoms, or conditions reported by participants during the study period, regardless of relatedness to the intervention. Adverse events were systematically assessed through weekly check-in calls during the 4-week intervention phase and continued via follow-up for 3 months post-intervention. All events reported were non-serious, local, and categorized as possibly related to the study procedures.	0.00% 0/18 • From the start of the intervention through 3 months post-intervention. Adverse events were actively monitored weekly during the 4-week treatment phase and followed up for an additional 3 months after study completion Adverse events in this study were defined as any unfavorable or unintended signs, symptoms, or conditions reported by participants during the study period, regardless of relatedness to the intervention. Adverse events were systematically assessed through weekly check-in calls during the 4-week intervention phase and continued via follow-up for 3 months post-intervention. All events reported were non-serious, local, and categorized as possibly related to the study procedures.
Metabolism and nutrition disorders Change in appetite	20.0% 3/15 • Number of events 3 • From the start of the intervention through 3 months post-intervention. Adverse events were actively monitored weekly during the 4-week treatment phase and followed up for an additional 3 months after study completion Adverse events in this study were defined as any unfavorable or unintended signs, symptoms, or conditions reported by participants during the study period, regardless of relatedness to the intervention. Adverse events were systematically assessed through weekly check-in calls during the 4-week intervention phase and continued via follow-up for 3 months post-intervention. All events reported were non-serious, local, and categorized as possibly related to the study procedures.	22.2% 4/18 • Number of events 4 • From the start of the intervention through 3 months post-intervention. Adverse events were actively monitored weekly during the 4-week treatment phase and followed up for an additional 3 months after study completion Adverse events in this study were defined as any unfavorable or unintended signs, symptoms, or conditions reported by participants during the study period, regardless of relatedness to the intervention. Adverse events were systematically assessed through weekly check-in calls during the 4-week intervention phase and continued via follow-up for 3 months post-intervention. All events reported were non-serious, local, and categorized as possibly related to the study procedures.
Psychiatric disorders Feelings of stress or anxiety	53.3% 8/15 • Number of events 8 • From the start of the intervention through 3 months post-intervention. Adverse events were actively monitored weekly during the 4-week treatment phase and followed up for an additional 3 months after study completion Adverse events in this study were defined as any unfavorable or unintended signs, symptoms, or conditions reported by participants during the study period, regardless of relatedness to the intervention. Adverse events were systematically assessed through weekly check-in calls during the 4-week intervention phase and continued via follow-up for 3 months post-intervention. All events reported were non-serious, local, and categorized as possibly related to the study procedures.	44.4% 8/18 • Number of events 8 • From the start of the intervention through 3 months post-intervention. Adverse events were actively monitored weekly during the 4-week treatment phase and followed up for an additional 3 months after study completion Adverse events in this study were defined as any unfavorable or unintended signs, symptoms, or conditions reported by participants during the study period, regardless of relatedness to the intervention. Adverse events were systematically assessed through weekly check-in calls during the 4-week intervention phase and continued via follow-up for 3 months post-intervention. All events reported were non-serious, local, and categorized as possibly related to the study procedures.
Endocrine disorders Glucose high/ thirsty	6.7% 1/15 • Number of events 1 • From the start of the intervention through 3 months post-intervention. Adverse events were actively monitored weekly during the 4-week treatment phase and followed up for an additional 3 months after study completion Adverse events in this study were defined as any unfavorable or unintended signs, symptoms, or conditions reported by participants during the study period, regardless of relatedness to the intervention. Adverse events were systematically assessed through weekly check-in calls during the 4-week intervention phase and continued via follow-up for 3 months post-intervention. All events reported were non-serious, local, and categorized as possibly related to the study procedures.	5.6% 1/18 • Number of events 1 • From the start of the intervention through 3 months post-intervention. Adverse events were actively monitored weekly during the 4-week treatment phase and followed up for an additional 3 months after study completion Adverse events in this study were defined as any unfavorable or unintended signs, symptoms, or conditions reported by participants during the study period, regardless of relatedness to the intervention. Adverse events were systematically assessed through weekly check-in calls during the 4-week intervention phase and continued via follow-up for 3 months post-intervention. All events reported were non-serious, local, and categorized as possibly related to the study procedures.
Cardiac disorders Heart rate changes/palpitations	13.3% 2/15 • Number of events 2 • From the start of the intervention through 3 months post-intervention. Adverse events were actively monitored weekly during the 4-week treatment phase and followed up for an additional 3 months after study completion Adverse events in this study were defined as any unfavorable or unintended signs, symptoms, or conditions reported by participants during the study period, regardless of relatedness to the intervention. Adverse events were systematically assessed through weekly check-in calls during the 4-week intervention phase and continued via follow-up for 3 months post-intervention. All events reported were non-serious, local, and categorized as possibly related to the study procedures.	27.8% 5/18 • Number of events 5 • From the start of the intervention through 3 months post-intervention. Adverse events were actively monitored weekly during the 4-week treatment phase and followed up for an additional 3 months after study completion Adverse events in this study were defined as any unfavorable or unintended signs, symptoms, or conditions reported by participants during the study period, regardless of relatedness to the intervention. Adverse events were systematically assessed through weekly check-in calls during the 4-week intervention phase and continued via follow-up for 3 months post-intervention. All events reported were non-serious, local, and categorized as possibly related to the study procedures.
Musculoskeletal and connective tissue disorders Left shoulder pain	6.7% 1/15 • Number of events 1 • From the start of the intervention through 3 months post-intervention. Adverse events were actively monitored weekly during the 4-week treatment phase and followed up for an additional 3 months after study completion Adverse events in this study were defined as any unfavorable or unintended signs, symptoms, or conditions reported by participants during the study period, regardless of relatedness to the intervention. Adverse events were systematically assessed through weekly check-in calls during the 4-week intervention phase and continued via follow-up for 3 months post-intervention. All events reported were non-serious, local, and categorized as possibly related to the study procedures.	0.00% 0/18 • From the start of the intervention through 3 months post-intervention. Adverse events were actively monitored weekly during the 4-week treatment phase and followed up for an additional 3 months after study completion Adverse events in this study were defined as any unfavorable or unintended signs, symptoms, or conditions reported by participants during the study period, regardless of relatedness to the intervention. Adverse events were systematically assessed through weekly check-in calls during the 4-week intervention phase and continued via follow-up for 3 months post-intervention. All events reported were non-serious, local, and categorized as possibly related to the study procedures.
Nervous system disorders Light-headedness/vertigo	40.0% 6/15 • Number of events 6 • From the start of the intervention through 3 months post-intervention. Adverse events were actively monitored weekly during the 4-week treatment phase and followed up for an additional 3 months after study completion Adverse events in this study were defined as any unfavorable or unintended signs, symptoms, or conditions reported by participants during the study period, regardless of relatedness to the intervention. Adverse events were systematically assessed through weekly check-in calls during the 4-week intervention phase and continued via follow-up for 3 months post-intervention. All events reported were non-serious, local, and categorized as possibly related to the study procedures.	44.4% 8/18 • Number of events 8 • From the start of the intervention through 3 months post-intervention. Adverse events were actively monitored weekly during the 4-week treatment phase and followed up for an additional 3 months after study completion Adverse events in this study were defined as any unfavorable or unintended signs, symptoms, or conditions reported by participants during the study period, regardless of relatedness to the intervention. Adverse events were systematically assessed through weekly check-in calls during the 4-week intervention phase and continued via follow-up for 3 months post-intervention. All events reported were non-serious, local, and categorized as possibly related to the study procedures.
Gastrointestinal disorders Nausea/vomiting	6.7% 1/15 • Number of events 1 • From the start of the intervention through 3 months post-intervention. Adverse events were actively monitored weekly during the 4-week treatment phase and followed up for an additional 3 months after study completion Adverse events in this study were defined as any unfavorable or unintended signs, symptoms, or conditions reported by participants during the study period, regardless of relatedness to the intervention. Adverse events were systematically assessed through weekly check-in calls during the 4-week intervention phase and continued via follow-up for 3 months post-intervention. All events reported were non-serious, local, and categorized as possibly related to the study procedures.	22.2% 4/18 • Number of events 4 • From the start of the intervention through 3 months post-intervention. Adverse events were actively monitored weekly during the 4-week treatment phase and followed up for an additional 3 months after study completion Adverse events in this study were defined as any unfavorable or unintended signs, symptoms, or conditions reported by participants during the study period, regardless of relatedness to the intervention. Adverse events were systematically assessed through weekly check-in calls during the 4-week intervention phase and continued via follow-up for 3 months post-intervention. All events reported were non-serious, local, and categorized as possibly related to the study procedures.
Musculoskeletal and connective tissue disorders Right leg cramps	0.00% 0/15 • From the start of the intervention through 3 months post-intervention. Adverse events were actively monitored weekly during the 4-week treatment phase and followed up for an additional 3 months after study completion Adverse events in this study were defined as any unfavorable or unintended signs, symptoms, or conditions reported by participants during the study period, regardless of relatedness to the intervention. Adverse events were systematically assessed through weekly check-in calls during the 4-week intervention phase and continued via follow-up for 3 months post-intervention. All events reported were non-serious, local, and categorized as possibly related to the study procedures.	5.6% 1/18 • Number of events 1 • From the start of the intervention through 3 months post-intervention. Adverse events were actively monitored weekly during the 4-week treatment phase and followed up for an additional 3 months after study completion Adverse events in this study were defined as any unfavorable or unintended signs, symptoms, or conditions reported by participants during the study period, regardless of relatedness to the intervention. Adverse events were systematically assessed through weekly check-in calls during the 4-week intervention phase and continued via follow-up for 3 months post-intervention. All events reported were non-serious, local, and categorized as possibly related to the study procedures.
Skin and subcutaneous tissue disorders Skin rash/itching	13.3% 2/15 • Number of events 2 • From the start of the intervention through 3 months post-intervention. Adverse events were actively monitored weekly during the 4-week treatment phase and followed up for an additional 3 months after study completion Adverse events in this study were defined as any unfavorable or unintended signs, symptoms, or conditions reported by participants during the study period, regardless of relatedness to the intervention. Adverse events were systematically assessed through weekly check-in calls during the 4-week intervention phase and continued via follow-up for 3 months post-intervention. All events reported were non-serious, local, and categorized as possibly related to the study procedures.	27.8% 5/18 • Number of events 5 • From the start of the intervention through 3 months post-intervention. Adverse events were actively monitored weekly during the 4-week treatment phase and followed up for an additional 3 months after study completion Adverse events in this study were defined as any unfavorable or unintended signs, symptoms, or conditions reported by participants during the study period, regardless of relatedness to the intervention. Adverse events were systematically assessed through weekly check-in calls during the 4-week intervention phase and continued via follow-up for 3 months post-intervention. All events reported were non-serious, local, and categorized as possibly related to the study procedures.
Ear and labyrinth disorders Tinnitus	0.00% 0/15 • From the start of the intervention through 3 months post-intervention. Adverse events were actively monitored weekly during the 4-week treatment phase and followed up for an additional 3 months after study completion Adverse events in this study were defined as any unfavorable or unintended signs, symptoms, or conditions reported by participants during the study period, regardless of relatedness to the intervention. Adverse events were systematically assessed through weekly check-in calls during the 4-week intervention phase and continued via follow-up for 3 months post-intervention. All events reported were non-serious, local, and categorized as possibly related to the study procedures.	5.6% 1/18 • Number of events 1 • From the start of the intervention through 3 months post-intervention. Adverse events were actively monitored weekly during the 4-week treatment phase and followed up for an additional 3 months after study completion Adverse events in this study were defined as any unfavorable or unintended signs, symptoms, or conditions reported by participants during the study period, regardless of relatedness to the intervention. Adverse events were systematically assessed through weekly check-in calls during the 4-week intervention phase and continued via follow-up for 3 months post-intervention. All events reported were non-serious, local, and categorized as possibly related to the study procedures.
Vascular disorders Changes in blood pressure	13.3% 2/15 • Number of events 2 • From the start of the intervention through 3 months post-intervention. Adverse events were actively monitored weekly during the 4-week treatment phase and followed up for an additional 3 months after study completion Adverse events in this study were defined as any unfavorable or unintended signs, symptoms, or conditions reported by participants during the study period, regardless of relatedness to the intervention. Adverse events were systematically assessed through weekly check-in calls during the 4-week intervention phase and continued via follow-up for 3 months post-intervention. All events reported were non-serious, local, and categorized as possibly related to the study procedures.	5.6% 1/18 • Number of events 1 • From the start of the intervention through 3 months post-intervention. Adverse events were actively monitored weekly during the 4-week treatment phase and followed up for an additional 3 months after study completion Adverse events in this study were defined as any unfavorable or unintended signs, symptoms, or conditions reported by participants during the study period, regardless of relatedness to the intervention. Adverse events were systematically assessed through weekly check-in calls during the 4-week intervention phase and continued via follow-up for 3 months post-intervention. All events reported were non-serious, local, and categorized as possibly related to the study procedures.
Psychiatric disorders Changes in mood	26.7% 4/15 • Number of events 4 • From the start of the intervention through 3 months post-intervention. Adverse events were actively monitored weekly during the 4-week treatment phase and followed up for an additional 3 months after study completion Adverse events in this study were defined as any unfavorable or unintended signs, symptoms, or conditions reported by participants during the study period, regardless of relatedness to the intervention. Adverse events were systematically assessed through weekly check-in calls during the 4-week intervention phase and continued via follow-up for 3 months post-intervention. All events reported were non-serious, local, and categorized as possibly related to the study procedures.	33.3% 6/18 • Number of events 6 • From the start of the intervention through 3 months post-intervention. Adverse events were actively monitored weekly during the 4-week treatment phase and followed up for an additional 3 months after study completion Adverse events in this study were defined as any unfavorable or unintended signs, symptoms, or conditions reported by participants during the study period, regardless of relatedness to the intervention. Adverse events were systematically assessed through weekly check-in calls during the 4-week intervention phase and continued via follow-up for 3 months post-intervention. All events reported were non-serious, local, and categorized as possibly related to the study procedures.
Gastrointestinal disorders Constipation	46.7% 7/15 • Number of events 7 • From the start of the intervention through 3 months post-intervention. Adverse events were actively monitored weekly during the 4-week treatment phase and followed up for an additional 3 months after study completion Adverse events in this study were defined as any unfavorable or unintended signs, symptoms, or conditions reported by participants during the study period, regardless of relatedness to the intervention. Adverse events were systematically assessed through weekly check-in calls during the 4-week intervention phase and continued via follow-up for 3 months post-intervention. All events reported were non-serious, local, and categorized as possibly related to the study procedures.	38.9% 7/18 • Number of events 7 • From the start of the intervention through 3 months post-intervention. Adverse events were actively monitored weekly during the 4-week treatment phase and followed up for an additional 3 months after study completion Adverse events in this study were defined as any unfavorable or unintended signs, symptoms, or conditions reported by participants during the study period, regardless of relatedness to the intervention. Adverse events were systematically assessed through weekly check-in calls during the 4-week intervention phase and continued via follow-up for 3 months post-intervention. All events reported were non-serious, local, and categorized as possibly related to the study procedures.
Gastrointestinal disorders Diarrhea	6.7% 1/15 • Number of events 1 • From the start of the intervention through 3 months post-intervention. Adverse events were actively monitored weekly during the 4-week treatment phase and followed up for an additional 3 months after study completion Adverse events in this study were defined as any unfavorable or unintended signs, symptoms, or conditions reported by participants during the study period, regardless of relatedness to the intervention. Adverse events were systematically assessed through weekly check-in calls during the 4-week intervention phase and continued via follow-up for 3 months post-intervention. All events reported were non-serious, local, and categorized as possibly related to the study procedures.	5.6% 1/18 • Number of events 1 • From the start of the intervention through 3 months post-intervention. Adverse events were actively monitored weekly during the 4-week treatment phase and followed up for an additional 3 months after study completion Adverse events in this study were defined as any unfavorable or unintended signs, symptoms, or conditions reported by participants during the study period, regardless of relatedness to the intervention. Adverse events were systematically assessed through weekly check-in calls during the 4-week intervention phase and continued via follow-up for 3 months post-intervention. All events reported were non-serious, local, and categorized as possibly related to the study procedures.
Nervous system disorders Drowsiness/sleepiness	73.3% 11/15 • Number of events 11 • From the start of the intervention through 3 months post-intervention. Adverse events were actively monitored weekly during the 4-week treatment phase and followed up for an additional 3 months after study completion Adverse events in this study were defined as any unfavorable or unintended signs, symptoms, or conditions reported by participants during the study period, regardless of relatedness to the intervention. Adverse events were systematically assessed through weekly check-in calls during the 4-week intervention phase and continued via follow-up for 3 months post-intervention. All events reported were non-serious, local, and categorized as possibly related to the study procedures.	61.1% 11/18 • Number of events 11 • From the start of the intervention through 3 months post-intervention. Adverse events were actively monitored weekly during the 4-week treatment phase and followed up for an additional 3 months after study completion Adverse events in this study were defined as any unfavorable or unintended signs, symptoms, or conditions reported by participants during the study period, regardless of relatedness to the intervention. Adverse events were systematically assessed through weekly check-in calls during the 4-week intervention phase and continued via follow-up for 3 months post-intervention. All events reported were non-serious, local, and categorized as possibly related to the study procedures.
General disorders Tired	6.7% 1/15 • Number of events 1 • From the start of the intervention through 3 months post-intervention. Adverse events were actively monitored weekly during the 4-week treatment phase and followed up for an additional 3 months after study completion Adverse events in this study were defined as any unfavorable or unintended signs, symptoms, or conditions reported by participants during the study period, regardless of relatedness to the intervention. Adverse events were systematically assessed through weekly check-in calls during the 4-week intervention phase and continued via follow-up for 3 months post-intervention. All events reported were non-serious, local, and categorized as possibly related to the study procedures.	0.00% 0/18 • From the start of the intervention through 3 months post-intervention. Adverse events were actively monitored weekly during the 4-week treatment phase and followed up for an additional 3 months after study completion Adverse events in this study were defined as any unfavorable or unintended signs, symptoms, or conditions reported by participants during the study period, regardless of relatedness to the intervention. Adverse events were systematically assessed through weekly check-in calls during the 4-week intervention phase and continued via follow-up for 3 months post-intervention. All events reported were non-serious, local, and categorized as possibly related to the study procedures.
Respiratory, thoracic and mediastinal disorders Dry throat	20.0% 3/15 • Number of events 3 • From the start of the intervention through 3 months post-intervention. Adverse events were actively monitored weekly during the 4-week treatment phase and followed up for an additional 3 months after study completion Adverse events in this study were defined as any unfavorable or unintended signs, symptoms, or conditions reported by participants during the study period, regardless of relatedness to the intervention. Adverse events were systematically assessed through weekly check-in calls during the 4-week intervention phase and continued via follow-up for 3 months post-intervention. All events reported were non-serious, local, and categorized as possibly related to the study procedures.	50.0% 9/18 • Number of events 9 • From the start of the intervention through 3 months post-intervention. Adverse events were actively monitored weekly during the 4-week treatment phase and followed up for an additional 3 months after study completion Adverse events in this study were defined as any unfavorable or unintended signs, symptoms, or conditions reported by participants during the study period, regardless of relatedness to the intervention. Adverse events were systematically assessed through weekly check-in calls during the 4-week intervention phase and continued via follow-up for 3 months post-intervention. All events reported were non-serious, local, and categorized as possibly related to the study procedures.
General disorders Fatigue	53.3% 8/15 • Number of events 8 • From the start of the intervention through 3 months post-intervention. Adverse events were actively monitored weekly during the 4-week treatment phase and followed up for an additional 3 months after study completion Adverse events in this study were defined as any unfavorable or unintended signs, symptoms, or conditions reported by participants during the study period, regardless of relatedness to the intervention. Adverse events were systematically assessed through weekly check-in calls during the 4-week intervention phase and continued via follow-up for 3 months post-intervention. All events reported were non-serious, local, and categorized as possibly related to the study procedures.	66.7% 12/18 • Number of events 12 • From the start of the intervention through 3 months post-intervention. Adverse events were actively monitored weekly during the 4-week treatment phase and followed up for an additional 3 months after study completion Adverse events in this study were defined as any unfavorable or unintended signs, symptoms, or conditions reported by participants during the study period, regardless of relatedness to the intervention. Adverse events were systematically assessed through weekly check-in calls during the 4-week intervention phase and continued via follow-up for 3 months post-intervention. All events reported were non-serious, local, and categorized as possibly related to the study procedures.