Trial Outcomes & Findings for Essential Oils for Enhancing QOL in ASD (NCT NCT02543203)

Last Updated: 2021-04-01

Results Overview

Pediatric Quality of Life Inventory (PedsQL) (Varni, Burwinkle, \& Seid, 2006). The Generic PedsQL Inventory is a caregiver-rated scale for children ages 2-12. The PedsQL Inventory for 2-4 year old children includes 21 items. The PedsQL Inventories for 5-12 year old children include 23-items. The PedsQL Inventories were designed to measure the core domains of health and their impact on the quality of life in children as outlined by the World Health Organization. The four sub-scales are Physical Functioning, Emotional Functioning, Social Functioning, and School Functioning. The summary scores include a total scale score and individual sub-scale scores. Higher scores on reversed scored items indicates better quality of life.The scores when reversed range from 0 to 100.Since there were an unequal number of items on the younger children's inventory, to be enrolled we used a cut-off of \> or = 1.5 item mean on the PedsQL Inventory, which indicated poorer quality of life.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

28 participants

Primary outcome timeframe

28 Weeks

Results posted on

2021-04-01

Participant Flow

Forty subjects were screened for eligibility between between July 22nd 2015 and June 22nd 2017, at the Ohio State University's Nisonger Center.

Of the 40 subjects screened, 28 were randomized to treatment order. Twelve subjects did not meet the study criteria. After randomization, one subject's caregiver revealed that she could not stop melatonin treatment and another caregiver withdrew because there was a death in the family. The modified intent to treat sample included 26 participants.

Participant milestones

Participant milestones
Measure	Reconnect, Then Comparator Participants received Reconnect each morning and evening for 3-months and then after a 1-month washout they received the comparator oil. In the morning the oil was administered topically. Participants were administered 1 drop to the back of the neck and 1 drop to the feet, to be rubbed in for 30 seconds to 1 minute. In the evening, before bedtime, the aromatic method was used. Caregivers diffused 8-12 drops of oil in water at night.	Coconut Oil Comparator, Then Reconnect Participants received the comparator oil each morning and evening for 3-months and then after a 1-month washout they received Reconnect. In the morning the oil was administered topically. Participants were administered 1 drop to the back of the neck and 1 drop to the feet, to be rubbed in for 30 seconds to 1 minute. In the evening, before bedtime, the aromatic method was used. Caregivers diffused 8-12 drops of oil in water at night.
Overall Study STARTED	13	15
Overall Study COMPLETED	7	10
Overall Study NOT COMPLETED	6	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Reconnect, Then Comparator Participants received Reconnect each morning and evening for 3-months and then after a 1-month washout they received the comparator oil. In the morning the oil was administered topically. Participants were administered 1 drop to the back of the neck and 1 drop to the feet, to be rubbed in for 30 seconds to 1 minute. In the evening, before bedtime, the aromatic method was used. Caregivers diffused 8-12 drops of oil in water at night.	Coconut Oil Comparator, Then Reconnect Participants received the comparator oil each morning and evening for 3-months and then after a 1-month washout they received Reconnect. In the morning the oil was administered topically. Participants were administered 1 drop to the back of the neck and 1 drop to the feet, to be rubbed in for 30 seconds to 1 minute. In the evening, before bedtime, the aromatic method was used. Caregivers diffused 8-12 drops of oil in water at night.
Overall Study Unpalatable Fragrance	2	2
Overall Study Lost to Follow-up	1	0
Overall Study Increased Irritability	1	0
Overall Study Family	1	2
Overall Study Negative Behavior	1	0
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Essential Oils for Enhancing QOL in ASD

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	A/C (Reconnect/Comparator) n=12 Participants Topical: Apply 1 drop to the back of the neck and 1 drop to the feet. Rub in the oil for 30 seconds to 1 minute. Each bottle has an orifice that allows the oil to be expelled drop by drop. Dilution is not required, except for the most sensitive skin. Apply in the morning. Aromatic Method: Diffuse one diffuser-full (8-12 drops of oil in water) at night.	C/A (Comparator/Reconnect) n=14 Participants Topical: Apply 1 drop to the back of the neck and 1 drop to the feet. Rub in the oil for 30 seconds to 1 minute. Each bottle has an orifice that allows the oil to be expelled drop by drop. Dilution is not required, except for the most sensitive skin. Apply in the morning. Aromatic Method: Diffuse one diffuser-full (8-12 drops of oil in water) at night.	Total n=26 Participants Total of all reporting groups
Age, Categorical <=18 years	12 Participants n=5 Participants	14 Participants n=7 Participants	26 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	12 Participants n=7 Participants	22 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=5 Participants	14 Participants n=7 Participants	26 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	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	10 Participants n=5 Participants	11 Participants n=7 Participants	21 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	2 Participants n=7 Participants	4 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	12 participants n=5 Participants	14 participants n=7 Participants	26 participants n=5 Participants
Children's Sleep Habits Questionnaire (CSHQ)	54.25 units on a scale 0 to 99 higher worse n=5 Participants	49.71 units on a scale 0 to 99 higher worse n=7 Participants	51.98 units on a scale 0 to 99 higher worse n=5 Participants
Parent-rated Anxiety Scale for Autism Spectrum Disorder (PRAS-ASD)	32.58 units on a scale 0 to 75 higher worse n=5 Participants	31.71 units on a scale 0 to 75 higher worse n=7 Participants	32.15 units on a scale 0 to 75 higher worse n=5 Participants

PRIMARY outcome

Timeframe: 28 Weeks

Population: Early terminations occurred throughout the study. Described in study flow table.

Outcome measures

Outcome measures
Measure	Subjects Received Re-Connect Then the Comparator Oil Blend n=12 Participants Subjects were randomized to order. Twelve subjects were randomized to Re-connect for the first 3-months, then after the one-month washout they received the coconut oil comparator during the last 3-months. The PedsQL was administered at screen, Visit 6 (at the end of the first treatment), and Visit 10 (the end of the second treatment)	Subjects Revieved the Comparator Oil Blend and Then Re-Connnec n=14 Participants Subjects were randomized to treatment order. Fourteen subjects received the comparator oil blend for the first 3-months, then after the one-month washout they received Re-connect (last 3-months).The PedsQL was administered at screen, Visit 6 (at the end of the first treatment), and Visit 10 (the end of the second treatment)
Pediatric Quality of Life Inventory Visit 6 Means	61.5 Total Score Standard Deviation 11.3	65.3 Total Score Standard Deviation 8.8
Pediatric Quality of Life Inventory Visit 10 Means	64.3 Total Score Standard Deviation 15.7	66.6 Total Score Standard Deviation 5.5
Pediatric Quality of Life Inventory Baseline Means	45.5 Total Score Standard Deviation 12.8	56.2 Total Score Standard Deviation 5.9

SECONDARY outcome

Timeframe: 28 Weeks

Population: Early terminations occurred through out the study. See the Study flow table.

Children's Sleep Habits Questionnaire (CSHQ) (Owens, Spirito, \& Mcguinn, 2000). The abbreviated CSHQ is a valid measure of sleep problems with good psychometric properties. It includes 33 items and is rated retrospectively over the previous week by parents to screen for the most common sleep problems. The Abbreviated CSHQ 33 items include eight key sleep domains. The eight subscales include: (1) bedtime resistance (2) sleep onset latency, (3) sleep duration, (4) anxiety around sleep, (5) night awakenings, (6) sleep disordered breathing, (7) parasomnias and (8) morning waking/daytime sleepiness. The 33 items are summed to get a total sleep disturbance score. A total sleep disturbance score of 41 or greater for the CSHQ's 33 items has been reported to be an appropriate clinical cut-off for identifying sleep disturbance in children. Responses range from 0 to 3 with a total range of 0 to 99 for all 33 items and higher scores indicate more sleep disturbance.

Outcome measures

Outcome measures
Measure	Subjects Received Re-Connect Then the Comparator Oil Blend n=12 Participants Subjects were randomized to order. Twelve subjects were randomized to Re-connect for the first 3-months, then after the one-month washout they received the coconut oil comparator during the last 3-months. The PedsQL was administered at screen, Visit 6 (at the end of the first treatment), and Visit 10 (the end of the second treatment)	Subjects Revieved the Comparator Oil Blend and Then Re-Connnec n=14 Participants Subjects were randomized to treatment order. Fourteen subjects received the comparator oil blend for the first 3-months, then after the one-month washout they received Re-connect (last 3-months).The PedsQL was administered at screen, Visit 6 (at the end of the first treatment), and Visit 10 (the end of the second treatment)
Children's Sleep Habits Questionnaire Baseline Means	54.3 Sleep Disturbance Total Score of 33 item Standard Deviation 7.9	49.7 Sleep Disturbance Total Score of 33 item Standard Deviation 11.1
Children's Sleep Habits Questionnaire Visit 6 Means	42.6 Sleep Disturbance Total Score of 33 item Standard Deviation 6.6	43.1 Sleep Disturbance Total Score of 33 item Standard Deviation 6.5
Children's Sleep Habits Questionnaire Visit 10 Means	43.0 Sleep Disturbance Total Score of 33 item Standard Deviation 6.7	44.5 Sleep Disturbance Total Score of 33 item Standard Deviation 7.0

SECONDARY outcome

Timeframe: 28 Weeks

Population: Early terminations occurred throughout the study. See the study flow table.

The PRAS-ASD (Scahill et al., 2019), is a parent-rated scale used to measure anxiety in children with autism spectrum disorder. The 25 items on the PRAS-ASD each range from 0 to 3 with a possible total of 75. Higher scores indication more anxiety.

Outcome measures

Outcome measures
Measure	Subjects Received Re-Connect Then the Comparator Oil Blend n=12 Participants Subjects were randomized to order. Twelve subjects were randomized to Re-connect for the first 3-months, then after the one-month washout they received the coconut oil comparator during the last 3-months. The PedsQL was administered at screen, Visit 6 (at the end of the first treatment), and Visit 10 (the end of the second treatment)	Subjects Revieved the Comparator Oil Blend and Then Re-Connnec n=14 Participants Subjects were randomized to treatment order. Fourteen subjects received the comparator oil blend for the first 3-months, then after the one-month washout they received Re-connect (last 3-months).The PedsQL was administered at screen, Visit 6 (at the end of the first treatment), and Visit 10 (the end of the second treatment)
Parent-rated Anxiety Scale for Autism Spectrum Disorder PRAS-ASD Baseline Means	32.6 Total Score Standard Deviation 15.45	31.7 Total Score Standard Deviation 10.1
Parent-rated Anxiety Scale for Autism Spectrum Disorder PRAS-ASD Visit 6 Means	12.6 Total Score Standard Deviation 11.9	26.4 Total Score Standard Deviation 14.6
Parent-rated Anxiety Scale for Autism Spectrum Disorder PRAS-ASD Visit 10 Means	7.9 Total Score Standard Deviation 5.4	24.0 Total Score Standard Deviation 13.8

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 Weeks

Population: Early terminations occurred throughout the study. See the study flow table.

Developmental Disabilities - Children's Global Assessment Scale (DD-CGAS) (Wagner et al., 2007). The clinician-rated DD-CGAS measures global functioning in children with developmental disorders in treatment studies. The DD-CGAS was used to characterize impairment in the following four domains: Self Care, Communication, Social Behavior, and School/Academic. In addition, this scale also includes a series of descriptive "bands" to characterize global functioning in children with pervasive developmental disorders from "extreme and pervasive impairment" through "superior functioning." Scores range fro 1 to 100 and higher scores on the DD-CGAS indicate increased independence of daily functioning.

Outcome measures

Outcome measures
Measure	Subjects Received Re-Connect Then the Comparator Oil Blend n=12 Participants Subjects were randomized to order. Twelve subjects were randomized to Re-connect for the first 3-months, then after the one-month washout they received the coconut oil comparator during the last 3-months. The PedsQL was administered at screen, Visit 6 (at the end of the first treatment), and Visit 10 (the end of the second treatment)	Subjects Revieved the Comparator Oil Blend and Then Re-Connnec n=14 Participants Subjects were randomized to treatment order. Fourteen subjects received the comparator oil blend for the first 3-months, then after the one-month washout they received Re-connect (last 3-months).The PedsQL was administered at screen, Visit 6 (at the end of the first treatment), and Visit 10 (the end of the second treatment)
Developmental Disabilities - Children's Global Assessment Scale (DD=CGAS) Baseline Means	54.8 Clinician Global Rating Standard Deviation 13.0	52.6 Clinician Global Rating Standard Deviation 12.7
Developmental Disabilities - Children's Global Assessment Scale (DD=CGAS) Visit 6 Means	57.9 Clinician Global Rating Standard Deviation 14.6	55.6 Clinician Global Rating Standard Deviation 13.5
Developmental Disabilities - Children's Global Assessment Scale (DD=CGAS) Visit 10 Means	57.4 Clinician Global Rating Standard Deviation 16.6	62.8 Clinician Global Rating Standard Deviation 8.8

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 Weeks

Adverse Events (AEs). To minimize the risk, subjects will be systematically monitored. AEs, vital signs, including resting BP, will be evaluated at each visit throughout all phases of the study. When the treating clinician elicits an AE, it will be documented on a case report form, regardless of suspected relationship to the essential oil. For all AEs, the investigator will obtain sufficient information to determine the onset, course, and outcome of the AE. If a subject has experienced an AE, the subject may return to the site for an unscheduled visit at the PI's discretion. If any of these AEs are serious and/or unexpected, the site PI will contact the Sponsor and notify the IRB as appropriate. Potential AEs include sun sensitivity due to the Bergamot in the essential oil, possibly gynecomastia in pre-pubescent males due to the lavender oil in the essential oil, and skin irritation at the application site.

Outcome measures

Outcome measures
Measure	Subjects Received Re-Connect Then the Comparator Oil Blend n=12 Participants Subjects were randomized to order. Twelve subjects were randomized to Re-connect for the first 3-months, then after the one-month washout they received the coconut oil comparator during the last 3-months. The PedsQL was administered at screen, Visit 6 (at the end of the first treatment), and Visit 10 (the end of the second treatment)	Subjects Revieved the Comparator Oil Blend and Then Re-Connnec n=14 Participants Subjects were randomized to treatment order. Fourteen subjects received the comparator oil blend for the first 3-months, then after the one-month washout they received Re-connect (last 3-months).The PedsQL was administered at screen, Visit 6 (at the end of the first treatment), and Visit 10 (the end of the second treatment)
Adverse Events Visit 6	27 total number of events per condition	35 total number of events per condition
Adverse Events Visit 10	34 total number of events per condition	18 total number of events per condition

Adverse Events

Reconnect

Serious events: 0 serious events

Other events: 24 other events

Deaths: 0 deaths

Coconut Oil Blend (Comparator)

Serious events: 0 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Dr. Jill Ann Hollway

The Ohio State University Nisonger Center

Phone: 614-688-3848

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Reconnect n=24 participants at risk Subjects were randomized to treatment order in a cross-over study design. The adverse events noted below were recorded from subjects in the Reconnect group.	Coconut Oil Blend (Comparator) n=23 participants at risk Subjects were randomized to treatment order in a cross-over study design. The adverse events noted below were recorded from subjects in the coconut oil comparator group.
Gastrointestinal disorders Vomiting	12.5% 3/24 • Number of events 3 • Participants are systematically monitored for adverse events by study physicians (at all 10 visits). Vital signs, including resting BP, were evaluated at every visit as well. According to all laboratory reports and physician review of adverse events potentially related to oil blend administration, there are no clinically significant abnormal values or adverse events. Recorded adverse events related to study treatment include minor events such as hyperactivity and intolerance to oil smell	26.1% 6/23 • Number of events 6 • Participants are systematically monitored for adverse events by study physicians (at all 10 visits). Vital signs, including resting BP, were evaluated at every visit as well. According to all laboratory reports and physician review of adverse events potentially related to oil blend administration, there are no clinically significant abnormal values or adverse events. Recorded adverse events related to study treatment include minor events such as hyperactivity and intolerance to oil smell
Respiratory, thoracic and mediastinal disorders URI	20.8% 5/24 • Number of events 5 • Participants are systematically monitored for adverse events by study physicians (at all 10 visits). Vital signs, including resting BP, were evaluated at every visit as well. According to all laboratory reports and physician review of adverse events potentially related to oil blend administration, there are no clinically significant abnormal values or adverse events. Recorded adverse events related to study treatment include minor events such as hyperactivity and intolerance to oil smell	21.7% 5/23 • Number of events 5 • Participants are systematically monitored for adverse events by study physicians (at all 10 visits). Vital signs, including resting BP, were evaluated at every visit as well. According to all laboratory reports and physician review of adverse events potentially related to oil blend administration, there are no clinically significant abnormal values or adverse events. Recorded adverse events related to study treatment include minor events such as hyperactivity and intolerance to oil smell
Psychiatric disorders Increased Irritability	16.7% 4/24 • Number of events 4 • Participants are systematically monitored for adverse events by study physicians (at all 10 visits). Vital signs, including resting BP, were evaluated at every visit as well. According to all laboratory reports and physician review of adverse events potentially related to oil blend administration, there are no clinically significant abnormal values or adverse events. Recorded adverse events related to study treatment include minor events such as hyperactivity and intolerance to oil smell	4.3% 1/23 • Number of events 1 • Participants are systematically monitored for adverse events by study physicians (at all 10 visits). Vital signs, including resting BP, were evaluated at every visit as well. According to all laboratory reports and physician review of adverse events potentially related to oil blend administration, there are no clinically significant abnormal values or adverse events. Recorded adverse events related to study treatment include minor events such as hyperactivity and intolerance to oil smell
Infections and infestations Streptococcal pharyngitis,	12.5% 3/24 • Number of events 3 • Participants are systematically monitored for adverse events by study physicians (at all 10 visits). Vital signs, including resting BP, were evaluated at every visit as well. According to all laboratory reports and physician review of adverse events potentially related to oil blend administration, there are no clinically significant abnormal values or adverse events. Recorded adverse events related to study treatment include minor events such as hyperactivity and intolerance to oil smell	4.3% 1/23 • Number of events 1 • Participants are systematically monitored for adverse events by study physicians (at all 10 visits). Vital signs, including resting BP, were evaluated at every visit as well. According to all laboratory reports and physician review of adverse events potentially related to oil blend administration, there are no clinically significant abnormal values or adverse events. Recorded adverse events related to study treatment include minor events such as hyperactivity and intolerance to oil smell
Renal and urinary disorders Enuresis	8.3% 2/24 • Number of events 2 • Participants are systematically monitored for adverse events by study physicians (at all 10 visits). Vital signs, including resting BP, were evaluated at every visit as well. According to all laboratory reports and physician review of adverse events potentially related to oil blend administration, there are no clinically significant abnormal values or adverse events. Recorded adverse events related to study treatment include minor events such as hyperactivity and intolerance to oil smell	8.7% 2/23 • Number of events 2 • Participants are systematically monitored for adverse events by study physicians (at all 10 visits). Vital signs, including resting BP, were evaluated at every visit as well. According to all laboratory reports and physician review of adverse events potentially related to oil blend administration, there are no clinically significant abnormal values or adverse events. Recorded adverse events related to study treatment include minor events such as hyperactivity and intolerance to oil smell
Immune system disorders Environmental Allergy	8.3% 2/24 • Number of events 2 • Participants are systematically monitored for adverse events by study physicians (at all 10 visits). Vital signs, including resting BP, were evaluated at every visit as well. According to all laboratory reports and physician review of adverse events potentially related to oil blend administration, there are no clinically significant abnormal values or adverse events. Recorded adverse events related to study treatment include minor events such as hyperactivity and intolerance to oil smell	13.0% 3/23 • Number of events 3 • Participants are systematically monitored for adverse events by study physicians (at all 10 visits). Vital signs, including resting BP, were evaluated at every visit as well. According to all laboratory reports and physician review of adverse events potentially related to oil blend administration, there are no clinically significant abnormal values or adverse events. Recorded adverse events related to study treatment include minor events such as hyperactivity and intolerance to oil smell
Respiratory, thoracic and mediastinal disorders Tussis	4.2% 1/24 • Number of events 1 • Participants are systematically monitored for adverse events by study physicians (at all 10 visits). Vital signs, including resting BP, were evaluated at every visit as well. According to all laboratory reports and physician review of adverse events potentially related to oil blend administration, there are no clinically significant abnormal values or adverse events. Recorded adverse events related to study treatment include minor events such as hyperactivity and intolerance to oil smell	17.4% 4/23 • Number of events 4 • Participants are systematically monitored for adverse events by study physicians (at all 10 visits). Vital signs, including resting BP, were evaluated at every visit as well. According to all laboratory reports and physician review of adverse events potentially related to oil blend administration, there are no clinically significant abnormal values or adverse events. Recorded adverse events related to study treatment include minor events such as hyperactivity and intolerance to oil smell
Infections and infestations Fever	8.3% 2/24 • Number of events 2 • Participants are systematically monitored for adverse events by study physicians (at all 10 visits). Vital signs, including resting BP, were evaluated at every visit as well. According to all laboratory reports and physician review of adverse events potentially related to oil blend administration, there are no clinically significant abnormal values or adverse events. Recorded adverse events related to study treatment include minor events such as hyperactivity and intolerance to oil smell	8.7% 2/23 • Number of events 2 • Participants are systematically monitored for adverse events by study physicians (at all 10 visits). Vital signs, including resting BP, were evaluated at every visit as well. According to all laboratory reports and physician review of adverse events potentially related to oil blend administration, there are no clinically significant abnormal values or adverse events. Recorded adverse events related to study treatment include minor events such as hyperactivity and intolerance to oil smell
Gastrointestinal disorders Gastroenteritis	0.00% 0/24 • Participants are systematically monitored for adverse events by study physicians (at all 10 visits). Vital signs, including resting BP, were evaluated at every visit as well. According to all laboratory reports and physician review of adverse events potentially related to oil blend administration, there are no clinically significant abnormal values or adverse events. Recorded adverse events related to study treatment include minor events such as hyperactivity and intolerance to oil smell	13.0% 3/23 • Number of events 3 • Participants are systematically monitored for adverse events by study physicians (at all 10 visits). Vital signs, including resting BP, were evaluated at every visit as well. According to all laboratory reports and physician review of adverse events potentially related to oil blend administration, there are no clinically significant abnormal values or adverse events. Recorded adverse events related to study treatment include minor events such as hyperactivity and intolerance to oil smell
Gastrointestinal disorders Gastrointestinal upset	8.3% 2/24 • Number of events 2 • Participants are systematically monitored for adverse events by study physicians (at all 10 visits). Vital signs, including resting BP, were evaluated at every visit as well. According to all laboratory reports and physician review of adverse events potentially related to oil blend administration, there are no clinically significant abnormal values or adverse events. Recorded adverse events related to study treatment include minor events such as hyperactivity and intolerance to oil smell	0.00% 0/23 • Participants are systematically monitored for adverse events by study physicians (at all 10 visits). Vital signs, including resting BP, were evaluated at every visit as well. According to all laboratory reports and physician review of adverse events potentially related to oil blend administration, there are no clinically significant abnormal values or adverse events. Recorded adverse events related to study treatment include minor events such as hyperactivity and intolerance to oil smell
Psychiatric disorders Increased Self Injury	4.2% 1/24 • Number of events 1 • Participants are systematically monitored for adverse events by study physicians (at all 10 visits). Vital signs, including resting BP, were evaluated at every visit as well. According to all laboratory reports and physician review of adverse events potentially related to oil blend administration, there are no clinically significant abnormal values or adverse events. Recorded adverse events related to study treatment include minor events such as hyperactivity and intolerance to oil smell	8.7% 2/23 • Number of events 2 • Participants are systematically monitored for adverse events by study physicians (at all 10 visits). Vital signs, including resting BP, were evaluated at every visit as well. According to all laboratory reports and physician review of adverse events potentially related to oil blend administration, there are no clinically significant abnormal values or adverse events. Recorded adverse events related to study treatment include minor events such as hyperactivity and intolerance to oil smell
Ear and labyrinth disorders Otitis media	0.00% 0/24 • Participants are systematically monitored for adverse events by study physicians (at all 10 visits). Vital signs, including resting BP, were evaluated at every visit as well. According to all laboratory reports and physician review of adverse events potentially related to oil blend administration, there are no clinically significant abnormal values or adverse events. Recorded adverse events related to study treatment include minor events such as hyperactivity and intolerance to oil smell	8.7% 2/23 • Number of events 2 • Participants are systematically monitored for adverse events by study physicians (at all 10 visits). Vital signs, including resting BP, were evaluated at every visit as well. According to all laboratory reports and physician review of adverse events potentially related to oil blend administration, there are no clinically significant abnormal values or adverse events. Recorded adverse events related to study treatment include minor events such as hyperactivity and intolerance to oil smell
Respiratory, thoracic and mediastinal disorders Rhinorrhea	8.3% 2/24 • Number of events 2 • Participants are systematically monitored for adverse events by study physicians (at all 10 visits). Vital signs, including resting BP, were evaluated at every visit as well. According to all laboratory reports and physician review of adverse events potentially related to oil blend administration, there are no clinically significant abnormal values or adverse events. Recorded adverse events related to study treatment include minor events such as hyperactivity and intolerance to oil smell	8.7% 2/23 • Number of events 2 • Participants are systematically monitored for adverse events by study physicians (at all 10 visits). Vital signs, including resting BP, were evaluated at every visit as well. According to all laboratory reports and physician review of adverse events potentially related to oil blend administration, there are no clinically significant abnormal values or adverse events. Recorded adverse events related to study treatment include minor events such as hyperactivity and intolerance to oil smell
Psychiatric disorders Sleep disturbance	0.00% 0/24 • Participants are systematically monitored for adverse events by study physicians (at all 10 visits). Vital signs, including resting BP, were evaluated at every visit as well. According to all laboratory reports and physician review of adverse events potentially related to oil blend administration, there are no clinically significant abnormal values or adverse events. Recorded adverse events related to study treatment include minor events such as hyperactivity and intolerance to oil smell	8.7% 2/23 • Number of events 2 • Participants are systematically monitored for adverse events by study physicians (at all 10 visits). Vital signs, including resting BP, were evaluated at every visit as well. According to all laboratory reports and physician review of adverse events potentially related to oil blend administration, there are no clinically significant abnormal values or adverse events. Recorded adverse events related to study treatment include minor events such as hyperactivity and intolerance to oil smell
Skin and subcutaneous tissue disorders Viral exanthem	8.3% 2/24 • Number of events 2 • Participants are systematically monitored for adverse events by study physicians (at all 10 visits). Vital signs, including resting BP, were evaluated at every visit as well. According to all laboratory reports and physician review of adverse events potentially related to oil blend administration, there are no clinically significant abnormal values or adverse events. Recorded adverse events related to study treatment include minor events such as hyperactivity and intolerance to oil smell	0.00% 0/23 • Participants are systematically monitored for adverse events by study physicians (at all 10 visits). Vital signs, including resting BP, were evaluated at every visit as well. According to all laboratory reports and physician review of adverse events potentially related to oil blend administration, there are no clinically significant abnormal values or adverse events. Recorded adverse events related to study treatment include minor events such as hyperactivity and intolerance to oil smell
Psychiatric disorders Increase of verbal stemming	0.00% 0/24 • Participants are systematically monitored for adverse events by study physicians (at all 10 visits). Vital signs, including resting BP, were evaluated at every visit as well. According to all laboratory reports and physician review of adverse events potentially related to oil blend administration, there are no clinically significant abnormal values or adverse events. Recorded adverse events related to study treatment include minor events such as hyperactivity and intolerance to oil smell	13.0% 3/23 • Number of events 3 • Participants are systematically monitored for adverse events by study physicians (at all 10 visits). Vital signs, including resting BP, were evaluated at every visit as well. According to all laboratory reports and physician review of adverse events potentially related to oil blend administration, there are no clinically significant abnormal values or adverse events. Recorded adverse events related to study treatment include minor events such as hyperactivity and intolerance to oil smell
Respiratory, thoracic and mediastinal disorders Adverse reaction to noxious oil smell	8.3% 2/24 • Number of events 2 • Participants are systematically monitored for adverse events by study physicians (at all 10 visits). Vital signs, including resting BP, were evaluated at every visit as well. According to all laboratory reports and physician review of adverse events potentially related to oil blend administration, there are no clinically significant abnormal values or adverse events. Recorded adverse events related to study treatment include minor events such as hyperactivity and intolerance to oil smell	0.00% 0/23 • Participants are systematically monitored for adverse events by study physicians (at all 10 visits). Vital signs, including resting BP, were evaluated at every visit as well. According to all laboratory reports and physician review of adverse events potentially related to oil blend administration, there are no clinically significant abnormal values or adverse events. Recorded adverse events related to study treatment include minor events such as hyperactivity and intolerance to oil smell