Anxiety, Autism Spectrum Disorder, Quality of Life, Sleep
Conditions
Keywords
Relaxation
Brief summary
Essential oils (aromatic oils extracted from plant parts) are routinely used by the public and are available on the market. Investigators are conducting this study because it is unknown whether the essential oils formulations will be safe and effective for improving quality of life in children with Autism Spectrum Disorder (ASD) by helping them relax and sleep. Children invited to participate in this study must be between 3-9 years of age and have been diagnosed with Autism Spectrum Disorder. Twenty eight children and their families will be enrolled in the study. Participants will try two different fragrant oils in a double-blind randomized order. Each child will receive each treatment for 3 months, with a 1-month washout period in between during which no oil is used.
Detailed description
The purpose of the study is to evaluate the use of two fragrant oil formulations to enhance quality of life by increasing relaxation and sleep quality in children with Autism Spectrum Disorder (ASD). Essential oils (aromatic oils extracted from plant parts) are routinely used by the public and are available on the market. Investigators are conducting this study because it is unknown whether the essential oils formulations will be safe and effective for helping children with ASD relax and sleep. To participate in this study children must be between 3-9 years of age and have been diagnosed with Autism Spectrum Disorder. Approximately 40 children will be screened to enroll 28 children and their families in the study. In a double-blind crossover study, participants will be randomized to treatment order. All participants will receive both fragrant oil blends. Those randomized will receive one fragrant oil blend for 3 months, with a 1-month washout period in between and then start the second fragrant oil blend in the last 3 months. The treatment orders are A/C and C/A. Study participation will last for 7 months. There will be one screening visit (about 5 hours long, which can be split into 2 visits), two baseline visits (about 2 hours each), two endpoint visits (2 hours each) and 5 other clinic visits (each 45-60 minutes). Visits will take place at the OSU Nisonger Center and the OSU General Clinical Research Center.
Interventions
BIOLOGICALReconnect
Topical Essential Oils mixture and aromatic method
BIOLOGICALCoconut oil Comparator
Topical Essential Oils mixture and aromatic method
Sponsors
Young Living Essential Oils
Jill Hollway
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
3 Years to 9 Years
Healthy volunteers
Yes
Inclusion criteria
* Outpatients between 3 and 9 years of age, inclusive; * Diagnosis of Autism Spectrum Disorder (ASD) by DSM-V; * Mean item score of \> or = 1.5 PedsQL Inventory; * Care provider who can reliably bring subject to clinic visits and provide trustworthy ratings.
Exclusion criteria
* Bipolar disorder by Child & Adolescent Symptom Inventory (CASI, Gadow & Sprafkin, 1997) and clinical interview/history, or major depression accompanied by family history of bipolar disorder; * Children with allergies to essential oils; * Children with seizure disorder/epilepsy; * Significant physical illness (e.g., serious cardiovascular, liver or renal pathology); * Medications specifically given for insomnia and exogenous melatonin, which have the potential to confound study results, within the previous 2 weeks before baseline; * Anticipated changes of doses of medication or other medical treatments or supplements; * Weight less than 10 kg; * Sleep Disordered Breathing (SDB) as defined by a total score of \> or = 3 on the CSHQ SDB subscale and parent report; * Nut allergies; * Allergy to vanilla; * A substantial trial of essential oil use within the past 6 months (i.e., consistent use for 6 weeks).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pediatric Quality of Life Inventory | 28 Weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Children's Sleep Habits Questionnaire | 28 Weeks | 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. |
| Parent-rated Anxiety Scale for Autism Spectrum Disorder PRAS-ASD | 28 Weeks | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Developmental Disabilities - Children's Global Assessment Scale (DD=CGAS) | 28 Weeks | 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. |
| Adverse Events | 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. |
Countries
United States
Participant flow
Recruitment details
Forty subjects were screened for eligibility between between July 22nd 2015 and June 22nd 2017, at the Ohio State University's Nisonger Center.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| A/C (Reconnect/Comparator) 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. | 12 |
| C/A (Comparator/Reconnect) 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. | 14 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Family | 1 | 2 |
| Overall Study | Increased Irritability | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Negative Behavior | 1 | 0 |
| Overall Study | Unpalatable Fragrance | 2 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | A/C (Reconnect/Comparator) | C/A (Comparator/Reconnect) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 12 Participants | 14 Participants | 26 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Children's Sleep Habits Questionnaire (CSHQ) | 54.25 units on a scale 0 to 99 higher worse | 49.71 units on a scale 0 to 99 higher worse | 51.98 units on a scale 0 to 99 higher worse |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 14 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Parent-rated Anxiety Scale for Autism Spectrum Disorder (PRAS-ASD) | 32.58 units on a scale 0 to 75 higher worse | 31.71 units on a scale 0 to 75 higher worse | 32.15 units on a scale 0 to 75 higher worse |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 11 Participants | 21 Participants |
| Region of Enrollment United States | 12 participants | 14 participants | 26 participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 10 Participants | 12 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 23 |
| other Total, other adverse events | 24 / 24 | 23 / 23 |
| serious Total, serious adverse events | 0 / 24 | 0 / 23 |
Outcome results
Primary
Pediatric Quality of Life Inventory
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.
Time frame: 28 Weeks
Population: Early terminations occurred throughout the study. Described in study flow table.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Subjects Received Re-Connect Then the Comparator Oil Blend | Pediatric Quality of Life Inventory | Baseline Means | 45.5 Total Score | Standard Deviation 12.8 |
| Subjects Received Re-Connect Then the Comparator Oil Blend | Pediatric Quality of Life Inventory | Visit 6 Means | 61.5 Total Score | Standard Deviation 11.3 |
| Subjects Received Re-Connect Then the Comparator Oil Blend | Pediatric Quality of Life Inventory | Visit 10 Means | 64.3 Total Score | Standard Deviation 15.7 |
| Subjects Revieved the Comparator Oil Blend and Then Re-Connnec | Pediatric Quality of Life Inventory | Baseline Means | 56.2 Total Score | Standard Deviation 5.9 |
| Subjects Revieved the Comparator Oil Blend and Then Re-Connnec | Pediatric Quality of Life Inventory | Visit 6 Means | 65.3 Total Score | Standard Deviation 8.8 |
| Subjects Revieved the Comparator Oil Blend and Then Re-Connnec | Pediatric Quality of Life Inventory | Visit 10 Means | 66.6 Total Score | Standard Deviation 5.5 |
Secondary
Children's Sleep Habits Questionnaire
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.
Time frame: 28 Weeks
Population: Early terminations occurred through out the study. See the Study flow table.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Subjects Received Re-Connect Then the Comparator Oil Blend | Children's Sleep Habits Questionnaire | Baseline Means | 54.3 Sleep Disturbance Total Score of 33 item | Standard Deviation 7.9 |
| Subjects Received Re-Connect Then the Comparator Oil Blend | Children's Sleep Habits Questionnaire | Visit 6 Means | 42.6 Sleep Disturbance Total Score of 33 item | Standard Deviation 6.6 |
| Subjects Received Re-Connect Then the Comparator Oil Blend | Children's Sleep Habits Questionnaire | Visit 10 Means | 43.0 Sleep Disturbance Total Score of 33 item | Standard Deviation 6.7 |
| Subjects Revieved the Comparator Oil Blend and Then Re-Connnec | Children's Sleep Habits Questionnaire | Baseline Means | 49.7 Sleep Disturbance Total Score of 33 item | Standard Deviation 11.1 |
| Subjects Revieved the Comparator Oil Blend and Then Re-Connnec | Children's Sleep Habits Questionnaire | Visit 6 Means | 43.1 Sleep Disturbance Total Score of 33 item | Standard Deviation 6.5 |
| Subjects Revieved the Comparator Oil Blend and Then Re-Connnec | Children's Sleep Habits Questionnaire | Visit 10 Means | 44.5 Sleep Disturbance Total Score of 33 item | Standard Deviation 7 |
Secondary
Parent-rated Anxiety Scale for Autism Spectrum Disorder PRAS-ASD
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.
Time frame: 28 Weeks
Population: Early terminations occurred throughout the study. See the study flow table.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Subjects Received Re-Connect Then the Comparator Oil Blend | Parent-rated Anxiety Scale for Autism Spectrum Disorder PRAS-ASD | Visit 6 Means | 12.6 Total Score | Standard Deviation 11.9 |
| Subjects Received Re-Connect Then the Comparator Oil Blend | Parent-rated Anxiety Scale for Autism Spectrum Disorder PRAS-ASD | Baseline Means | 32.6 Total Score | Standard Deviation 15.45 |
| Subjects Received Re-Connect Then the Comparator Oil Blend | Parent-rated Anxiety Scale for Autism Spectrum Disorder PRAS-ASD | Visit 10 Means | 7.9 Total Score | Standard Deviation 5.4 |
| Subjects Revieved the Comparator Oil Blend and Then Re-Connnec | Parent-rated Anxiety Scale for Autism Spectrum Disorder PRAS-ASD | Baseline Means | 31.7 Total Score | Standard Deviation 10.1 |
| Subjects Revieved the Comparator Oil Blend and Then Re-Connnec | Parent-rated Anxiety Scale for Autism Spectrum Disorder PRAS-ASD | Visit 6 Means | 26.4 Total Score | Standard Deviation 14.6 |
| Subjects Revieved the Comparator Oil Blend and Then Re-Connnec | Parent-rated Anxiety Scale for Autism Spectrum Disorder PRAS-ASD | Visit 10 Means | 24.0 Total Score | Standard Deviation 13.8 |
Other Pre-specified
Adverse Events
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.
Time frame: 28 Weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Subjects Received Re-Connect Then the Comparator Oil Blend | Adverse Events | Visit 6 | 27 total number of events per condition |
| Subjects Received Re-Connect Then the Comparator Oil Blend | Adverse Events | Visit 10 | 34 total number of events per condition |
| Subjects Revieved the Comparator Oil Blend and Then Re-Connnec | Adverse Events | Visit 6 | 35 total number of events per condition |
| Subjects Revieved the Comparator Oil Blend and Then Re-Connnec | Adverse Events | Visit 10 | 18 total number of events per condition |
Other Pre-specified
Developmental Disabilities - Children's Global Assessment Scale (DD=CGAS)
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.
Time frame: 28 Weeks
Population: Early terminations occurred throughout the study. See the study flow table.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Subjects Received Re-Connect Then the Comparator Oil Blend | Developmental Disabilities - Children's Global Assessment Scale (DD=CGAS) | Baseline Means | 54.8 Clinician Global Rating | Standard Deviation 13 |
| Subjects Received Re-Connect Then the Comparator Oil Blend | Developmental Disabilities - Children's Global Assessment Scale (DD=CGAS) | Visit 6 Means | 57.9 Clinician Global Rating | Standard Deviation 14.6 |
| Subjects Received Re-Connect Then the Comparator Oil Blend | Developmental Disabilities - Children's Global Assessment Scale (DD=CGAS) | Visit 10 Means | 57.4 Clinician Global Rating | Standard Deviation 16.6 |
| Subjects Revieved the Comparator Oil Blend and Then Re-Connnec | Developmental Disabilities - Children's Global Assessment Scale (DD=CGAS) | Baseline Means | 52.6 Clinician Global Rating | Standard Deviation 12.7 |
| Subjects Revieved the Comparator Oil Blend and Then Re-Connnec | Developmental Disabilities - Children's Global Assessment Scale (DD=CGAS) | Visit 6 Means | 55.6 Clinician Global Rating | Standard Deviation 13.5 |
| Subjects Revieved the Comparator Oil Blend and Then Re-Connnec | Developmental Disabilities - Children's Global Assessment Scale (DD=CGAS) | Visit 10 Means | 62.8 Clinician Global Rating | Standard Deviation 8.8 |