Autism, Autism Spectrum Disorder, Non-verbal Learning Disorder
Conditions
Keywords
autism, learning disorder, natural supplements, NAC, omega-3
Brief summary
This study consists of a 6-week, open-label, randomized clinical trial study to compare efficacy and tolerability of the natural treatments omega-3 fatty acids, inositol, and N-acetylcysteine (NAC) in the treatment of mood dysregulation in children and adolescents with non-verbal learning disability (NVLD) or Autism Spectrum Disorder (ASD). Subjects will include youth ages 5-17 years with a non-verbal learning disability (NVLD) or autism spectrum disorder (ASD) and current symptoms of emotional dysregulation.
Interventions
Open-label Treatment with Omega-3 Fatty Acids + Inositol
Open-label Treatment with acetylcysteine
Sponsors
Demarest Lloyd Jr. Foundation
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
5 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* A previous established diagnosis of non-verbal learning disability (NVLD) or DSM-V Autism Spectrum Disorder and/ or combined T-scores on the Child Behavior Checklist \> 195 on the Withdrawn + Social Problems + Thought Problems subscales. * Current symptoms of emotional dysregulation as indicated by combined T-scores on the Child Behavior Checklist \> 180 on the Anxiety/Depression + Aggression + Attention subscales. * Subjects and their caregivers must be English-speaking and have a level of understanding sufficient to communicate intelligently with the investigator and study coordinator, and to cooperate with all tests and examinations required by the protocol. * Subjects and their caregivers must be willing and able to comply with all study procedures. * Each subject and his/her authorized legal representative must understand the nature of the study. The subject's authorized legal representative must sign an informed consent document and the subject must sign an informed assent document. * Subject must be able to swallow pills. * Subject must have access to a computer with a camera, speaker, microphone, and internet connection.
Exclusion criteria
* Investigator and his/her immediate family; defined as the investigator's spouse, parent, child, grandparent, or grandchild. * Serious or unstable illness including hepatic, renal, gastroenterological, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease. * History of bleeding diathesis, including those with von Willebrand disease. * Uncorrected hypothyroidism or hyperthyroidism. * History of sensitivity to omega-3 fatty acids, inositol or NAC. A non-responder or history of intolerance to omega-3 fatty acid, inositol or NAC after 2 months of treatment at adequate doses as determined by the clinician. * Severe allergies or multiple adverse drug reactions. * Unstable or untreated seizure disorder. * DSM-IV substance use, abuse or dependence. * Judged clinically to be at serious suicidal risk for C-SSRS score ≥ 4. * Current diagnosis of schizophrenia. * Current diagnosis or symptoms of psychosis. * IQ \< 70. * Pregnant or nursing. * Weighs less than 12.5kg.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in the Parent-Young Mania Rating Scale (P-YMRS) Score | Baseline to 6 Weeks | The YMRS consists of 11 items rated on a scale from 0 (symptoms not present) to 4 (symptoms extremely severe). It is used to assess manic symptoms. The YMRS score ranges from 0-60. Questions are asked about the last week. This scale is generally accepted as the main outcome measure in studies of pediatric bipolar disorder and is linked directly to the core symptoms of mania. Higher scores indicate more severe manic symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in the Parent-completed Children's Depression Inventory (CDI) | Baseline to 6 Weeks | The CDI consists of 27 items quantifying symptoms such as depressed mood, hedonic capacity, vegetative functions, self-evaluation, and interpersonal behaviors. Each item consists of three statements graded in order of increasing severity from 0 to 2; parents select the one that characterized their child's symptoms best during the past 1 week. The item scores are combined into a total depression score, which ranges from 0 to 54. A higher CDI score means a higher depressive state. |
| Mean Change in the NIMH Clinical Global Improvement Scale (CGI) | Baseline to 6 Weeks | The CGI-BPD-S is a clinician-rated measure of bipolar disorder severity. Severity scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). The outcome reported reflects the change from baseline in CGI-BPD-S scores and negative scores represent improvement (i.e., decrease in severity from baseline). |
Countries
United States
Participant flow
Recruitment details
We will use advertisements on the Internet, including advertisements posted on the Partners Clinical trials website, and flyers to recruit participants. Individuals who respond to advertising will go through a phone screen with the study coordinator or research assistant via phone and will then be screened by a study clinician.
Pre-assignment details
Participants may also be recruited from the referral pool of existing and new patients in the Pediatric Psychopharmacology Program and the MGH Child Psychiatry Outpatient Clinic or from the pool of children screened for participation in Protocol #2019-P-000846 (An Open-Label Clinical Trial Conducted via Telepsychiatry of Complementary and Alternative Treatments (Omega-3 Fatty Acids and Inositol vs. N-acetylcysteine) for the Management of Emotional Dysregulation in Youth).
Participants by arm
| Arm | Count |
|---|---|
| Omega-3 Fatty Acid Plus Inositol Subjects randomized to receive omega-3 fatty acids plus inositol received 2040mg (6 340mg capsules) of omega-3 fatty acids for the duration of the study. Subjects weighing 25kg or more also received 2000mg (2 1000mg capsules) of inositol per day. Children weighing less than 25kg received 1000mg (1 1000mg capsule) of inositol per day | 27 |
| N-Acetylcysteine Subjects randomized to receive NAC received NAC in either an effervescent tablet (PharmaNAC brand was chosen due to its palatability and ease of administration) or could instead opt for NAC encapsulated. For those who chose to take NAC in the effervescent tablet form, subjects age 12 and under received 1800mg daily (2 900 mg tablets) NAC and subjects age 13-17 received NAC 2700mg (3 900mg tablets) daily. For those who chose to take NAC in the capsule form, subjects age 12 and under received 1800mg (3 600mg capsules) of NAC daily and subjects age 13-17 received 2400mg (4 600mg capsules) of NAC daily. | 27 |
| Total | 54 |
Baseline characteristics
| Characteristic | Omega-3 Fatty Acid Plus Inositol | N-Acetylcysteine | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 27 Participants | 27 Participants | 54 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 2 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants | 24 Participants | 43 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 4 Participants | 7 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 | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 21 Participants | 20 Participants | 41 Participants |
| Sex: Female, Male Female | 10 Participants | 6 Participants | 16 Participants |
| Sex: Female, Male Male | 17 Participants | 21 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 27 | 0 / 27 |
| other Total, other adverse events | 11 / 27 | 13 / 27 |
| serious Total, serious adverse events | 0 / 27 | 1 / 27 |
Outcome results
Primary
Mean Change in the Parent-Young Mania Rating Scale (P-YMRS) Score
The YMRS consists of 11 items rated on a scale from 0 (symptoms not present) to 4 (symptoms extremely severe). It is used to assess manic symptoms. The YMRS score ranges from 0-60. Questions are asked about the last week. This scale is generally accepted as the main outcome measure in studies of pediatric bipolar disorder and is linked directly to the core symptoms of mania. Higher scores indicate more severe manic symptoms.
Time frame: Baseline to 6 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Omega-3 Fatty Acid Plus Inositol | Mean Change in the Parent-Young Mania Rating Scale (P-YMRS) Score | 0.0 Units on a Scale | Standard Deviation 7.9 |
| N-Acetylcysteine | Mean Change in the Parent-Young Mania Rating Scale (P-YMRS) Score | -2.6 Units on a Scale | Standard Deviation 8.1 |
Secondary
Mean Change in the NIMH Clinical Global Improvement Scale (CGI)
The CGI-BPD-S is a clinician-rated measure of bipolar disorder severity. Severity scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). The outcome reported reflects the change from baseline in CGI-BPD-S scores and negative scores represent improvement (i.e., decrease in severity from baseline).
Time frame: Baseline to 6 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Omega-3 Fatty Acid Plus Inositol | Mean Change in the NIMH Clinical Global Improvement Scale (CGI) | -1.1 Units on a Scale | Standard Deviation 1.3 |
| N-Acetylcysteine | Mean Change in the NIMH Clinical Global Improvement Scale (CGI) | -0.7 Units on a Scale | Standard Deviation 1.1 |
Secondary
Mean Change in the Parent-completed Children's Depression Inventory (CDI)
The CDI consists of 27 items quantifying symptoms such as depressed mood, hedonic capacity, vegetative functions, self-evaluation, and interpersonal behaviors. Each item consists of three statements graded in order of increasing severity from 0 to 2; parents select the one that characterized their child's symptoms best during the past 1 week. The item scores are combined into a total depression score, which ranges from 0 to 54. A higher CDI score means a higher depressive state.
Time frame: Baseline to 6 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Omega-3 Fatty Acid Plus Inositol | Mean Change in the Parent-completed Children's Depression Inventory (CDI) | -3.4 Units on a Scale | Standard Deviation 7.7 |
| N-Acetylcysteine | Mean Change in the Parent-completed Children's Depression Inventory (CDI) | -1.3 Units on a Scale | Standard Deviation 6.5 |