Autism
Conditions
Keywords
Adults
Brief summary
Primary: Demonstrate reduced frequency and intensity of maladaptive behaviors as measured by the Aberrant Behavior Checklist (ABC) Irritability subscale in subjects given Nuedexta 8 weeks over subjects given placebo. Secondary: Demonstrate a trend towards reduced aggressive behavior as measured by Overt Aggression Scale (OAS).
Detailed description
This is a randomized placebo-controlled crossover study. The parents, neuropsychologists, clinical research coordinator (CRC) and PI will be blinded as to whether subjects are on placebo or Nuedexta. Nuedexta will be given once daily for 7 days. If well-tolerated, it will be given every 12 hours for the next 7 weeks. Patients may also remain on the once-daily dose if desired. The study will last 44 weeks. This includes 20 weeks for study enrollment, 8 weeks of treatment/placebo, 4 weeks for washout, and a second 8 week-period of treatment/placebo followed by 4 weeks of washout. Subjects will be randomized to 8 weeks of Nuedexta/placebo. After the 8 week follow-up visit, there will be a 4 week washout period. At week 12 (second baseline), the groups will crossover for another 8 weeks of Nuedexta/placebo. Study endpoints will be measured in the both groups at weeks 8, 12, and 20. A final study visit will occur at week 24.
Interventions
DRUGNuedexta
Nuedexta (Dextromethorphan hydrobromide 20 mg and quinidine sulfate 10 mg) will be given once daily for 7 days. If well-tolerated, it will be given every 12 hours for the next 7 weeks.
OTHERPlacebo
Placebo will be given once daily for 7 days.
Sponsors
Sutter Health
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. 18 to 60 years of age 2. Have a collateral informant who can attend visit and answer questionnaires pertaining to participant behavior 3. Diagnosis of autistic spectrum disorder based on the Diagnostic and Statistical Manual, 4th edition, Text Revised (DSM-IV-TR) criteria, developmental history, and Autism Diagnostic Observation Schedule (ADOS); or confirmed diagnosis of autism during childhood through similar methods 4. Capable of giving informed consent, or have a legal guardian capable of giving consent on the subject's behalf; patient able to assent to participate 5. Mood issues and frontal lobe type perseveration issues 6. No medication changes within 30 days and no use of new medications during the course of the study except for non-related conditions approved by the investigators
Exclusion criteria
1. Clinically uncontrolled epilepsy 2. Cardiovascular conditions including cardiac or structural malformation heart failure, prolonged QT interval, history of torsades de pointes, or atrioventricular (AV) block 3. Known genetic disorders, fragile x, or known brain structural abnormalities, cerebral palsy, head injury, or brain tumor 4. Known allergy to either dextromethorphan or quinidine 5. Concurrent or recent use of Monoamine oxidase inhibitor (MAOI) antidepressants pt Nuedexta 6. Concurrent use of lamotrigine or felbamate or other N-Methyl-D-aspartate (NMDA) agonists or antagonists 7. Thrombocytopenia, hepatitis, bone marrow depression or lupus-like syndrome 8. Pregnancy - sexually active females of childbearing potential must be on a reliable form of contraception 9. Other clinically significant abnormality on physical, neurological, laboratory, vital signs, that could compromise the study or be detrimental to the subject
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Maladaptive Behaviors | Baseline and 8 weeks | Demonstrate a change in frequency and intensity of maladaptive behaviors as measured by the Aberrant Behavior Checklist (ABC) Irritability subscale in subjects given Nuedexta 8 weeks over subjects given placebo. This checklist consists of 20 questions relating to behavior and the reported total score is on a scale from 0 to 60. A lower score can be interpreted as less frequent and/or less intense presentation of the undesirable behavior. The below values are the difference in ABC scores from baseline to 8 weeks. A negative difference indicates improved behavior. |
| Primary Safety Endpoints | Week 0 through week 25 | Number of serious adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Aggressive Behavior | Baseline and 8 weeks | Demonstrate a trend towards reduced aggressive behavior as measured by Overt Aggression Scale (OAS). It consists of a scale from 0 - 40, and a lower score can be interpreted as less frequent and/or less intense presentation of the undesirable behavior. Reported is the mean difference in scores from baseline to 8 weeks. A positive score indicates more aggressive behavior and a negative score indicates less aggressive behavior. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Participants who were randomized to receive either Nuedexta tablet (Dextromethorphan hydrobromide 20 mg and quinidine sulfate 10 mg) or Placebo tablet (matching Dextromethorphan hydrobromide 20 mg and quinidine sulfate 10 mg) | 13 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Second Intervention (8 Weeks) | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous | 21.68 years STANDARD_DEVIATION 3.3 |
| Autism Diagnostic Observation Schedule (ADOS) | 16.31 units on a scale STANDARD_DEVIATION 12.04 |
| Body Mass Index (BMI) | 28.00 kg/m^2 STANDARD_DEVIATION 5.86 |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 13 |
| other Total, other adverse events | 0 / 13 | 0 / 13 |
| serious Total, serious adverse events | 0 / 13 | 0 / 13 |
Outcome results
Primary
Change in Maladaptive Behaviors
Demonstrate a change in frequency and intensity of maladaptive behaviors as measured by the Aberrant Behavior Checklist (ABC) Irritability subscale in subjects given Nuedexta 8 weeks over subjects given placebo. This checklist consists of 20 questions relating to behavior and the reported total score is on a scale from 0 to 60. A lower score can be interpreted as less frequent and/or less intense presentation of the undesirable behavior. The below values are the difference in ABC scores from baseline to 8 weeks. A negative difference indicates improved behavior.
Time frame: Baseline and 8 weeks
Population: One subject withdrew at the time of crossover.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nuedexta | Change in Maladaptive Behaviors | -6.62 units on a scale | Standard Deviation 11.12 |
| Placebo | Change in Maladaptive Behaviors | -1.08 units on a scale | Standard Deviation 8.46 |
Primary
Primary Safety Endpoints
Number of serious adverse events
Time frame: Week 0 through week 25
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nuedexta | Primary Safety Endpoints | 0 Participants |
| Placebo | Primary Safety Endpoints | 0 Participants |
Secondary
Change in Aggressive Behavior
Demonstrate a trend towards reduced aggressive behavior as measured by Overt Aggression Scale (OAS). It consists of a scale from 0 - 40, and a lower score can be interpreted as less frequent and/or less intense presentation of the undesirable behavior. Reported is the mean difference in scores from baseline to 8 weeks. A positive score indicates more aggressive behavior and a negative score indicates less aggressive behavior.
Time frame: Baseline and 8 weeks
Population: One subject withdrew at the time of crossover.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nuedexta | Change in Aggressive Behavior | -1.92 units on a scale | Standard Deviation 2.78 |
| Placebo | Change in Aggressive Behavior | 0.08 units on a scale | Standard Deviation 1.88 |