Autism
Conditions
Keywords
Autism
Brief summary
The purpose of this study is to determine whether CM-AT is safe and effective in treating the core symptoms of autism in children with all levels of fecal chymotrypsin.
Detailed description
Autism is clearly a significant cause of disability in the pediatric population. Many children with Autism exhibit impaired protein digestion which may or may not manifest in self-restricted diets. The inability to digest protein affects the availability of essential amino acids in the body. CM-AT is designed to enhance protein digestion thereby potentially restoring the pool of essential amino acids. Essential amino acids play a critical role in the expression of several genes important to neurological function and serve as precursors to key neurotransmitters such as serotonin and dopamine. CM-AT is a proprietary enzyme that is designed as a granulated powder taken three times daily.
Interventions
DRUGCM-AT
Single unit dose powder of active substance (CM-AT) administered 3 times per day for 90 days
DRUGPLACEBO
Single unit dose powder of non-active substance administered 3 times per day for 90 days
Sponsors
Curemark
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
3 Years to 8 Years
Healthy volunteers
Yes
Inclusion criteria
* Meets the current Diagnostic and Statistical Manual with Mental Disorders (DSM-IV-TR) for Autism (Autistic Disorder), screened by SCQ and confirmed by ADI-R;
Exclusion criteria
* Patient weighing \< 13kg (28.6 lbs) * Previous allergy to porcine (pork) products * Previous history of severe head trauma or stroke, loss of consciousness, seizure (or need for seizure medication either present or past) within one year of entering study or uncontrolled systemic disease * Diagnosis of: HIV, cerebral palsy, endocrine disorder, pancreatic disease, muscular dystrophy, known genetic disorder, blood dyscrasia, ongoing GI disease * Evidence of severe, moderate or uncontrolled systemic disease; and/or any co-morbid condition which in the Investigator's or Medical Director's opinion makes it undesirable for the subject to participate in the study or jeopardizes compliance with the protocol; * Within 30 days of starting the study, certain supplementation, chelation or dietary restriction (a 30 day washout period would be required for inclusion); * Ongoing dietary restriction for allergy or other reasons except nut allergies (lactose-free allowable); * Use of of any stimulant medication must be discontinued 5 days prior to entering the study. * Subject must have a stable dose of SSRI's for at least 30 days. * Inability to ingest study drug and/or follow prescribed dosing schedule
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Outcome Measurements to Determine Efficacy of Treatment With CM-AT Versus Placebo for Changes in the Aberrant Behavior Checklist Subscale for Irritability / Agitation (ABC-I) Between Baseline and Week 12/Termination Visit | Screening through Week 12/Termination | Primary outcome measurements to determine efficacy of treatment with CM-AT versus Placebo for changes in the Aberrant Behavior Checklist (ABC) - Community sub scale for Irritability/Agitation (ABC-I) between baseline (subject's initial measurement) and Week 12/Termination (subject's final measurement) visit. Participants were between 3 through to 6 years old inclusive and took 900mg CM-AT or Placebo three times daily. The ABC-I is one of five discrete sub scales measured by the ABC. The scale range is 0-45. A higher score reflects higher severity of symptoms (irritability). Scores are obtained via Parent Rated Questionnaire. Parents respond to a series of questions on a scale directly into an electronic data capture system (EDC), responding: 0 = not at all a problem 1 = the behavior is a problem but slight in degree 2 = the problem is moderately serious 3 = the problem is severe in degree. The score was automatically calculated by the EDC. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary Outcome Measurements of Changes in the Aberrant Behavior Checklist Checklist Subscale for Lethargy / Social Withdrawal (ABC-L) Between Baseline and Week 12/Termination Visit | Screening through Week 12/Termination. | Secondary outcome measurements to determine efficacy of treatment with CM-AT versus Placebo for changes in the Aberrant Behavior Checklist- Community (ABC) sub scale for Lethargy / Social Withdrawal (ABC-L) between baseline (subject's initial measurement) and Week 12/Termination (subject's final measurement) visit. Participants were between 3 through to 6 years old inclusive and took 900mg CM-AT or Placebo three times daily. The ABC-L is one of five discrete sub scales measured by the ABC. The scale range is 0-48. A higher score reflects higher severity of symptoms (lethargy). Scores are obtained via Parent Rated Questionnaire. Parents respond to a series of questions on a scale directly into an electronic data capture system (EDC), responding: 0 = not at all a problem 1 = the behavior is a problem but slight in degree 2 = the problem is moderately serious 3 = the problem is severe in degree. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited across 33 sites in the USA. The First Subject First Visit (FSFV) occurred on 03 June 2015 (First screening visit date) and the Last Subject Last Visit (LSLV) occurred on 20 December 2017.
Pre-assignment details
Participants were screened for autistic disorder using the Diagnostic Statistical Manual of Mental Disorders Fourth Edition - Text Revised (DSM-IV-TR); and the Social Communication Questionnaire (SCQ), with diagnostic confirmation by the Autism Diagnostic Interview-Revised (ADI-R). All qualifying participants were given a 2 week run-in period and then reassessed for eligibility and then randomized.
Participants by arm
| Arm | Count |
|---|---|
| CM-AT Active substance in single unit dose powder
CM-AT: Single unit dose powder of active substance, 900mg, (CM-AT) administered 3 times per day, one at each meal for 90 days. Participants were between 3 and 8 years old inclusive. | 92 |
| Placebo Placebo powder of inactive substance
PLACEBO: Single unit dose powder of non-active substance, 900mg, (Placebo) administered 3 times per day, one at each meal for 90 days. Participants were between 3 and 8 years old inclusive. | 98 |
| Total | 190 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 3 |
| Overall Study | Lost to Follow-up | 4 | 1 |
| Overall Study | Non-Compliance | 8 | 2 |
| Overall Study | Protocol Violation | 1 | 4 |
| Overall Study | Withdrawal by Subject | 6 | 8 |
Baseline characteristics
| Characteristic | CM-AT | Placebo | Total |
|---|---|---|---|
| ABC-I | 22.2 units on a scale STANDARD_DEVIATION 7.6 | 23.4 units on a scale STANDARD_DEVIATION 7.9 | 22.8 units on a scale STANDARD_DEVIATION 7.75 |
| Age, Categorical <=18 years | 92 Participants | 98 Participants | 190 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 5.7 Years STANDARD_DEVIATION 1.6 | 5.7 Years STANDARD_DEVIATION 1.6 | 5.7 Years STANDARD_DEVIATION 1.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 20 Participants | 80 Participants | 100 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 71 Participants | 18 Participants | 89 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 12 Participants | 10 Participants | 22 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 8 Participants | 18 Participants |
| Race (NIH/OMB) More than one race | 7 Participants | 6 Participants | 13 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) White | 61 Participants | 70 Participants | 131 Participants |
| Region of Enrollment United States | 92 participants | 98 participants | 190 participants |
| Sex: Female, Male Female | 21 Participants | 19 Participants | 40 Participants |
| Sex: Female, Male Male | 71 Participants | 79 Participants | 150 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 92 | 0 / 98 |
| other Total, other adverse events | 79 / 92 | 90 / 98 |
| serious Total, serious adverse events | 0 / 92 | 0 / 98 |
Outcome results
Primary
Primary Outcome Measurements to Determine Efficacy of Treatment With CM-AT Versus Placebo for Changes in the Aberrant Behavior Checklist Subscale for Irritability / Agitation (ABC-I) Between Baseline and Week 12/Termination Visit
Primary outcome measurements to determine efficacy of treatment with CM-AT versus Placebo for changes in the Aberrant Behavior Checklist (ABC) - Community sub scale for Irritability/Agitation (ABC-I) between baseline (subject's initial measurement) and Week 12/Termination (subject's final measurement) visit. Participants were between 3 through to 6 years old inclusive and took 900mg CM-AT or Placebo three times daily. The ABC-I is one of five discrete sub scales measured by the ABC. The scale range is 0-45. A higher score reflects higher severity of symptoms (irritability). Scores are obtained via Parent Rated Questionnaire. Parents respond to a series of questions on a scale directly into an electronic data capture system (EDC), responding: 0 = not at all a problem 1 = the behavior is a problem but slight in degree 2 = the problem is moderately serious 3 = the problem is severe in degree. The score was automatically calculated by the EDC.
Time frame: Screening through Week 12/Termination
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CM-AT | Primary Outcome Measurements to Determine Efficacy of Treatment With CM-AT Versus Placebo for Changes in the Aberrant Behavior Checklist Subscale for Irritability / Agitation (ABC-I) Between Baseline and Week 12/Termination Visit | -8.0 units on a scale | Standard Deviation 7.47 |
| Placebo | Primary Outcome Measurements to Determine Efficacy of Treatment With CM-AT Versus Placebo for Changes in the Aberrant Behavior Checklist Subscale for Irritability / Agitation (ABC-I) Between Baseline and Week 12/Termination Visit | -5.5 units on a scale | Standard Deviation 9.19 |
p-value: 0.03895% CI: [-4.98, -0.14]ANCOVA
Secondary
Secondary Outcome Measurements of Changes in the Aberrant Behavior Checklist Checklist Subscale for Lethargy / Social Withdrawal (ABC-L) Between Baseline and Week 12/Termination Visit
Secondary outcome measurements to determine efficacy of treatment with CM-AT versus Placebo for changes in the Aberrant Behavior Checklist- Community (ABC) sub scale for Lethargy / Social Withdrawal (ABC-L) between baseline (subject's initial measurement) and Week 12/Termination (subject's final measurement) visit. Participants were between 3 through to 6 years old inclusive and took 900mg CM-AT or Placebo three times daily. The ABC-L is one of five discrete sub scales measured by the ABC. The scale range is 0-48. A higher score reflects higher severity of symptoms (lethargy). Scores are obtained via Parent Rated Questionnaire. Parents respond to a series of questions on a scale directly into an electronic data capture system (EDC), responding: 0 = not at all a problem 1 = the behavior is a problem but slight in degree 2 = the problem is moderately serious 3 = the problem is severe in degree.
Time frame: Screening through Week 12/Termination.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CM-AT | Secondary Outcome Measurements of Changes in the Aberrant Behavior Checklist Checklist Subscale for Lethargy / Social Withdrawal (ABC-L) Between Baseline and Week 12/Termination Visit | -7.9 units on a scale | Standard Deviation 6.96 |
| Placebo | Secondary Outcome Measurements of Changes in the Aberrant Behavior Checklist Checklist Subscale for Lethargy / Social Withdrawal (ABC-L) Between Baseline and Week 12/Termination Visit | -6.6 units on a scale | Standard Deviation 9.52 |
p-value: 0.32595% CI: [-3.21, 1.07]ANCOVA