Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders

Sponsor

University of Missouri, Kansas City (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04725383

Collaborator

(none)

Enrollment

Arms

42.6

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

The investigators will recruit 30 children and adolescents (15 per group x 2 groups) aged 6 to 17 years with ASD and significant repetitive behaviors that cause problems to them and to others around them. Subjects will be randomized to either amitriptyline (AMI), dosed flexibly according to response and tolerability with a maximum dose of 100mg per day or 1.5mg/kg/day, in divided doses to minimize side effects, or placebo in look-alike capsules, for 12 weeks. Rating scales, and eye-tracking will be used to measure outcomes.

Condition or Disease	Intervention/Treatment	Phase
Autism Spectrum Disorder Repetitive Compulsive Behavior	Drug: amitriptyline	Phase 3

Detailed Description

At the screening visit, investigators will perform a full history-taking, mental status examination, physical and neurological examinations, the ADI-R with a caregiver or parent to confirm autism, an EKG and complete rating scales, as well as a pregnancy test (beta-HCG) in sexually active females of childbearing age. Sexually active females of childbearing age must be on a form of birth control during the study, such as the oral contraceptive pill, intrauterine device or Depo Provera shot. A parent or guardian will sign informed consent, as appropriate, and written assent will be obtained from subjects. Blood tests for CBC and diff, CMP, amitriptyline level will be obtained at at baseline (except for amitriptyline) week 6 and 12. An eye-tracking test will be done at baseline and week 12.

Subjects will be randomized to amitriptyline (AMI) or placebo. Parents and guardians will be instructed to lock up all medications, warned regarding overdose toxicity and this will be documented in writing. Treatment will be low dose AMI or placebo for 12 weeks. Study visits will occur at weeks 0,1, 2, 3, 4, 5, 6, 8,10, and 12.

Investigators will complete a Clinical Global Impressions scale (CGI), and have the accompanying adult or parent complete rating scales, at each visit, notably the Child Yale Brown Obsessive Compulsive scale modified for Pervasive Developmental Disorder (CYBOCS-PDD), Aberrant Behavior Checklist-Irritability subscale (ABC-I), Repetitive Behavior Scale-Revised (RBS-R), ADHD-RS, adverse events form, ADI-R item 11 for phrase speech, and a concomitant treatment review form, which will also detail for example any over-the-counter medications, supplements or antibiotics taken. Also a gastrointestinal symptom form based on that used by Valicenti-McDermott et al. 2008.

At all interim visits, the PI will perform a follow-up history taking, mental status examination, vital signs, rating scales as above and study drug dispensing. Any unused capsules must be returned at each visit, to monitor compliance as well as to prevent accidental overdose. Parents and caregivers will agree to lock medication up, and will be reminded of overdose toxicity at each study visit, with written documentation.

Flexible dosing, arranged by calling the pharmacy to randomize the subject and then dispense and mail study capsules, according to the psychiatrist's instructions at each visit, to a maximum dose of 100mg/day or 1.5mg/kg/day maximum by subject weight.

Individuals and their parents or guardians will be questioned about suicidal ideation at each visit, and instructed to call study staff if that should arise. At that time the PI will arrange an urgent visit to closely assess risks of remaining in the study. In our experience suicidal ideation has not occurred. Subjects may drop out at any time however, and in the unlikely case, if warranted, be admitted to hospital for close observation.

The study will be double- blind and placebo-controlled. All investigators except a child psychiatrist co-investigator will be blinded, as will caregivers, families and subjects.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomized double-blind placebo-controlled clinicaltrial.Randomized double-blind placebo-controlled clinicaltrial.

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

All individuals involved in the study will be blinded as to drug or placebo condition, except for one child psychiatrist co-investigator who will remain unblinded and check that amitriptyline levels are not above the maximum for the laboratory therapeutic range.

Primary Purpose:

Treatment

Official Title:

Amitriptyline for Repetitive Behaviors in Children and Adolescents With Autism Spectrum Disorders

Anticipated Study Start Date :

Jun 1, 2021

Anticipated Primary Completion Date :

Jun 1, 2024

Anticipated Study Completion Date :

Dec 20, 2024

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: amitriptyline Subjects will receive active amitriptyline compounded into look-alike capsules to resemble placebo capsules. Dosing will be as tolerated, up to tid and maximum of 100mg/day or 1.5mg/kg/day, for 12 weeks.	Drug: amitriptyline Amitriptyline is a tricyclic antidepressant being studied off-label here for repetitive behaviors in autism spectrum disorders. Other Names: Elavil
Placebo Comparator: placebo Subjects in this arm will receive placebo compounded into capsules that resemble the compounded amitriptyline capsules, up to 4 capsules a day (1 qam, 1 q4pm and 2 capsules qhs), for 12 weeks.	Drug: amitriptyline Amitriptyline is a tricyclic antidepressant being studied off-label here for repetitive behaviors in autism spectrum disorders. Other Names: Elavil

Arm

Intervention/Treatment

Active Comparator: amitriptyline

Subjects will receive active amitriptyline compounded into look-alike capsules to resemble placebo capsules. Dosing will be as tolerated, up to tid and maximum of 100mg/day or 1.5mg/kg/day, for 12 weeks.

Drug: amitriptyline

Amitriptyline is a tricyclic antidepressant being studied off-label here for repetitive behaviors in autism spectrum disorders.

Other Names:

Elavil

Placebo Comparator: placebo

Subjects in this arm will receive placebo compounded into capsules that resemble the compounded amitriptyline capsules, up to 4 capsules a day (1 qam, 1 q4pm and 2 capsules qhs), for 12 weeks.

Drug: amitriptyline

Amitriptyline is a tricyclic antidepressant being studied off-label here for repetitive behaviors in autism spectrum disorders.

Other Names:

Elavil

Outcome Measures

Primary Outcome Measures

Clinical Global Impressions scale-Improvement of Much Improved (2) or Very Much Improved (1) [up to 12 weeks]
1 Very Much Improved to 7 Very Much Worse
Child Yale Brown Obsessive Compulsive Scale- Pervasive Developmental Disorders (CYBOCS-PDD) [up to 12 weeks]
0-20; high scores are more severe

Secondary Outcome Measures

Repetitive Behavior Scale-revised [up to week 12]
0-129; high scores are more severe

Other Outcome Measures

Social Responsiveness scale-2 [Baseline, week 12]
34-90; high scores are more severe
Attention-Deficit-Hyperactivity Disorder Rating Scale-Revised IV [up to week 12]
0-54; high scores are more severe
Aberrant Behavior Checklist-Irritability subscale [up to week 12]
0-45; high scores are more severe
eye-tracking test [baseline, week 6 and 12]
measured with an eye-tracking machine
ADI-R Item 16 for social vocalization/chat [baseline, week 6 and 12]
0-3; highest scores indicate poorest

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Years to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

males and females
ages 6-17 years;
diagnosis of ASD validated by the Autism Diagnostic Interview- Revised (Lord et al. 1994); CGI-S rating of at least Moderate problem CYBOCS-PDD score of at least 8 or more for compulsive behaviors (sum of items 1A, 2, 3 and 5)
Intellectual Disability if present to be no greater than moderate by history (ie IQ>35).

Exclusion Criteria:

unable to complete an EKG recording, even with low dose risperidone and alprazolam if needed an hour before, and repeated at the time (if needed), of the procedure,
QTc on EKG of 440 or more
absence of a reliable caregiver
amitriptyline allergy
previous neuroleptic malignant syndrome
seizures in the past 3 months
bipolar mood disorder
current or past psychosis
unstable medical illness
previous adequate trial of amitriptyline
using other psychotropic medications apart from melatonin for sleep or lorazepam 1mg as needed up to once a day for severe outbursts.