Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders
Primary Purpose
Autism Spectrum Disorder, Repetitive Compulsive Behavior
Status
Not yet recruiting
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
amitriptyline
Sponsored by
About this trial
This is an interventional treatment trial for Autism Spectrum Disorder focused on measuring amitriptyline, autism, repetitive behaviors
Eligibility Criteria
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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
amitriptyline
placebo
Arm Description
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 10 weeks.
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 10 weeks.
Outcomes
Primary Outcome Measures
Clinical Global Impressions scale-Improvement of Much Improved (2) or Very Much Improved (1)
1 Very Much Improved to 7 Very Much Worse
Child Yale Brown Obsessive Compulsive Scale- Pervasive Developmental Disorders (CYBOCS-PDD)
0-20; high scores are more severe
Secondary Outcome Measures
Repetitive Behavior Scale-revised
0-129; high scores are more severe
Full Information
NCT ID
NCT04725383
First Posted
January 7, 2021
Last Updated
June 19, 2023
Sponsor
University of Missouri, Kansas City
1. Study Identification
Unique Protocol Identification Number
NCT04725383
Brief Title
Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders
Official Title
Amitriptyline for Repetitive Behaviors in Children and Adolescents With Autism Spectrum Disorders
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
July 1, 2023 (Anticipated)
Primary Completion Date
June 1, 2025 (Anticipated)
Study Completion Date
December 20, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Missouri, Kansas City
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. 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 10 weeks. Rating scales will be used to measure outcomes.
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 10.
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, and 10.
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 psychiatry co-investigator will be blinded, as will caregivers, families and subjects.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Autism Spectrum Disorder, Repetitive Compulsive Behavior
Keywords
amitriptyline, autism, repetitive behaviors
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Randomized double-blind placebo-controlled clinical trial.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
All individuals involved in the study will be blinded as to drug or placebo condition, except for one psychiatry co-investigator who will remain unblinded and check that amitriptyline levels are not above the maximum for the laboratory therapeutic range.
Allocation
Randomized
Enrollment
30 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
amitriptyline
Arm Type
Active Comparator
Arm Description
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 10 weeks.
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
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 10 weeks.
Intervention Type
Drug
Intervention Name(s)
amitriptyline
Other Intervention Name(s)
Elavil
Intervention Description
Amitriptyline is a tricyclic antidepressant being studied off-label here for repetitive behaviors in autism spectrum disorders.
Primary Outcome Measure Information:
Title
Clinical Global Impressions scale-Improvement of Much Improved (2) or Very Much Improved (1)
Description
1 Very Much Improved to 7 Very Much Worse
Time Frame
up to 10 weeks
Title
Child Yale Brown Obsessive Compulsive Scale- Pervasive Developmental Disorders (CYBOCS-PDD)
Description
0-20; high scores are more severe
Time Frame
up to 10 weeks
Secondary Outcome Measure Information:
Title
Repetitive Behavior Scale-revised
Description
0-129; high scores are more severe
Time Frame
up to week 10
Other Pre-specified Outcome Measures:
Title
Social Responsiveness scale-2
Description
34-90; high scores are more severe
Time Frame
Baseline, week 10
Title
Attention-Deficit-Hyperactivity Disorder Rating Scale-Revised IV
Description
0-54; high scores are more severe
Time Frame
up to week 10
Title
Aberrant Behavior Checklist-Irritability subscale
Description
0-45; high scores are more severe
Time Frame
up to week 10
Title
ADI-R Item 16 for social vocalization/chat
Description
0-3; highest scores indicate poorest
Time Frame
baseline, week 6 and 10
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jessica A Hellings, MD
Phone
816-404-6202
Email
Jessica.Hellings@uhkc.org
First Name & Middle Initial & Last Name or Official Title & Degree
Aderonke Oyetunji, MD
Email
Aderonke.Oyetunji@tmcmed.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jessica A. Hellings, MD
Organizational Affiliation
University of Kansas City-Missouri and Truman Behavioral Health
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
23135317
Citation
Bhatti I, Thome A, Smith PO, Cook-Wiens G, Yeh HW, Gaffney GR, Hellings JA. A retrospective study of amitriptyline in youth with autism spectrum disorders. J Autism Dev Disord. 2013 May;43(5):1017-27. doi: 10.1007/s10803-012-1647-0.
Results Reference
background
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Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders
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