Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders

NCT04725383 | Terminated Phase 3 DMC FDA Drug

• 2 other identifiers: 201598417-055
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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.

Conditions

Autism Spectrum Disorder; Repetitive Compulsive Behavior

Keywords

amitriptyline; autism; repetitive behaviors

Outcome Measures

Primary Outcomes (2)

• Clinical Global Impressions scale-Improvement of Much Improved (2) or Very Much Improved (1)

  1 Very Much Improved to 7 Very Much Worse

  up to 10 weeks

• Child Yale Brown Obsessive Compulsive Scale- Pervasive Developmental Disorders (CYBOCS-PDD)

  0-20; high scores are more severe

  up to 10 weeks

Secondary Outcomes (1)

• Repetitive Behavior Scale-revised

  up to week 10

Other Outcomes (4)

• Social Responsiveness scale-2

  Baseline, week 10

• Attention-Deficit-Hyperactivity Disorder Rating Scale-Revised IV

  up to week 10

• Aberrant Behavior Checklist-Irritability subscale

  up to week 10

Study Arms (2)

amitriptyline

ACTIVE COMPARATOR

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.

Drug: amitriptyline

placebo

PLACEBO COMPARATOR

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.

Drug: amitriptyline

Interventions

amitriptyline DRUG

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

Also known as: Elavil

amitriptyline; placebo

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Missouri, Kansas City: lead

Study Sites (1)

University Health Behavioral Health Canvas Building

Kansas City, Missouri, 64108, United States

Location

Related Publications (1)

• 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.

  PMID: 23135317 BACKGROUND

MeSH Terms

Conditions

Autism Spectrum Disorder; Autistic Disorder

Interventions

Amitriptyline

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Dibenzocycloheptenes; Benzocycloheptenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Jessica A. Hellings, MD

  University of Kansas City-Missouri and Truman Behavioral Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Psychiatry

Model Details: Randomized double-blind placebo-controlled clinical trial.

Study Record Dates

• First Submitted: January 7, 2021
• First Posted: January 26, 2021
• Study Start: November 1, 2023
• Primary Completion: May 23, 2025
• Study Completion: May 23, 2025
• Last Updated: May 30, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)