Atomoxetine, Placebo and Parent Management Training in Autism

NCT00844753 | Completed Phase 4 Results DMC

• 1 other identifier: 1R01MH079082-01A2
• Study Type: interventional
• Target: 128
• Locations: 1 country
• Sites: 3

Brief Summary

The study will evaluate the effectiveness of atomoxetine (Strattera) with and without Parent Management Training (PMT) in children with Autism, Asperger's Disorder, or Pervasive Developmental Disorder Not Otherwise Specified (PDDNOS) who have symptoms of Attention Deficit Hyperactivity Disorder (ADHD). This is a double-blind placebo, parallel study where the atomoxetine will have a dose titration over a 6 week period. All children will be seen weekly during this titration period, with additional visits at Week 8 and Week 10. Families assigned to the PMT arm will have an additional weekly meeting with a clinician for a total of 9 PMT visits. PMT involves teaching parents to implement behavioral interventions with their children. Subjects who are clinical responders (ADHD Responders and Compliance Responders) from the 10 week study period will be followed every 4 weeks in a 24-week extension study. Subjects who are clinical nonresponders will continue in PMT if they received PMT during the double-blind phase, and they will receive an open trial of atomoxetine if they were on placebo during the double-blind phase. All subjects (responders and nonresponders) will be invited to participate in follow-up assessments every 4 weeks for 24 weeks after the completion of the double-blind phase.

Conditions

Autism; Pervasive Development Disorder; Asperger's Disorder; Attention Deficit Hyperactivity Disorder

Keywords

Autism; PDD NOS; Attention Deficit Hyperactivity Disorder; Parent Management Training

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants Who Were Attention Deficit Hyperactivity Disorder (ADHD) Respondents

  Respondents were defined as having ≥30% decrease on the SNAP and CGI-I\<=2). The Swanson, Nolan, and Pelham (SNAP)-IV Parent and Teacher Rating Scales were used to measure ADHD and oppositional symptoms at home and school. The SNAP-IV ADHD section contains items for each of the 18 Diagnostic and Statistical Manual of Mental Disorders-IV symptoms of ADHD rated from 0 (not at all) to 3 (very much). The Clinical Global Impressions Scale (CGI) includes subscales for severity of illness and global improvement. The Severity scale is scored from 1 (normal) to 7 (extremely ill), with a rating of ≥4 required for inclusion. The Improvement score ranged from 1 (very much improved) through 4 (no change) to 7 (very much worse). The CGI was completed by a blinded rater based on parent/child interview and review of completed parent and school behavior problem questionnaires at each study visit.

  week 10

• Percentage of Participants Who Were Autism Spectrum Disorder Respondents

  Respondents were defined as having ≥30% decrease on the HSQ and CGI-I≤2). The 25-item HSQ was adapted by the Research Units on Pediatric Psychopharmacology Autism Network to evaluate behavioral noncompliance in children with autism spectrum disorder (ASD). The Home Situations Questionnaire - Pervasive Developmental Disorder (HSQ) is a 25-item parent rating scale assessing noncompliance. Parents are asked to indicate whether each item is a problem and, if so, its severity from 1 (mild) to 9 (severe). The School Situations Questionnaire (SSQ) is a 9-item teacher rating scale that assesses noncompliance. The SSQ is a companion instrument to the HSQ and uses the same rating scale. The Clinical Global Impressions Scale (CGI) includes subscales for severity of illness and global improvement. The Severity scale is scored from 1 (normal) to 7 (extremely ill),

  week 10

Study Arms (4)

1

ACTIVE COMPARATOR

Atomoxetine + Parent Management Training

Drug: atomoxetine; Behavioral: Parent Management Training

2

ACTIVE COMPARATOR

Atomoxetine without Parent Management Training

Drug: atomoxetine

3

PLACEBO COMPARATOR

Placebo + Parent Management Training

Drug: Placebo; Behavioral: Parent Management Training

4

PLACEBO COMPARATOR

Placebo without Parent Management Training

Drug: Placebo

Interventions

atomoxetine DRUG

atomoxetine

1; 2

Placebo DRUG

Placebo + parent management treatment

3; 4

Parent Management Training BEHAVIORAL

1; 3

Eligibility Criteria

• Age: 5 Years - 14 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Children 5 yrs to 14 years 11 mos with clinical diagnosis of Autism, Asperger's Disorder, or PDDNOS based upon the ADI-R and clinical evaluation by DSM-IV criteria,
• Mental age equal to or greater than 24 months,
• ADHD symptoms based upon the CASI and clinical confirmed diagnosis,
• CGIS-S rating of 4 or grater for ADHD symptoms,
• A mean item score of \>1.5 on both the Parent and Teacher (non-parent caregiver) SNAP-IV 18 ADHD symptoms or the 9-symptom hyperactive-impulsive subscale (symptoms must be cross-situational),
• Reliable care provider available to bring subject to clinic visits and weekly sessions.

You may not qualify if:

• DSM-IV diagnosis of schizophrenia, schizoaffective disorder psychotic disorder NOS,bipolar disorder, or major depression (if accompanied by a family history of bipolar disorder) based upon evidence of suicidality, CASI, and clinical interview/history,
• Prior failed adequate trial of atomoxetine,
• Use of other psychotropic medications that produce CNS effects,
• Diagnosis of bipolar disorder, major depression, hypertension, cardiovascular disease, narrow angle glaucoma, other significant physical illness,
• Pregnancy or sexually active females (intercourse in the past 6 months, reported by either the subject or caregiver),
• Currently on effective medication treatment for ADHD,
• Prior involvement in Parent Management Training or other similar program,
• Currently on albuterol or taking beta blockers,
• Taking supplements or other complementary medical treatments where dose cannot be held at current level for duration of study

Sponsors & Collaborators

• University of Rochester: lead
• University of Pittsburgh: collaborator
• Ohio State University: collaborator

Study Sites (3)

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Ohio State University

Columbus, Ohio, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Location

Related Publications (7)

• Chowdhury M, Aman MG, Scahill L, Swiezy N, Arnold LE, Lecavalier L, Johnson C, Handen B, Stigler K, Bearss K, Sukhodolsky D, McDougle CJ. The Home Situations Questionnaire-PDD version: factor structure and psychometric properties. J Intellect Disabil Res. 2010 Mar;54(3):281-91. doi: 10.1111/j.1365-2788.2010.01259.x.

  PMID: 20377705 RESULT

• Barkley, R. A., & Edelbrock, C. (1987). Assessing situational variation in children's problem behaviors: The Home and School Situations Questionnaires. In R. Prinz (Ed.), Advances in behavioral assessment of children and families (pp. 157-176). Greenwich, CT: JAI Press Inc

  RESULT

• Iffland M, Livingstone N, Jorgensen M, Hazell P, Gillies D. Pharmacological intervention for irritability, aggression, and self-injury in autism spectrum disorder (ASD). Cochrane Database Syst Rev. 2023 Oct 9;10(10):CD011769. doi: 10.1002/14651858.CD011769.pub2.

  PMID: 37811711 DERIVED

• Arnold LE, Ober N, Aman MG, Handen B, Smith T, Pan X, Hyman SL, Hollway J, Lecavalier L, Page K, Rice R Jr. A 1.5-Year Follow-Up of Parent Training and Atomoxetine for Attention-Deficit/Hyperactivity Disorder Symptoms and Noncompliant/Disruptive Behavior in Autism. J Child Adolesc Psychopharmacol. 2018 Jun;28(5):322-330. doi: 10.1089/cap.2017.0134. Epub 2018 Apr 25.

  PMID: 29694241 DERIVED

• Lecavalier L, Pan X, Smith T, Handen BL, Arnold LE, Silverman L, Tumuluru RV, Hollway J, Aman MG. Parent Stress in a Randomized Clinical Trial of Atomoxetine and Parent Training for Children with Autism Spectrum Disorder. J Autism Dev Disord. 2018 Apr;48(4):980-987. doi: 10.1007/s10803-017-3345-4.

  PMID: 29022125 DERIVED

• Smith T, Aman MG, Arnold LE, Silverman LB, Lecavalier L, Hollway J, Tumuluru R, Hyman SL, Buchan-Page KA, Hellings J, Rice RR Jr, Brown NV, Pan X, Handen BL. Atomoxetine and Parent Training for Children With Autism and Attention-Deficit/Hyperactivity Disorder: A 24-Week Extension Study. J Am Acad Child Adolesc Psychiatry. 2016 Oct;55(10):868-876.e2. doi: 10.1016/j.jaac.2016.06.015. Epub 2016 Aug 2.

  PMID: 27663942 DERIVED

• Handen BL, Aman MG, Arnold LE, Hyman SL, Tumuluru RV, Lecavalier L, Corbett-Dick P, Pan X, Hollway JA, Buchan-Page KA, Silverman LB, Brown NV, Rice RR Jr, Hellings J, Mruzek DW, McAuliffe-Bellin S, Hurt EA, Ryan MM, Levato L, Smith T. Atomoxetine, Parent Training, and Their Combination in Children With Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder. J Am Acad Child Adolesc Psychiatry. 2015 Nov;54(11):905-15. doi: 10.1016/j.jaac.2015.08.013. Epub 2015 Sep 3.

  PMID: 26506581 DERIVED

MeSH Terms

Conditions

Autistic Disorder; Child Development Disorders, Pervasive; Asperger Syndrome; Attention Deficit Disorder with Hyperactivity

Interventions

Atomoxetine Hydrochloride

Condition Hierarchy (Ancestors)

Autism Spectrum Disorder; Neurodevelopmental Disorders; Mental Disorders; Attention Deficit and Disruptive Behavior Disorders

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals

Results Point of Contact

• Title: Ben Handen
• Organization: University of Pittsburgh

HandenBL@upmc.edu

412-235-5452

Study Officials

• Benjamin Handen, PhD

  University of Pittsburgh Medical Center

  PRINCIPAL INVESTIGATOR

• Michael Aman, PhD

  Ohio State University

  PRINCIPAL INVESTIGATOR

• Tristram Smith, PhD

  University of Rochester

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: June 6, 2008
• First Posted: February 16, 2009
• Study Start: October 1, 2008
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: February 4, 2016
• Results First Posted: February 4, 2016

Record last verified: 2016-01

Locations

US (3)