Atomoxetine for Children With Acquired Attentional Disorders Following Completion of Chemotherapy for ALL

Atomoxetine for Children With Acquired Attentional Disorders Following Completion of Chemotherapy for Acute Lymphocytic Leukemia

This study is a double-blind, placebo-controlled, parallel group trial of atomoxetine (1.8 mg/kg) for the management of chemotherapy-related acquired attentional disorders in children who have survived Acute Lymphocytic Leukemia. Atomoxetine will produce a favorable impact on ADHD symptoms in children with chemo-related acquired attentional disorders.

Study Overview

• Status: Terminated
• Conditions: Attention Deficit Hyperactivity Disorder
• Intervention / Treatment: Drug: Atomoxetine

Detailed Description

The primary objective of this study is to assess the safety, tolerability and efficacy of atomoxetine as determined by the change in the ADHD-RS-IV Total score compared to placebo in the symptomatic treatment of patients diagnosed with Attention-Deficit/Hyperactivity Disorder (by DSM-IV ADHD-NOS criteria) occurring as a neuropsychological late-effect of chemotherapy used to treat Acute Lymphocytic Leukemia (ALL).

The secondary objectives are:

1. to assess the effect of once daily (AM) dosing of atomoxetine (1.8mg/kg) compared to placebo on ADHD symptoms as measured by:

   • ADHD-RS Total score inclusive of subtypes for inattention, hyperactivity and combined subtypes.
   • Clinical Global Impression-ADHD
2. to evaluate the safety and tolerability of atomoxetine compared with placebo based on treatment-emergent adverse events (AEs), laboratory tests, vital signs, physical examinations, and ECGs.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Norfolk, Virginia, United States, 23510
      • Monarch Medical Research - Child and Adolescent Neurology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Ages 6-18 years
• Must have successfully completed treatment for ALL and are currently 1-year "disease free" as judged by the investigators.
• Must meet DSM-IV criteria for "ADHD-NOS.( Attachment A) The attention deficit symptoms have been precipitated by chemotherapy-related neurological injury. Therefore, the DSM-IV category is ADHD-NOS.
• Must have an Investigator-completed ADHD-RS total and/or subscale score of ≥1.5 standard deviations above age/gender norm.
• Laboratory results, including chemistries, hematology, and urinalysis do not demonstrate clinically significant abnormalities.
• ECG demonstrates no clinically significant abnormalities
• Educational level and degree of understanding of the patient and their parents permit suitable communication between the investigators and study coordinators.
• Subjects and parents are judged to be reliable to keep appointments.
• Must be able to swallow tablets.
• Must have demonstrated compliance during their chemotherapy program.
• Must weigh > 20 kg.

Exclusion Criteria:

• Have relapsed or are having re-occurring symptoms/signs of ALL.
• Have had substantial exposure to radiation therapy (>2000: cGy) since high dose radiation treatment is associated with neurocognitive deficits or be "treatment resistant" pharmacologically.
• Past exposure to atomoxetine.
• ADHD symptoms or treatment prior to the diagnosis of ALL
• Documented bipolar disorder, psychosis, affective disorder.
• Female subjects who are pregnant or breastfeeding.
• Suicide risk.
• Seizure disorders (except history of febrile seizures).
• Histories of multiple drug allergies.
• Histories of alcohol or substance abuse.
• Prior or current medical conditions that, in the opinion of the investigators, could be exacerbated by atomoxetine.
• Sympathomimetic overactivity such as catecholamine secreting tumor.
• Use of MAOI medications.
• Have taken psychostimulants one week prior to randomization.
• Current or past history of hypertension.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 2; placebo	Drug: Atomoxetine; titration schedule: 0.5 to 1.5 mg/kg/day
Experimental: 1; atomoxetine	Drug: Atomoxetine; titration schedule: 0.5 to 1.5 mg/kg/day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary outcome is the change in the ADHD-RS total score from baseline to completion of the study.	5 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
The secondary outcome is the difference in CGI categories by the treatment versus placebo group.	5 weeks

Collaborators and Investigators

• Sponsor: Monarch Medical Research
• Collaborators: Eli Lilly and Company
• Investigators: Principal Investigator: Donald W Lewis, MD, Monarch Medical Research

Publications and helpful links

General Publications

• Mulhern RK, Friedman AG, Stone PA. Acute lymphoblastic leukemia: long-term psychological outcome. Biomed Pharmacother. 1988;42(4):243-6.
• Schuler D, Bakos M, Borsi J, Gacsaly I, Kalmanchey R, Kardos G, Koos R, Nagy C, Revesz T, Somlo P, et al. Neuropsychologic and CT examinations in leukemic patients surviving 10 or more years. Med Pediatr Oncol. 1990;18(2):123-5. doi: 10.1002/mpo.2950180207.
• Goff JR, Anderson HR Jr, Cooper PF. Distractibility and memory deficits in long-term survivors of acute lymphoblastic leukemia. J Dev Behav Pediatr. 1980 Dec;1(4):158-63.

Study record dates

Study Major Dates

• Study Start: June 1, 2006
• Primary Completion (Actual): December 1, 2007
• Study Completion (Actual): December 1, 2007

Study Registration Dates

• First Submitted: March 2, 2006
• First Submitted That Met QC Criteria: March 2, 2006
• First Posted (Estimate): March 6, 2006

Study Record Updates

• Last Update Posted (Estimate): April 26, 2012
• Last Update Submitted That Met QC Criteria: April 25, 2012
• Last Verified: April 1, 2007

More Information

Terms related to this study

• Keywords: Attention Deficit Hyperactivity Disorder
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Dyskinesias; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Disease; Attention Deficit Disorder with Hyperactivity; Hyperkinesis; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Adrenergic Uptake Inhibitors; Atomoxetine Hydrochloride
• Other Study ID Numbers: B4Z-MC-X040