Atomoxetine and Huntington's Disease

NCT00368849 | Completed Phase 2 Results DMC

• 1 other identifier: 200508775
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to evaluate the effect of atomoxetine (also known as Strattera) compared to placebo (inactive substance) on daily activities such as attention and focus, thinking ability and muscle movements in subjects with early Huntington Disease (HD) and attention deficit disorder (ADD).

Conditions

Huntington Disease; Chorea

Keywords

Huntington Disease; Chorea; Attention; ADHD; ADD; Strattera; Atomoxetine

Outcome Measures

Primary Outcomes (3)

• Conners' Adult Attention Rating Scale (CAARS)

  The Conners' Adult Attention Rating Scale (CAARS) is one of the most frequently used self-rating measures for adult Attention Deficit Hyperactivity Disorder (ADHD) and was given as a self-report measure of attention. It has 66 items with each item ranging from 0 to 3 points. Higher total scores represent greater impairment. The outcome reported was change in score from baseline for each treatment arm.

  There are two time points for this measure: baseline and after 4 weeks of treatment

• Attention Composite Score

  The attention composite comprises performance on Wechsler Adult Intelligence Scale III Symbol-Digit and Letter Number Sequencing Subtests, Trail Making Test Part A, computerized simple-choice reaction time, and computerized working memory (i.e., 2-Back). The composite score is the average combined z score for each test. Higher, positive values indicate better than average performance and negative and lower values indicate worse than average. The outcome reported was change in score from baseline for each treatment arm.

  There are two time points for this measure: baseline and after 4 weeks of treatment

• Executive Composite Score

  The executive composite comprises performance on Trail Making Test Part B, Stroop Color and Word Test, and the Controlled Oral Word Association Test (i.e., Verbal Fluency). The composite score is the average combined z score for each test. Positive values indicate better than average performance and negative values worse than average. The outcome reported was change in score from baseline for each treatment arm.

  There are two time points for this measure: baseline and after 4 weeks of treatment

Secondary Outcomes (2)

• Symptom Checklist-90-Revised (SCL-90-R)

  There are two time points for this measure: baseline and after 4 weeks of treatment

• Unified Huntington Disease Rating Scale (UHDRS) Total Motor Score

  There are two time points for this measure: baseline and after 4 weeks of treatment

Study Arms (2)

40 milligram twice a day atomoxetine

EXPERIMENTAL

Participants received 40 milligram twice a day atomoxetine for 4 weeks.

Drug: atomoxetine

Twice a day matching placebo

PLACEBO COMPARATOR

Participants received twice a day matching placebo for 4 weeks.

Drug: Matching Placebo

Interventions

atomoxetine DRUG

This study utilizes a crossover design. Accordingly, half of the participants receive 40 milligram twice a day atomoxetine at arm one while the remaining half receive this intervention at arm two.

Also known as: Strattera

40 milligram twice a day atomoxetine

Matching Placebo DRUG

This study utilizes a crossover design. Accordingly, half of the participants receive twice a day matching placebo at arm one while the remaining half receive this intervention at arm two.

Also known as: Sugar pill

Twice a day matching placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed Huntington's disease (HD) diagnosis
• Age 18 to 65
• Must have mild HD
• Must have complaints of poor attention

You may not qualify if:

• Childhood history of attention deficit hyperactivity disorder (ADHD) symptoms
• Diagnosis of schizophrenia, bipolar affective disorder, dementia, delirium or severe anxiety
• Current use of a monoamine oxidase inhibitor (MAOI) medication
• Pregnancy
• Uncontrolled hypertension
• Tachycardia
• Cardiovascular or cerebrovascular disease
• History of a loss of consciousness for greater than (or equal to) 5 minutes
• Having any neurological disorder or insult other than Huntington disease

Sponsors & Collaborators

• University of Iowa: lead
• Eli Lilly and Company: collaborator

Study Sites (1)

The University of Iowa

Iowa City, Iowa, 52242, United States

Location

Related Publications (16)

• A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group. Cell. 1993 Mar 26;72(6):971-83. doi: 10.1016/0092-8674(93)90585-e.

  PMID: 8458085 BACKGROUND

• Campodonico JR, Aylward E, Codori AM, Young C, Krafft L, Magdalinski M, Ranen N, Slavney PR, Brandt J. When does Huntington's disease begin? J Int Neuropsychol Soc. 1998 Sep;4(5):467-73. doi: 10.1017/s1355617798455061.

  PMID: 9745236 BACKGROUND

• Lawrence AD, Hodges JR, Rosser AE, Kershaw A, ffrench-Constant C, Rubinsztein DC, Robbins TW, Sahakian BJ. Evidence for specific cognitive deficits in preclinical Huntington's disease. Brain. 1998 Jul;121 ( Pt 7):1329-41. doi: 10.1093/brain/121.7.1329.

  PMID: 9679784 BACKGROUND

• Paulsen JS, Zhao H, Stout JC, Brinkman RR, Guttman M, Ross CA, Como P, Manning C, Hayden MR, Shoulson I; Huntington Study Group. Clinical markers of early disease in persons near onset of Huntington's disease. Neurology. 2001 Aug 28;57(4):658-62. doi: 10.1212/wnl.57.4.658.

  PMID: 11524475 BACKGROUND

• Marder K, Zhao H, Myers RH, Cudkowicz M, Kayson E, Kieburtz K, Orme C, Paulsen J, Penney JB Jr, Siemers E, Shoulson I. Rate of functional decline in Huntington's disease. Huntington Study Group. Neurology. 2000 Jan 25;54(2):452-8. doi: 10.1212/wnl.54.2.452.

  PMID: 10668713 BACKGROUND

• Gomez-Tortosa E, MacDonald ME, Friend JC, Taylor SA, Weiler LJ, Cupples LA, Srinidhi J, Gusella JF, Bird ED, Vonsattel JP, Myers RH. Quantitative neuropathological changes in presymptomatic Huntington's disease. Ann Neurol. 2001 Jan;49(1):29-34.

  PMID: 11198293 BACKGROUND

• Beglinger, L. et al. The association between speed of processing and cerebral white matter volume in patients with mild Huntington's disease [abstract]. Poster session accepted at the Annual Meeting of the Cognitive Neuroscience Society, April, 2004

  BACKGROUND

• Halliday GM, McRitchie DA, Macdonald V, Double KL, Trent RJ, McCusker E. Regional specificity of brain atrophy in Huntington's disease. Exp Neurol. 1998 Dec;154(2):663-72. doi: 10.1006/exnr.1998.6919.

  PMID: 9878201 BACKGROUND

• Nopoulos, P. et al., (under review). Structural Brain Abnormalities in pre-symptomatic Huntington's disease.

  BACKGROUND

• Aylward EH, Anderson NB, Bylsma FW, Wagster MV, Barta PE, Sherr M, Feeney J, Davis A, Rosenblatt A, Pearlson GD, Ross CA. Frontal lobe volume in patients with Huntington's disease. Neurology. 1998 Jan;50(1):252-8. doi: 10.1212/wnl.50.1.252.

  PMID: 9443488 BACKGROUND

• Casey BJ, Castellanos FX, Giedd JN, Marsh WL, Hamburger SD, Schubert AB, Vauss YC, Vaituzis AC, Dickstein DP, Sarfatti SE, Rapoport JL. Implication of right frontostriatal circuitry in response inhibition and attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 1997 Mar;36(3):374-83. doi: 10.1097/00004583-199703000-00016.

  PMID: 9055518 BACKGROUND

• Hale TS, Hariri AR, McCracken JT. Attention-deficit/hyperactivity disorder: perspectives from neuroimaging. Ment Retard Dev Disabil Res Rev. 2000;6(3):214-9. doi: 10.1002/1098-2779(2000)6:33.0.CO;2-M.

  PMID: 10982499 BACKGROUND

• Heilman KM, Voeller KK, Nadeau SE. A possible pathophysiologic substrate of attention deficit hyperactivity disorder. J Child Neurol. 1991;6 Suppl:S76-81. doi: 10.1177/0883073891006001s09.

  PMID: 2002218 BACKGROUND

• Spencer T, Biederman J, Wilens T, Prince J, Hatch M, Jones J, Harding M, Faraone SV, Seidman L. Effectiveness and tolerability of tomoxetine in adults with attention deficit hyperactivity disorder. Am J Psychiatry. 1998 May;155(5):693-5. doi: 10.1176/ajp.155.5.693.

  PMID: 9585725 BACKGROUND

• Michelson D, Adler L, Spencer T, Reimherr FW, West SA, Allen AJ, Kelsey D, Wernicke J, Dietrich A, Milton D. Atomoxetine in adults with ADHD: two randomized, placebo-controlled studies. Biol Psychiatry. 2003 Jan 15;53(2):112-20. doi: 10.1016/s0006-3223(02)01671-2.

  PMID: 12547466 BACKGROUND

• Conners, CK et al. Conners' Adult ADHD Rating Scales (CAARS). 1999. North Tonawanda, NY: Multi-Health Systems.

  BACKGROUND

Related Links

• University of Iowa Huntington's Disease Center of Excellence

MeSH Terms

Conditions

Huntington Disease; Chorea; Attention Deficit Disorder with Hyperactivity

Interventions

Atomoxetine Hydrochloride; Sugars

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Dementia; Dyskinesias; Movement Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Carbohydrates

Limitations and Caveats

We cannot rule out carryover effects. Additionally, the sample size may be too low to detect small treatment changes, the treatment duration may have been too brief, and our participants had only early-stage HD which may have limited the drug effect.

Results Point of Contact

• Title: Leigh J. Beglinger, Ph.D.
• Organization: The University of Iowa

leigh-beglinger@uiowa.edu

319-335-8765

Study Officials

• Leigh J Beglinger, Ph.D.

  University of Iowa

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: August 24, 2006
• First Posted: August 29, 2006
• Study Start: November 1, 2005
• Primary Completion: February 1, 2008
• Study Completion: February 1, 2008
• Last Updated: December 20, 2012
• Results First Posted: November 27, 2012

Record last verified: 2012-12

Locations

US (1)