Atomoxetine and Huntington's Disease - Full Text View

Sponsor:	University of Iowa
Collaborator:	Eli Lilly and Company
Information provided by:	University of Iowa
ClinicalTrials.gov Identifier:	NCT00368849

Purpose

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 HD and attention deficit disorder.

Condition	Intervention	Phase
Huntington Disease Chorea	Drug: atomoxetine	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Atomoxetine for Attention Deficits in Adults With Mild HD: A Randomized, Placebo-Controlled Crossover Study

Resource links provided by NLM:

Genetics Home Reference related topics: chorea-acanthocytosis familial paroxysmal nonkinesigenic dyskinesia Huntington disease McLeod neuroacanthocytosis syndrome

MedlinePlus related topics: Huntington's Disease

Drug Information available for: Atomoxetine hydrochloride Atomoxetine

U.S. FDA Resources

Further study details as provided by University of Iowa:

Primary Outcome Measures:

Primary dependent variables will be CAARS score and a cognitive summary score. [ Time Frame: Not available ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Secondary measures include individual cognitive tests, UHDRS motor score and SCL-90-R global index score. [ Time Frame: Not available ] [ Designated as safety issue: No ]

Enrollment:	20
Study Start Date:	November 2005
Study Completion Date:	February 2008
Primary Completion Date:	February 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Placebo or 40mg bid atomoxetine, using a 1:1 allocation	Drug: atomoxetine This study utilizes a crossover design. Participants receive 40mg bid atomoxetine or placebo at arm 01 and arm 02 using a 1:1 allocation Other Name: Strattera
Experimental: 2 40mg bid atomoxetine or placebo, using a 1:1 allocation	Drug: atomoxetine This study utilizes a crossover design. Participants receive 40mg bid atomoxetine or placebo at arm 01 and arm 02 using a 1:1 allocation Other Name: Strattera

Detailed Description:

No medications have been investigated to improve attention and executive functions in patients with Huntington's disease, despite the evidence that these cognitive domains can be abnormal even before motor symptom onset. Because cognitive symptoms are highly associated with functional disability, treatments aimed at improving cognitive functions would be of significant benefit to patients in the early stages of the disease. Atomoxetine is the ideal choice for such a trial. It has proven efficacy in adults with ADHD and it selectively targets norepinephrine and dopamine in the prefrontal cortex rather than in subcortical areas. This selectivity is an advantage for patients with HD, because motor side effects are less likely to be facilitated than with a psychostimulant. The present study is a feasibility study in which we propose to administer either 80 mg atomoxetine for 4 weeks or placebo to 20 patients with early HD and who also complain of mild cognitive symptoms. The groups will then crossover to the other condition (atomoxetine or placebo). Participants will be assessed on measures of ADHD symptoms and a sensitive battery of neuropsychological tests. Based on the shared neural circuitry in ADHD and HD, and the demonstrated effectiveness of atomoxetine on attention in adults with ADHD, improved performance on cognitive tests of attention and executive functions and on subjects' report of ADHD symptoms are expected in the atomoxetine treatment phase. No changes in motor status are predicted during the study.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Confirmed Huntington's disease diagnosis
Age 18-65
Must have mild HD
Must have complaints of poor attention

Exclusion Criteria:

Childhood history of ADHD symptoms
Diagnosis of schizophrenia, bipolar affective disorder, dementia, delirium or severe anxiety
Current use of an MAOI
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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00368849

Locations

United States, Iowa
The University of Iowa
Iowa City, Iowa, United States, 52242

Sponsors and Collaborators

University of Iowa

Eli Lilly and Company

Investigators

Principal Investigator:

Leigh J Beglinger, Ph.D.

The University of Iowa

More Information

Additional Information:

University of Iowa Huntington's Disease Center of Excellence This link exits the ClinicalTrials.gov site

Publications:

[No authors listed] 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.

Campodonico, J. et al. When does Huntington's Disease begin? J Intnl Neuropsychol Soc, 4: 1998, 467-473.

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.

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.

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. Erratum in: Neurology 2000 Apr 25;54(8):1712.

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.

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

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.

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.

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.

Hale TS, Hariri AR, McCracken JT. Attention-deficit/hyperactivity disorder: perspectives from neuroimaging. Ment Retard Dev Disabil Res Rev. 2000;6(3):214-9. Review.

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

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.

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.

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

Responsible Party:	Leigh Beglinger, Ph.D., University of Iowa
ClinicalTrials.gov Identifier:	NCT00368849 History of Changes
Other Study ID Numbers:	200508775
Study First Received:	August 24, 2006
Last Updated:	February 8, 2010
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Iowa:

Huntington Disease
Chorea
Attention
ADHD

ADD
Strattera
Atomoxetine

Additional relevant MeSH terms:

Chorea
Huntington Disease
Dyskinesias
Movement Disorders
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Basal Ganglia Diseases
Brain Diseases
Dementia
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases

Genetic Diseases, Inborn
Cognition Disorders
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Atomoxetine
Adrenergic Uptake Inhibitors
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Neurotransmitter Uptake Inhibitors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on February 09, 2012