CIT-HD: Study in Huntington's Disease - Full Text View

Sponsor:	University of Iowa
Collaborators:	National Institute of Neurological Disorders and Stroke (NINDS) Cure Huntington's Disease Initiative (CHDI)
Information provided by (Responsible Party):	Jess G. Fiedorowicz, University of Iowa
ClinicalTrials.gov Identifier:	NCT00271596

Purpose

This research plan proposes to conduct a double-blind, placebo-controlled pilot clinical trial in 36 adults with mild Huntington's disease (HD) to address the following research aims:

To determine the effect of citalopram compared to placebo in patients with early HD on executive function and other outcome variables including functional measures (health-related quality of life, work productivity, and self-reported attention), motor performance, and psychiatric status,
To study the relationship between executive function and functional status in patients with early HD after selective serotonin reuptake inhibitor (SSRI) treatment, and
To examine the effect of citalopram treatment on volumetric and metabolic (i.e, N-acetyl-aspartate concentration) measures in the neostriatum among patients with recently diagnosed Huntington's disease.

Condition	Intervention	Phase
Huntington Disease Chorea Attention Executive Dysfunction	Drug: 20mg qd citalopram or placebo	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	A Randomized, Placebo-Controlled Pilot Study in Huntington's Disease (CIT-HD)

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: Serotonin Benzetimide Dexetimide Citalopram hydrobromide Citalopram Escitalopram Escitalopram oxalate

U.S. FDA Resources

Further study details as provided by University of Iowa:

Primary Outcome Measures:

executive function and other outcome variables including functional measures (health-related quality of life, work productivity, and self-reported attention), motor performance, and psychiatric status [ Time Frame: after 16 weeks of treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

volumetric and metabolic (i.e., N-Acetyl-Aspartate concentration) neuroimaging measures in the neostriatum [ Time Frame: after 16 weeks of treatment ] [ Designated as safety issue: No ]
serotonin transporter gene polymorphism (5HTTLPR) and cognitive treatment response to an SSRI [ Time Frame: after 16 weeks of treatment ] [ Designated as safety issue: No ]

Estimated Enrollment:	36
Study Start Date:	November 2005
Estimated Study Completion Date:	March 2012
Estimated Primary Completion Date:	March 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 20mg qd citalopram or placebo	Drug: 20mg qd citalopram or placebo a selective serotonin reuptake inhibitor (SSRI) treatment administered over 16 weeks Other Name: Celexa

Detailed Description:

Specific Aims:

To examine the effects of sixteen weeks of treatment with the selective serotonin reuptake inhibitor (SSRI) citalopram compared to placebo on executive function in patients with early Huntington's disease (HD).
To study the relationship between executive function and functional status in patients with early HD after SSRI treatment.
To determine the effect of sixteen weeks of citalopram compared to placebo on other outcome variables including functional measures (health-related quality of life, work productivity, and self-reported attention), motor performance, and psychiatric status.
To examine the effect of citalopram treatment on volumetric and metabolic (i.e, N-Acetyl-Aspartate concentration) measures in the neostriatum among patients with recently diagnosed Huntington's Disease.

Main Hypotheses:

At the end of the treatment protocol (i.e., sixteen weeks), patients receiving citalopram as compared with placebo will show a significantly greater improvement on tests of executive function.
Performance on measures of executive function will be significantly associated with measures of functional status.
At the end of the treatment protocol (i.e., sixteen weeks), patients receiving citalopram as compared with placebo will show a significantly greater improvement in functional status and psychiatric ratings; motor score is not expected to change as a result of citalopram therapy.
Using structural MRI and 1H-MRS, after 16 weeks of citalopram treatment, patients with recently diagnosed Huntington's Disease will show greater changes from baseline on volumetric and metabolic (i.e., N-Acetyl-Aspartate concentration) neuroimaging measures in the neostriatum than those on placebo.

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Gene positive HD test (or, if untested, an HD diagnosis) with some abnormal motor signs (i.e., diagnostic confidence level of greater than or equal to 1 as measured by the UHDRS).
Aged between 18 and 75
Ability to provide written informed consent
Mild stage HD (Shoulson and Fahn Scale Stage 1 or 2)
Mild executive dysfunction: Participants must have complaints of poor cognition, mild functional decline, or demonstrate objective evidence of decline from their premorbid level
Participants are able to complete all study assessments

Exclusion Criteria:

Age under 18 or greater than 75
Current major depression deemed significant by the investigator at the screening visit or current suicidal ideation.
Any unstable or severe psychiatric disease including DSM-IV-TR diagnoses of schizophrenia, bipolar affective disorder, dementia, delirium, severe anxiety and/or substance abuse/dependence.
Current use of an SSRI or other treatment for depression (e.g., use of an MAOI) or treatment with an SSRI within the past 14 days.
Current use of St. John's wort within the past 14 days.
To ensure performance on cognitive measures are not affected by specific concomitant medications, participants taking methylphenidate, amphetamine/dextroamphetamine, atomoxetine, an acetyl cholinesterase inhibitor, an atypical antipsychotic, kava kava, Ginkgo Biloba, or an anxiolytic drug may be excluded unless their dose and dosing frequency have remained stable for 30 days prior to receiving study drug. Continued participation also requires the dose and dosing frequency remain stable throughout the study.
Patients who are pregnant, nursing, or planning to become pregnant during the study.
Patients who are unable to participate in the study assessments (cognitive, functional, psychiatric and motor scales) due to cognitive, motor, or sensory impairments (i.e., significant vision or hearing deficits).
Other serious medical conditions such as cardiovascular or cerebrovascular disease; head injury deemed clinically significant by the PI; neurological disorder or insult other than HD.
Learning disability or other medical condition that is likely to affect cognitive function; history of symptoms indicative of attention deficit hyperactivity disorder (ADHD) in childhood; or a diagnosis of ADHD.

It is important to note that participants who are unable to receive an MRI scan may still participate in this study

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00271596

Locations

United States, Arizona
Mayo Clinic Arizona
Scottsdale, Arizona, United States, 85259
United States, Iowa
The University of Iowa
Iowa City, Iowa, United States, 52242
United States, New York
University of Rochester
Rochester, New York, United States, 14618

Sponsors and Collaborators

University of Iowa

National Institute of Neurological Disorders and Stroke (NINDS)

Cure Huntington's Disease Initiative (CHDI)

Investigators

Principal Investigator:	Leigh J Beglinger, Ph.D.	The University of Iowa Psychiatry Department
Principal Investigator:	Jess G Fiedorowicz, M.D., Ph.D.	University of Iowa Psychiatry Department
Principal Investigator:	Kevin Biglan, M.D., M.P.H.	University of Rochester
Principal Investigator:	John Caviness, M.D.	Mayo Clinic
Principal Investigator:	Ricardo Jorge, M.D.	University of Iowa Psychiatry Department

More Information

Additional Information:

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

Publications:

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.

Bauer A, Zilles K, Matusch A, Holzmann C, Riess O, von Horsten S. Regional and subtype selective changes of neurotransmitter receptor density in a rat transgenic for the Huntington's disease mutation. J Neurochem. 2005 Aug;94(3):639-50. Erratum in: J Neurochem. 2005 Aug;94(4):1167.

Bonelli RM, Wenning GK, Kapfhammer HP. Huntington's disease: present treatments and future therapeutic modalities. Int Clin Psychopharmacol. 2004 Mar;19(2):51-62. Review.

Como PG, Rubin AJ, O'Brien CF, Lawler K, Hickey C, Rubin AE, Henderson R, McDermott MP, McDermott M, Steinberg K, Shoulson I. A controlled trial of fluoxetine in nondepressed patients with Huntington's disease. Mov Disord. 1997 May;12(3):397-401.

Duan W, Guo Z, Jiang H, Ladenheim B, Xu X, Cadet JL, Mattson MP. Paroxetine retards disease onset and progression in Huntingtin mutant mice. Ann Neurol. 2004 Apr;55(4):590-4.

Fennema-Notestine C, Archibald SL, Jacobson MW, Corey-Bloom J, Paulsen JS, Peavy GM, Gamst AC, Hamilton JM, Salmon DP, Jernigan TL. In vivo evidence of cerebellar atrophy and cerebral white matter loss in Huntington disease. Neurology. 2004 Sep 28;63(6):989-95.

Kish SJ, Shannak K, Hornykiewicz O. Elevated serotonin and reduced dopamine in subregionally divided Huntington's disease striatum. Ann Neurol. 1987 Sep;22(3):386-9.

Menza M, Marin H, Kaufman K, Mark M, Lauritano M. Citalopram treatment of depression in Parkinson's disease: the impact on anxiety, disability, and cognition. J Neuropsychiatry Clin Neurosci. 2004 Summer;16(3):315-9.

Murman DL, Giordani B, Mellow AM, Johanns JR, Little RJ, Hariharan M, Foster NL. Cognitive, behavioral, and motor effects of the NMDA antagonist ketamine in Huntington's disease. Neurology. 1997 Jul;49(1):153-61.

Naarding P, Kremer HP, Zitman FG. Huntington's disease: a review of the literature on prevalence and treatment of neuropsychiatric phenomena. Eur Psychiatry. 2001 Dec;16(8):439-45. Review.

Patel SV, Tariot PN, Asnis J. L-Deprenyl augmentation of fluoxetine in a patient with Huntington's disease. Ann Clin Psychiatry. 1996 Mar;8(1):23-6.

Ranen NG, Lipsey JR, Treisman G, Ross CA. Sertraline in the treatment of severe aggressiveness in Huntington's disease. J Neuropsychiatry Clin Neurosci. 1996 Summer;8(3):338-40.

Reynolds GP, Dalton CF, Tillery CL, Mangiarini L, Davies SW, Bates GP. Brain neurotransmitter deficits in mice transgenic for the Huntington's disease mutation. J Neurochem. 1999 Apr;72(4):1773-6.

Reynolds GP, Pearson SJ. Decreased glutamic acid and increased 5-hydroxytryptamine in Huntington's disease brain. Neurosci Lett. 1987 Jul 22;78(2):233-8.

Rosas HD, Koroshetz WJ, Chen YI, Skeuse C, Vangel M, Cudkowicz ME, Caplan K, Marek K, Seidman LJ, Makris N, Jenkins BG, Goldstein JM. Evidence for more widespread cerebral pathology in early HD: an MRI-based morphometric analysis. Neurology. 2003 May 27;60(10):1615-20.

Shoulson I, Goldblatt D, Charlton M, Joynt RJ. Huntington's disease: treatment with muscimol, a GABA-mimetic drug. Ann Neurol. 1978 Sep;4(3):279-84.

Yohrling IV GJ, Jiang GC, DeJohn MM, Robertson DJ, Vrana KE, Cha JH. Inhibition of tryptophan hydroxylase activity and decreased 5-HT1A receptor binding in a mouse model of Huntington's disease. J Neurochem. 2002 Sep;82(6):1416-23.

Responsible Party:	Jess G. Fiedorowicz, Assistant Professor, University of Iowa
ClinicalTrials.gov Identifier:	NCT00271596 History of Changes
Other Study ID Numbers:	200509746, 5K23NS055733
Study First Received:	December 30, 2005
Last Updated:	January 16, 2012
Health Authority:	United States: Federal Government

Keywords provided by University of Iowa:

Huntington Disease
Citalopram
Celexa
Chorea
Attention

Focus
ADD
ADHD
HD
SSRI

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
Citalopram
Serotonin Uptake Inhibitors
Dexetimide
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Serotonin Agents

ClinicalTrials.gov processed this record on February 12, 2012