Citalopram to Enhance Cognition in HD

NCT ID: NCT00271596

Last Updated: 2013-03-13

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

33 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-11-30

Study Completion Date

2011-11-30

Brief Summary

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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:

1. 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,
2. To study the relationship between executive function and functional status in patients with early HD after selective serotonin reuptake inhibitor (SSRI) treatment, and
3. 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.

Detailed Description

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Specific Aims:

1. 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).
2. To study the relationship between executive function and functional status in patients with early HD after SSRI treatment.
3. 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.
4. 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:

1. At the end of the treatment protocol, patients receiving citalopram as compared with placebo will show a significantly greater improvement on tests of executive function.
2. Performance on measures of executive function will be significantly associated with measures of functional status.
3. At the end of the treatment protocol, 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.
4. Using structural MRI and occipital proton magnetic resonance spectroscopy (1H-MRS), after 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.

Conditions

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Huntington Disease Chorea Executive Dysfunction

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Citalopram

20mg daily citalopram

Group Type EXPERIMENTAL

20mg daily citalopram

Intervention Type DRUG

a selective serotonin reuptake inhibitor (SSRI) treatment administered over 16 weeks

Placebo

Matching daily placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

a daily matching placebo administered over 16 weeks

Interventions

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20mg daily citalopram

a selective serotonin reuptake inhibitor (SSRI) treatment administered over 16 weeks

Intervention Type DRUG

Placebo

a daily matching placebo administered over 16 weeks

Intervention Type DRUG

Other Intervention Names

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Celexa Matching daily placebo

Eligibility Criteria

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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 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role collaborator

Cure Huntington's Disease Initiative (CHDI)

UNKNOWN

Sponsor Role collaborator

University of Rochester

OTHER

Sponsor Role collaborator

Mayo Clinic

OTHER

Sponsor Role collaborator

University of Iowa

OTHER

Sponsor Role lead

Responsible Party

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Jess G. Fiedorowicz

Assistant Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Leigh J Beglinger, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

The University of Iowa Psychiatry Department

Jess G Fiedorowicz, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

University of Iowa Psychiatry Department

Kevin Biglan, M.D., M.P.H.

Role: PRINCIPAL_INVESTIGATOR

University of Rochester

John Caviness, M.D.

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Ricardo Jorge, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Iowa Psychiatry Department

Locations

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Mayo Clinic Arizona

Scottsdale, Arizona, United States

Site Status

The University of Iowa

Iowa City, Iowa, United States

Site Status

University of Rochester

Rochester, New York, United States

Site Status

Countries

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United States

References

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Bonelli RM, Wenning GK, Kapfhammer HP. Huntington's disease: present treatments and future therapeutic modalities. Int Clin Psychopharmacol. 2004 Mar;19(2):51-62. doi: 10.1097/00004850-200403000-00001.

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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. doi: 10.1212/01.wnl.0000138434.68093.67.

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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. doi: 10.1176/jnp.16.3.315.

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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. doi: 10.1212/wnl.49.1.153.

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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. doi: 10.1046/j.1471-4159.1999.721773.x.

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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. doi: 10.1016/0304-3940(87)90639-2.

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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. doi: 10.1212/01.wnl.0000065888.88988.6e.

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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. doi: 10.1002/ana.410040316.

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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. doi: 10.1046/j.1471-4159.2002.01084.x.

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Beglinger LJ, Adams WH, Fiedorowicz JG, Duff K, Langbehn D, Biglan K, Caviness J, Olson B, Paulsen JS. Practice Effects and Stability of Neuropsychological and UHDRS Tests Over Short Retest Intervals in Huntington Disease. J Huntingtons Dis. 2015;4(3):251-60. doi: 10.3233/JHD-150159.

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Beglinger LJ, Adams WH, Langbehn D, Fiedorowicz JG, Caviness J, Biglan K, Olson B, Paulsen JS. Does interval between screening and baseline matter in HD cognitive clinical trials? J Huntingtons Dis. 2014;3(2):139-44. doi: 10.3233/JHD-140100.

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Beglinger LJ, Adams WH, Langbehn D, Fiedorowicz JG, Jorge R, Biglan K, Caviness J, Olson B, Robinson RG, Kieburtz K, Paulsen JS. Results of the citalopram to enhance cognition in Huntington disease trial. Mov Disord. 2014 Mar;29(3):401-5. doi: 10.1002/mds.25750. Epub 2013 Dec 27.

Reference Type DERIVED
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Related Links

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http://www.uihealthcare.com/depts/huntingtonsdisease/index.html

The University of Iowa's Huntington's Disease Center of Excellence

Other Identifiers

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5K23NS055733

Identifier Type: NIH

Identifier Source: secondary_id

View Link

A-2063

Identifier Type: OTHER

Identifier Source: secondary_id

200509746

Identifier Type: -

Identifier Source: org_study_id

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