CIT-HD: Study in Huntington's Disease

Condition(s) targeted: Huntington Disease; Chorea

Intervention: 20mg qd citalopram or placebo (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: University of Iowa

Official(s) and/or principal investigator(s):
Leigh J Beglinger, Ph.D., Principal Investigator, Affiliation: The University of Iowa Psychiatry Department
Jess G Fiedorowicz, M.D., M.S., Principal Investigator, Affiliation: University of Iowa Psychiatry Department

Overall contact:
William H Adams, BA, Phone: 319-353-4411, Email: William-H-Adams@uiowa.edu

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) in the neostriatum among patients with recently diagnosed Huntington's disease.

Official title: A Randomized, Placebo-Controlled Pilot Study in Huntington's Disease (CIT-HD)

Study design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Efficacy Study

Primary outcome: 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

Detailed description: 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) in the neostriatum among patients with recently diagnosed Huntington's Disease.

Main Hypotheses:

1. 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.

2. Performance on measures of executive function will be significantly associated with measures of functional status.

3. 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.

4. 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.

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Diagnosis of HD, confirmed by genetic testing and the presence of unequivocal motor

signs of HD (e. g., chorea) in combination with a positive family history of HD

- Aged between 18 and 65

- Ability to provide written informed consent

- Mild stage HD (Shoulson and Fahn Scale Stage 1 or 2)

- Mild executive dysfunction: participants will be given the Wide Range Achievement

Test-4 (WRAT-4) Reading Subtest as a measure of estimated verbal IQ, as well as the UHDRS Cognitive Scale tests (Stroop Test, Verbal Fluency, and Symbol Digit Modalities Test). Patients will be included if they score at least 1 standard deviation below their WRAT-4 estimated cognitive level using age and education-corrected norms for the cognitive tests on at least 2 out of 3 of the UHDRS cognitive tests.

Exclusion Criteria:

- Age greater than 65

- Current major depression as defined by the Mood Module of the Structured Clinical

Interview for DSM-IV-TR Axis I Disorders during psychiatric exam 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, as assessed by the study psychiatrist during the interview and exam.

- Current use of an SSRI or other treatment for depression (e. g., use of an MAOI) or

treatment with an SSRI within the past two months.

- 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 with loss of consciousness > 5 minutes; 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.

William H Adams, BA, Phone: 319-353-4411, Email: William-H-Adams@uiowa.edu

The University of Iowa, Iowa City, Iowa 52242, United States; Recruiting
William H Adams, BA, Phone: 319-353-4411, Email: William-H-Adams@uiowa.edu
Nicole R Ramza, BA, Phone: 319-384-9408, Email: Nicole-Ramza@uiowa.edu
Leigh J Beglinger, Ph.D., Principal Investigator
Jess G Fiedorowicz, M.D., M.S., Sub-Investigator

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

Related 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.

Starting date: November 2005
Ending date: March 2012
Last updated: September 5, 2008