Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Citalopram to Enhance Cognition in HD (CIT-HD)

This study has been completed.
Sponsor:
Collaborators:
Cure Huntington's Disease Initiative (CHDI)
University of Rochester
Mayo Clinic
Information provided by (Responsible Party):
Jess G. Fiedorowicz, University of Iowa
ClinicalTrials.gov Identifier:
NCT00271596
First received: December 30, 2005
Last updated: February 8, 2013
Last verified: February 2013

December 30, 2005
February 8, 2013
November 2005
April 2011   (final data collection date for primary outcome measure)
Executive Function Composite Score Comparing Visit 2 (Week 0) to Visits 5 (Week 12) & 6 (Week 15) for the Citalopram Cohort Versus Placebo Cohort. [ Time Frame: after 15 weeks of treatment ] [ Designated as safety issue: No ]
Full Scale Name: The Executive Composite Score (ECS). Definition: Subscales were averaged to compute this composite total score. The ECS is the weighted average of performance on 6 subtests of executive function, including (1) the Controlled Oral Word Association Test, (2) Symbol Digit Modalities test; (3) Stroop Color Word Test (Interference Trial), (4) Trail Making test (Part B), (5) Letter-Number Sequencing, and (6) Animal Naming. Construct Measured: Thinking tasks involving planning, working memory, attention, problem solving, verbal reasoning, inhibition, mental flexibility, and task switching. ECS Scale Range: The ECS score ranges from -5 to +5 on a standardized (Z) score scale, where lower scores indicate poorer performance on executive functioning tasks. Change Calculation Details: Compares change in executive functioning performance from visit 2 (week 0) to the weighted average of visits 5 (week 12) & 6 (week 15) for the citalopram versus placebo cohort.
  • 1) The primary outcome measure will be an executive function comparison
  • 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., six weeks), patients receiving citalopram as compared with placebo will show a significantly greater improvement in functional status and psychiatric ratings.
Complete list of historical versions of study NCT00271596 on ClinicalTrials.gov Archive Site
  • Letter Number Sequencing Score Comparing Visit 2 (Week 0) to Visits 5 (Week 12) & 6 (Week 15) for the Citalopram Cohort Versus Placebo Cohort [ Time Frame: after 15 weeks of treatment ] [ Designated as safety issue: No ]
    Full Scale Name: Letter Number Sequencing (LNS) subtest from the Wechsler Adult Intelligence Scale (WAIS) third edition. Definition: LNS is a task that requires the reordering of an initially unordered set of letters and numbers. Construct Measured: Working memory. LNS Score Range: Raw scores may range from 0 to 21, where lower scores indicate poorer performance in working memory. Change Calculation Details: Compares change in working memory performance from visit 2 (week 0) to the weighted average of visits 5 (week 12) & 6 (week 15) for the citalopram versus placebo cohort.
  • Semantic Fluency Score Comparing Visit 2 (Week 0) to Visits 5 (Week 12) & 6 (Week 15) for the Citalopram Cohort Versus Placebo Cohort [ Time Frame: after 15 weeks of treatment ] [ Designated as safety issue: No ]
    Semantic Fluency Score. Definition: The Semantic Fluency Score is the number of words a person can produce given a category, including naming (1) Animal names, (2) Fruit names, (3) Boy names, (4) Girl names, and (5) Vegetable names. Construct Measured: Working memory and verbal initiation. Scale Range: The Semantic Fluency Score ranges from -5 to +5 on a standardized (Z) score scale, where lower scores indicate poorer performance on working memory tasks. Change Calculation Details: Compares change in working memory performance from visit 2 (week 0) where patients named fruit names to the weighted average of visits 5 (week 12) & 6 (week 15) where patients named girl names and vegetable names respectively for the citalopram versus placebo cohort.
  • Symbol-Digit Modalities Score Comparing Visit 2 (Week 0) to Visits 5 (Week 12) & 6 (Week 15) for the Citalopram Cohort Versus Placebo Cohort [ Time Frame: after 15 weeks of treatment ] [ Designated as safety issue: No ]
    Full Scale Name: The Symbol Digit Modalities Test (SDMT). Definition: The SDMT screens for organic cerebral dysfunction by having the examinee use a reference key to pair specific numbers with given geometric figures in 90 seconds. Construct Measured: Attention, processing speed, and working memory. SDMT Scale Range: Raw scores may range from 0 to 110, where lower scores indicate poorer performance. Change Calculation Details: Compares change in performance from visit 2 (week 0) to the weighted average of visits 5 (week 12) & 6 (week 15) for the citalopram versus placebo cohort.
  • Verbal Fluency Score Comparing Visit 2 (Week 0) to Visits 5 (Week 12) & 6 (Week 15) for the Citalopram Cohort Versus Placebo Cohort [ Time Frame: after 15 weeks of treatment ] [ Designated as safety issue: No ]
    Full Scale Name: The Verbal Fluency Score (VFC). Definition: The VFC is the number of words a person can produce given a letter, including (1) Naming words that start with F, A, and S; (2) naming words that start with K, W, and R; (3) naming words that start with V, I, and P; (4) naming words that start with O, G, and B; (5) naming words that start with E, N, and T; and (6) naming words that start with J, C, and S. Construct Measured: Verbal initiation and flexibility. Scale Range: The Verbal Fluency Composite Score ranges from -5 to +5 on a standardized (Z) score scale, where lower scores indicate poorer performance. Change Calculation Details: Compares change in verbal initiation and flexibility from visit 2 (week 0) where patients named words starting with O, G, and B to the weighted average of visits 5 (week 12) and 6 (week 15) where patients named words starting with E, N, and T, and J, C, and S respectively for the citalopram versus placebo cohort.
  • Stroop Interference Score Comparing Visit 2 (Week 0) to Visits 5 (Week 12) & 6 (Week 15) for the Citalopram Cohort Versus Placebo Cohort [ Time Frame: after 15 weeks of treatment ] [ Designated as safety issue: No ]
    Full Scale Name: Stroop Interference subtest from The Stroop Color and Word Test. Definition: Participants are asked to name the ink color in which a word is printed when the word itself (which is irrelevant to the task) is the name of a different color rather than the same color. For example, participants may be asked to say "red" to the word blue printed in red ink. Constructs Measured: Selective attention, response inhibition, cognitive flexibility, and processing speed. Scale Range: The Stroop Interference score ranges from -5 to +5 on a standardized (Z) score scale, where lower scores indicate poorer performance. Change Calculation Details: Compares change in attention and processing speed performance from visit 2 (week 0) to the weighted average of visits 5 (week 12) and 6 (week 15) for the citalopram versus placebo cohort.
  • Trails B Score Comparing Visit 2 (Week 0) to Visits 5 (Week 12) & 6 (Week 15) for the Citalopram Cohort Versus Placebo Cohort [ Time Frame: after 15 weeks of treatment ] [ Designated as safety issue: No ]
    Full Scale Name: Trail Making Test Part B (TMT-B). Definition: The TMT-B test requires participants to "connect-the-dots" of 25 consecutive targets on a sheet of paper where the subject alternates between numbers and letters, going in both numerical and alphabetical order. Constructs Measured: Attention, set shifting, and processing speed. Scale range: The TMT-B score ranges from -5 to +5 on a standardized (Z) score scale, where lower scores indicate poorer performance. Change Calculation Details: Compares change in attention and processing speed performance from visit 2 (week 0) to the weighted average of visits 5 (week 12) and 6 (week 15) for the citalopram versus placebo cohort.
  • Hamilton Rating Scale for Depression Comparing Screening (Intake Visit) to Visit 6 (Week 15) for the Citalopram Cohort Versus Placebo Cohort [ Time Frame: after 15 weeks of treatment ] [ Designated as safety issue: No ]
    Full Scale Name: Hamilton Rating Scale for Depression (HAM-D). Definition: The Hamilton Rating Scale for Depression is a clinician-administered multiple item questionnaire used to provide an indication of depression. Construct Measured: Depression. HAM-D Score Range: Raw scores may range from 0 to 54, where higher scores indicate worsening mood. Change Calculation Details: Compares change in mood from screening (intake visit) to visit 6 (week 15) for the citalopram versus placebo cohort.
  • Total Functional Capacity Score Comparing Baseline (Week -4) to Visits 4 (Week 6) & 6 (Week 15) for the Citalopram Cohort Versus Placebo Cohort [ Time Frame: after 15 weeks of treatment ] [ Designated as safety issue: No ]
    Full Scale Name: The Total Functional Capacity (TFC) subscale from the Unified Huntington's Disease Rating Scale (UHDRS). Definition: The TFC is a score that classifies five stages of Huntington's Disease and five levels of function in the domains of workplace, finances, domestic chores, activities of daily living and requirements for unskilled or skilled care. Construct Measured: Activities of Daily Living. Scale Range: The TFC score ranges from 0 to 13, where lower scores indicate poorer performance in activities of daily living. Change Calculation Details: Compares change in TFC performance from Baseline (week -4) to the weighted average of visits 4 (week 6) and 6 (week 15) for the citalopram versus placebo cohort.
  • Subgroup Analysis of the Hamilton Depression Rating Scale Comparing Screening (Intake Visit) to Visit 6 (Week 15) for the Citalopram Cohort Versus Placebo Cohort [ Time Frame: after 15 weeks of treatment ] [ Designated as safety issue: No ]
    Full Scale Name: Hamilton Rating Scale for Depression (HAM-D). Definition: The Hamilton Rating Scale for Depression is a clinician-administered multiple item questionnaire used to provide an indication of depression. Construct Measured: Depression. HAM-D Score Range: Raw scores may range from 0 to 54, where higher scores indicate worsening mood. Change Calculation Details: This analysis was restricted to a subgroup and, accordingly, does not reflect the total number of participants as reported in the Participant Flow. This analysis compares change in mood from screening (intake visit) to visit 6 (week 15) for the citalopram versus placebo cohort.
Not Provided
Not Provided
Not Provided
 
Citalopram to Enhance Cognition in HD
A Randomized, Placebo-Controlled Pilot Study in Huntington's Disease (CIT-HD)

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.

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.
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
  • Huntington Disease
  • Chorea
  • Executive Dysfunction
  • Drug: 20mg daily citalopram
    a selective serotonin reuptake inhibitor (SSRI) treatment administered over 16 weeks
    Other Name: Celexa
  • Drug: Placebo
    a daily matching placebo administered over 16 weeks
    Other Name: Matching daily placebo
  • Experimental: Citalopram
    20mg daily citalopram
    Intervention: Drug: 20mg daily citalopram
  • Placebo Comparator: Placebo
    Matching daily placebo
    Intervention: Drug: Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
33
November 2011
April 2011   (final data collection date for primary outcome measure)

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

Both
18 Years to 75 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00271596
200509746, 5K23NS055733, A-2063
Yes
Jess G. Fiedorowicz, University of Iowa
University of Iowa
  • National Institute of Neurological Disorders and Stroke (NINDS)
  • Cure Huntington's Disease Initiative (CHDI)
  • University of Rochester
  • Mayo Clinic
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
University of Iowa
February 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP