Huntington DiseasePhase 2CIT-HDNCT00271596
Citalopram to Enhance Cognition in HD
A Phase 2 study testing 20mg daily citalopram in people with Huntington Disease and Chorea, run by University of Iowa at 3 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Huntington Disease, Chorea, Executive Dysfunction
- What is being tested?
- 20mg daily citalopram
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 33 participants
- Where
- 3 sitesUnited States
- Study dates
- Nov 2005to Nov 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
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- 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
Trial locations and contacts
3 sites in 1 country.
United States3 sites
The University of Iowa
Iowa City, Iowa, 52242
University of Rochester
Rochester, New York, 14618
Mayo Clinic Arizona
Scottsdale, Arizona, 85259
About this study
Official title: 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:
- 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.
Read the 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, 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, 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 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
- Huntington Disease, Chorea, Executive Dysfunction
- Being tested
- 20mg daily citalopram, Placebo
- Keywords
- Huntington Disease, Citalopram, Celexa, Chorea, Focus, ADD, ADHD, HD, SSRI
- Medical subject headings
- Huntington Disease, Chorea, Attention Deficit Disorder with Hyperactivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
20mg daily citalopramDrug
Also called Celexa
a selective serotonin reuptake inhibitor (SSRI) treatment administered over 16 weeks
PlaceboDrug
Also called Matching daily placebo
a daily matching placebo administered over 16 weeks
| Study group | Role | What they receive |
|---|---|---|
| Citalopram | Experimental | 20mg daily citalopram Receives: Drug: 20mg daily citalopram |
| Placebo | Placebo comparator | Matching daily placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Executive Function Composite Score Comparing Visit 2 (Week 0) to Visits 5 (Week 12) & 6 (Week 15) for the Citalopram Cohort Versus Placebo Cohort.
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.
Measured: after 15 weeks of treatment
Secondary outcomes (9)
Letter Number Sequencing Score Comparing Visit 2 (Week 0) to Visits 5 (Week 12) & 6 (Week 15) for the Citalopram Cohort Versus Placebo Cohort
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.
Measured: after 15 weeks of treatment
Semantic Fluency Score Comparing Visit 2 (Week 0) to Visits 5 (Week 12) & 6 (Week 15) for the Citalopram Cohort Versus Placebo Cohort
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.
Measured: after 15 weeks of treatment
Symbol-Digit Modalities Score Comparing Visit 2 (Week 0) to Visits 5 (Week 12) & 6 (Week 15) for the Citalopram Cohort Versus Placebo Cohort
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.
Measured: after 15 weeks of treatment
Verbal Fluency Score Comparing Visit 2 (Week 0) to Visits 5 (Week 12) & 6 (Week 15) for the Citalopram Cohort Versus Placebo Cohort
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.
Measured: after 15 weeks of treatment
Stroop Interference Score Comparing Visit 2 (Week 0) to Visits 5 (Week 12) & 6 (Week 15) for the Citalopram Cohort Versus Placebo Cohort
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.
Measured: after 15 weeks of treatment
Trails B Score Comparing Visit 2 (Week 0) to Visits 5 (Week 12) & 6 (Week 15) for the Citalopram Cohort Versus Placebo Cohort
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.
Measured: after 15 weeks of treatment
Hamilton Rating Scale for Depression Comparing Screening (Intake Visit) to Visit 6 (Week 15) for the Citalopram Cohort Versus Placebo Cohort
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.
Measured: after 15 weeks of treatment
Total Functional Capacity Score Comparing Baseline (Week -4) to Visits 4 (Week 6) & 6 (Week 15) for the Citalopram Cohort Versus Placebo Cohort
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.
Measured: after 15 weeks of treatment
Subgroup Analysis of the Hamilton Depression Rating Scale Comparing Screening (Intake Visit) to Visit 6 (Week 15) for the Citalopram Cohort Versus Placebo Cohort
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.
Measured: after 15 weeks of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jan 2006 (estimated)
- Study startNov 2005
- Primary completionApr 2011
- Study completionNov 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (20)Papers the sponsor has linked to this study.
- Other trials for Huntington DiseaseStudies of the same condition, open and under way.
- More trials run by University of IowaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Iowa
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS), Cure Huntington's Disease Initiative (CHDI), University of Rochester, Mayo Clinic
- Responsible party
- Principal investigator, Jess G. Fiedorowicz, University of Iowa
- Investigators
- Leigh J Beglinger, Ph.D., Principal investigator, The University of Iowa Psychiatry DepartmentJess G Fiedorowicz, M.D., Ph.D., Principal investigator, University of Iowa Psychiatry DepartmentKevin Biglan, M.D., M.P.H., Principal investigator, University of RochesterJohn Caviness, M.D., Principal investigator, Mayo ClinicRicardo Jorge, M.D., Principal investigator, University of Iowa Psychiatry Department
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00271596
- Sponsor's protocol ID
- 200509746
- Other IDs
- 5K23NS055733, A-2063
- Acronym
- CIT-HD
- Status last verified
- Feb 2013
- First submitted
- 30 Dec 2005
- Last updated
- 13 Mar 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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. doi: 10.1212/wnl.50.1.252.
PubMed 9443488Bauer 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. doi: 10.1111/j.1471-4159.2005.03169.x.
PubMed 16033418Bonelli 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.
PubMed 15076012Como 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. doi: 10.1002/mds.870120319.
PubMed 9159735Duan 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. doi: 10.1002/ana.20075.
PubMed 15048901Fennema-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.
PubMed 15452288Kish 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. doi: 10.1002/ana.410220318.
PubMed 2445259Menza 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.
PubMed 15377738Murman 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.
PubMed 9222184Naarding 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. doi: 10.1016/s0924-9338(01)00604-6.
PubMed 11777733Patel 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. doi: 10.3109/10401239609149087.
PubMed 8743645Ranen 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. doi: 10.1176/jnp.8.3.338.
PubMed 8854307Reynolds 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.
PubMed 10098889Reynolds 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.
PubMed 2442679Rosas 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.
PubMed 12771251
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Placebo-Controlled Pilot Study in Huntington's Disease (CIT-HD)
- ClinicalTrials.gov ID
- NCT00271596
- Acronym / sponsor ID
- CIT-HD / 200509746
- Conditions
- Huntington Disease, Chorea, Executive Dysfunction
- Keywords
- Huntington Disease, Citalopram, Celexa, Chorea, Focus, ADD, ADHD, HD
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- University of IowaUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS), Cure Huntington's Disease Initiative (CHDI), University of Rochester, Mayo Clinic
- Study start
- Nov 2005
- Primary completion
- Apr 2011 (actual)
- Study completion
- Nov 2011 (actual)
- First posted
- 2 Jan 2006 (estimated)
- Results
- Posted 13 Mar 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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, 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, 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 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Citalopram | Experimental | Drug: 20mg daily citalopram20mg daily citalopram |
| Placebo | Placebo comparator | Drug: PlaceboMatching daily placebo |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 20mg daily citalopramAlso: Celexaa selective serotonin reuptake inhibitor (SSRI) treatment administered over 16 weeks | Drug | Citalopram |
| PlaceboAlso: Matching daily placeboa daily matching placebo administered over 16 weeks | Drug | Placebo |
Primary outcome
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
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.
9 secondary outcomes
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
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
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
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
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
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
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
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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 9443488Aylward 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. doi: 10.1212/wnl.50.1.252.
- Background: PubMed 16033418Bauer 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. doi: 10.1111/j.1471-4159.2005.03169.x.
- Background: PubMed 15076012Bonelli 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.
- Background: PubMed 9159735Como 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. doi: 10.1002/mds.870120319.
- Background: PubMed 15048901Duan 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. doi: 10.1002/ana.20075.
- Background: PubMed 15452288Fennema-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.
- Background: PubMed 2445259Kish 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. doi: 10.1002/ana.410220318.
- Background: PubMed 15377738Menza 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.
- Background: PubMed 9222184Murman 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.
- Background: PubMed 11777733Naarding 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. doi: 10.1016/s0924-9338(01)00604-6.
- Background: PubMed 8743645Patel 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. doi: 10.3109/10401239609149087.
- Background: PubMed 8854307Ranen 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. doi: 10.1176/jnp.8.3.338.
- The University of Iowa's Huntington's Disease Center of ExcellenceLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Leigh J Beglinger, Ph.D. principal investigator
The University of Iowa Psychiatry Department
Jess G Fiedorowicz, M.D., Ph.D. principal investigator
University of Iowa Psychiatry Department
Kevin Biglan, M.D., M.P.H. principal investigator
University of Rochester
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 20mg daily citalopram in people with Huntington Disease and Chorea, run by University of Iowa at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Mar 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Mar 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00271596, which also lists 20 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Mar 2013.