Trial Outcomes & Findings for Citalopram to Enhance Cognition in HD (NCT NCT00271596)

NCT ID: NCT00271596

Last Updated: 2013-03-13

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 33 participants
• Primary outcome timeframe: after 15 weeks of treatment
• Results posted on: 2013-03-13

Participant Flow

Thirty-six individuals were screened and 33 participants were randomized between May 2007 and April 2011 Participants were recruited using advertisements, by speaking at HD events, through local clinics and through two HD registries: The University of Iowa HD registry and the National HD Research Roster (Indiana).

Following the baseline visit, participants completed a study visit (i.e., Visit 01) after 2 weeks in order to wash-out practice effects on primary outcome measures. To further control for practice effects, participants received placebo for 14 days prior to randomization (i.e., using a placebo run-in design).

Participant milestones

Measure	Citalopram 20mg daily citalopram	Placebo Matching daily placebo
Overall Study STARTED	17	16
Overall Study COMPLETED	16	15
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Measure	Citalopram 20mg daily citalopram	Placebo Matching daily placebo
Overall Study Protocol Violation	1	0
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Citalopram to Enhance Cognition in HD

Baseline characteristics by cohort

Measure	Citalopram n=17 Participants 20mg daily citalopram	Placebo n=16 Participants Matching daily placebo	Total n=33 Participants Total of all reporting groups
Age Continuous Age	47.33 years STANDARD_DEVIATION 14.61 • n=93 Participants	45.13 years STANDARD_DEVIATION 13.59 • n=4 Participants	46.2 years STANDARD_DEVIATION 13.9 • n=27 Participants
Sex: Female, Male Female	8 Participants n=93 Participants	7 Participants n=4 Participants	15 Participants n=27 Participants
Sex: Female, Male Male	9 Participants n=93 Participants	9 Participants n=4 Participants	18 Participants n=27 Participants

PRIMARY outcome

Timeframe: after 15 weeks of treatment

Population: Intention to treat analysis was performed using a mixed linear model controlling for practice effects comparing visit 2 (week 0) to the weighted average of visits 5 (week 12) \& 6 (week 15) for the citalopram 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.

Outcome measures

Measure	Citalopram n=16 Participants 20mg daily citalopram	Placebo n=15 Participants Matching daily placebo
Executive Function Composite Score Comparing Visit 2 (Week 0) to Visits 5 (Week 12) & 6 (Week 15) for the Citalopram Cohort Versus Placebo Cohort.	0.005 units on a scale Standard Error 0.067	0.172 units on a scale Standard Error 0.071

SECONDARY outcome

Timeframe: after 15 weeks of treatment

Population: Intention to treat analysis was performed using a mixed linear model controlling for practice effects comparing visit 2 (week 0) to the weighted average of visits 5 (week 12) \& 6 (week 15) for the citalopram 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.

Outcome measures

Measure	Citalopram n=16 Participants 20mg daily citalopram	Placebo n=15 Participants Matching daily placebo
Letter Number Sequencing Score Comparing Visit 2 (Week 0) to Visits 5 (Week 12) & 6 (Week 15) for the Citalopram Cohort Versus Placebo Cohort	-0.113 units on a scale Standard Error 0.113	0.225 units on a scale Standard Error 0.124

SECONDARY outcome

Timeframe: after 15 weeks of treatment

Population: Intention to treat analysis was performed using a mixed linear model controlling for practice effects comparing 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. 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.

Outcome measures

Measure	Citalopram n=16 Participants 20mg daily citalopram	Placebo n=15 Participants Matching daily placebo
Semantic Fluency Score Comparing Visit 2 (Week 0) to Visits 5 (Week 12) & 6 (Week 15) for the Citalopram Cohort Versus Placebo Cohort	0.386 units on a scale Standard Error 0.192	0.664 units on a scale Standard Error 0.187

SECONDARY outcome

Timeframe: after 15 weeks of treatment

Population: Intention to treat analysis was performed using a mixed linear model controlling for practice effects comparing visit 2 (week 0) to the weighted average of visits 5 (week 12) \& 6 (week 15) for the citalopram 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.

Outcome measures

Measure	Citalopram n=16 Participants 20mg daily citalopram	Placebo n=15 Participants Matching daily placebo
Symbol-Digit Modalities Score Comparing Visit 2 (Week 0) to Visits 5 (Week 12) & 6 (Week 15) for the Citalopram Cohort Versus Placebo Cohort	-0.227 units on a scale Standard Error 0.113	-0.170 units on a scale Standard Error 0.103

SECONDARY outcome

Timeframe: after 15 weeks of treatment

Population: Intention to treat analysis was performed using a mixed linear model controlling for practice effects comparing visit 2 (week 0) to the weighted average of visits 5 (week 12) \& 6 (week 15) for the citalopram 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.

Outcome measures

Measure	Citalopram n=16 Participants 20mg daily citalopram	Placebo n=15 Participants Matching daily placebo
Verbal Fluency Score Comparing Visit 2 (Week 0) to Visits 5 (Week 12) & 6 (Week 15) for the Citalopram Cohort Versus Placebo Cohort	0.140 units on a scale Standard Error 0.109	0.071 units on a scale Standard Error 0.103

SECONDARY outcome

Timeframe: after 15 weeks of treatment

Population: Intention to treat analysis was performed using a mixed linear model controlling for practice effects comparing visit 2 (week 0) to the weighted average of visits 5 (week 12) \& 6 (week 15) for the citalopram 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.

Outcome measures

Measure	Citalopram n=16 Participants 20mg daily citalopram	Placebo n=15 Participants Matching daily placebo
Stroop Interference Score Comparing Visit 2 (Week 0) to Visits 5 (Week 12) & 6 (Week 15) for the Citalopram Cohort Versus Placebo Cohort	-0.256 units on a scale Standard Error 0.122	-0.046 units on a scale Standard Error 0.123

SECONDARY outcome

Timeframe: after 15 weeks of treatment

Population: Intention to treat analysis was performed using a mixed linear model controlling for practice effects comparing visit 2 (week 0) to the weighted average of visits 5 (week 12) \& 6 (week 15) for the citalopram 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.

Outcome measures

Measure	Citalopram n=16 Participants 20mg daily citalopram	Placebo n=15 Participants Matching daily placebo
Trails B Score Comparing Visit 2 (Week 0) to Visits 5 (Week 12) & 6 (Week 15) for the Citalopram Cohort Versus Placebo Cohort	0.087 units on a scale Standard Error 0.273	0.405 units on a scale Standard Error 0.397

SECONDARY outcome

Timeframe: after 15 weeks of treatment

Population: Intention to treat analysis was performed using a mixed linear model comparing screening (intake visit) to Visit 6 (week 15) for the citalopram 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.

Outcome measures

Measure	Citalopram n=16 Participants 20mg daily citalopram	Placebo n=15 Participants Matching daily placebo
Hamilton Rating Scale for Depression Comparing Screening (Intake Visit) to Visit 6 (Week 15) for the Citalopram Cohort Versus Placebo Cohort	-0.67 units on a scale Standard Error 0.76	1.23 units on a scale Standard Error 0.89

SECONDARY outcome

Timeframe: after 15 weeks of treatment

Population: Intention to treat analysis was performed using a mixed linear model comparing baseline (week -4) to the weighted average of Visits 4 (week 6) \& 6 (week 15) for the citalopram 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.

Outcome measures

Measure	Citalopram n=16 Participants 20mg daily citalopram	Placebo n=15 Participants Matching daily placebo
Total Functional Capacity Score Comparing Baseline (Week -4) to Visits 4 (Week 6) & 6 (Week 15) for the Citalopram Cohort Versus Placebo Cohort	-0.54 units on a scale Standard Error 0.46	-0.06 units on a scale Standard Error 0.50

SECONDARY outcome

Timeframe: after 15 weeks of treatment

Population: 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.

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.

Outcome measures

Measure	Citalopram n=14 Participants 20mg daily citalopram	Placebo n=14 Participants Matching daily placebo
Subgroup Analysis of the Hamilton Depression Rating Scale Comparing Screening (Intake Visit) to Visit 6 (Week 15) for the Citalopram Cohort Versus Placebo Cohort	-0.10 units on a scale Standard Error 0.85	1.50 units on a scale Standard Error 0.9

Adverse Events

Citalopram

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Measure	Citalopram n=17 participants at risk 20mg daily citalopram	Placebo n=16 participants at risk Matching daily placebo
Psychiatric disorders worsening depression with suicidal ideation	5.9% 1/17 • Number of events 1 • A systematic assessment of adverse experiences was captured at every encounter beginning at Visit 2 (week 0) and continuing through Visit 7 (week 16) for the randomized treatment vs. placebo period. 17 Participants were randomized to citalopram and 16 participants were randomized to placebo, using a 1:1 allocation.	12.5% 2/16 • Number of events 3 • A systematic assessment of adverse experiences was captured at every encounter beginning at Visit 2 (week 0) and continuing through Visit 7 (week 16) for the randomized treatment vs. placebo period. 17 Participants were randomized to citalopram and 16 participants were randomized to placebo, using a 1:1 allocation.

Other adverse events

Measure	Citalopram n=17 participants at risk 20mg daily citalopram	Placebo n=16 participants at risk Matching daily placebo
Gastrointestinal disorders Constipation	5.9% 1/17 • Number of events 1 • A systematic assessment of adverse experiences was captured at every encounter beginning at Visit 2 (week 0) and continuing through Visit 7 (week 16) for the randomized treatment vs. placebo period. 17 Participants were randomized to citalopram and 16 participants were randomized to placebo, using a 1:1 allocation.	0.00% 0/16 • A systematic assessment of adverse experiences was captured at every encounter beginning at Visit 2 (week 0) and continuing through Visit 7 (week 16) for the randomized treatment vs. placebo period. 17 Participants were randomized to citalopram and 16 participants were randomized to placebo, using a 1:1 allocation.
Gastrointestinal disorders Dry Mouth	5.9% 1/17 • Number of events 1 • A systematic assessment of adverse experiences was captured at every encounter beginning at Visit 2 (week 0) and continuing through Visit 7 (week 16) for the randomized treatment vs. placebo period. 17 Participants were randomized to citalopram and 16 participants were randomized to placebo, using a 1:1 allocation.	0.00% 0/16 • A systematic assessment of adverse experiences was captured at every encounter beginning at Visit 2 (week 0) and continuing through Visit 7 (week 16) for the randomized treatment vs. placebo period. 17 Participants were randomized to citalopram and 16 participants were randomized to placebo, using a 1:1 allocation.
Nervous system disorders Dizziness	11.8% 2/17 • Number of events 2 • A systematic assessment of adverse experiences was captured at every encounter beginning at Visit 2 (week 0) and continuing through Visit 7 (week 16) for the randomized treatment vs. placebo period. 17 Participants were randomized to citalopram and 16 participants were randomized to placebo, using a 1:1 allocation.	0.00% 0/16 • A systematic assessment of adverse experiences was captured at every encounter beginning at Visit 2 (week 0) and continuing through Visit 7 (week 16) for the randomized treatment vs. placebo period. 17 Participants were randomized to citalopram and 16 participants were randomized to placebo, using a 1:1 allocation.
Nervous system disorders Headache	0.00% 0/17 • A systematic assessment of adverse experiences was captured at every encounter beginning at Visit 2 (week 0) and continuing through Visit 7 (week 16) for the randomized treatment vs. placebo period. 17 Participants were randomized to citalopram and 16 participants were randomized to placebo, using a 1:1 allocation.	6.2% 1/16 • Number of events 1 • A systematic assessment of adverse experiences was captured at every encounter beginning at Visit 2 (week 0) and continuing through Visit 7 (week 16) for the randomized treatment vs. placebo period. 17 Participants were randomized to citalopram and 16 participants were randomized to placebo, using a 1:1 allocation.
Reproductive system and breast disorders Ejaculation Disorder	5.9% 1/17 • Number of events 1 • A systematic assessment of adverse experiences was captured at every encounter beginning at Visit 2 (week 0) and continuing through Visit 7 (week 16) for the randomized treatment vs. placebo period. 17 Participants were randomized to citalopram and 16 participants were randomized to placebo, using a 1:1 allocation.	0.00% 0/16 • A systematic assessment of adverse experiences was captured at every encounter beginning at Visit 2 (week 0) and continuing through Visit 7 (week 16) for the randomized treatment vs. placebo period. 17 Participants were randomized to citalopram and 16 participants were randomized to placebo, using a 1:1 allocation.
General disorders Insomnia	5.9% 1/17 • Number of events 1 • A systematic assessment of adverse experiences was captured at every encounter beginning at Visit 2 (week 0) and continuing through Visit 7 (week 16) for the randomized treatment vs. placebo period. 17 Participants were randomized to citalopram and 16 participants were randomized to placebo, using a 1:1 allocation.	12.5% 2/16 • Number of events 2 • A systematic assessment of adverse experiences was captured at every encounter beginning at Visit 2 (week 0) and continuing through Visit 7 (week 16) for the randomized treatment vs. placebo period. 17 Participants were randomized to citalopram and 16 participants were randomized to placebo, using a 1:1 allocation.

Additional Information

Leigh Beglinger, PhD

University of Iowa; Elks Rehab Hospital

Phone: 319-353-4489

Email: leigh-beglinger@elksrehab.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place