The Cognitive Enhancing Effects of D-Cycloserine Among Non-Demented Elderly

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01361633

Enrollment

Registered

2011-05-27

Start date

2008-01-31

Completion date

2009-02-28

Last updated

2021-02-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Placebo, Treatment

Keywords

d-cycloserine, geriatric, neuropsychology, cognition, cognitive-enhancer, aging, neuropsychological functioning

Brief summary

The goal of this study is to determine whether a study medication (d-cycloserine) improves the ability of older adults to perform on tests of neuropsychological functioning. Tests of neuropsychological functioning assess attention, memory, and executive functioning skills (for example, problem-solving, planning and organizing skills). It was hypothesized that participants who received study medication would perform better on neuropsychological tests than would participants who received the sugar pill.

Detailed description

Accumulating data support the augmenting effects of d-cycloserine (DCS) when combined with exposure-based treatment for anxiety disorders. Additional research is needed to determine whether DCS facilitates other forms of cognitive processing (e.g., attention, memory, executive functioning) that are involved in cognitive behavioral therapies which do not rely on extinction as a mechanism of action. This question is particularly important among older adults who have experienced normal age-related declines in cognitive functioning, which may interfere with their ability to benefit from cognitive-behavioral therapies. The aim of the current study was to determine the cognitive enhancing effects of DCS on neuropsychological test performance among healthy older adults. It was hypothesized that participants who received d-cycloserine would demonstrate superior performance on neuropsychological tests than would participants who received placebo.

Interventions

DRUGd-cycloserine

single oral administration of 250 mg d-cycloserine

DRUGSugar Pill

Single oral administration 250 mg Sugar Pill

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

60 Years to No maximum

Healthy volunteers

Yes

Inclusion criteria

* age 60 or older * native English speaker

Exclusion criteria

* diagnosis of current psychiatric disorder * substance abuse past 3 months * cognitive impairment * neurological disorder * poor health or unstable medical condition * positive toxicology screen * current use of isoniazid * current use of trecator * severe renal insufficiency

Design outcomes

Primary

Measure	Time frame	Description
California Verbal Learning Test-II (CLVT-II)	Outcome measures will be collected during a single neuropsychological testing administration lasting approximately 3 hours without patient follow up. Scores for the experimental and control group were compared.	The CLVT-II is an assessment of verbal learning and memory which measures recall and recognition scores, encoding strategies, learning rates and error types. A list learning task with 16 words from 4 semantic categories are read over a series of 5 list presentations. Recall is assessed after learning and at a 20-minute delay. Software produces a report that computes raw and standardized scores. Our dependent variable was the age adjusted t-score for total number of words recalled after 5 trials. A higher score indicated better recall. The maximum possible score was 80 and a minimum was 0.

Secondary

Measure	Time frame	Description
Controlled Oral Word Association Test	Outcome measures will be collected during a single neuropsychological testing administration lasting approximately 3 hours without further patient follow-up	The Controlled Oral Word Association Test is a measure of the ability to orally generate words to a phonemic cue within a 60-second time interval. Age and education-adjusted t-scores were used as the dependent variable. A T-score of 50 is equal to the mean, with a standard deviation of 10 points. A higher T-score is a more favorable outcome.
Wisconsin Card Sort Test	Outcome measures will be collected during a single neuropsychological testing administration lasting approximately 3 hours without further patient follow-up	The Wisconsin Card Sorting Test is a test of rule-learning and conceptual flexibility. The participant is required to learn to sort a series of cards according to one of three principles (color, form or number) based on response feedback. The age-adjusted t-score for total number of errors was used as a dependent variable. A T-score of 50 is equal to the mean, with a standard deviation of 10 points. A higher T-score is a more favorable outcome.
Continuous Performance Test	Outcome measures will be collected during a single neuropsychological testing administration lasting approximately 3 hours without further patient follow-up	Sustained attention was assessed using the Penn version of the Continuous Performance Test. During the CPT the participant responds to a target stimulus (e.g., the letter A), while inhibiting responding to distractor stimuli. Reaction time to correct targets (true positives) was used as the dependent variable. Faster reaction times indicate better performance.
Stroop	Outcome measures will be collected during a single neuropsychological testing administration lasting approximately 3 hours without further patient follow-up	The Stroop Color Word Test is a measure of selective attention and cognitive flexibility. This measure consists of three conditions: word reading, color naming and color-word naming. The interference score (t-score) was used as the dependent variable. A T-score of 50 is equal to the mean, with a standard deviation of 10 points. Higher t-scores represent a more favorable outcome.
Implicit Memory Task	Outcome measures will be collected during a single neuropsychological testing administration lasting approximately 3 hours without further patient follow-up	Participants were presented with 32 stimulus words: 16 neutral and 16 threatening words. After a filler task (crossing out 8's on a sheet of randomized numbers) participants completed a response sheet including the stems for the 32 words presented to participants (primed words) along with stems for the 32 unprimed words. Participants were instructed to write down the first word that came to mind that completes each word stem. The priming effect was determined using the difference score between the correct number of stem completions for primed versus unprimed words. This is a value determined for each participant using the following equation: correct number of stem completions for primed word minus the correct number of stem completions for unprimed words. A larger difference score indicates a stronger implicit memory.
Trails B	Outcome measures will be collected during a single neuropsychological testing administration lasting approximately 3 hours without further patient follow-up	Trails B is a measure of cognitive flexibility. The participant alternates sequencing between numbers and letters. An age and education-adjusted t-score for time to complete the exercise was used as the dependent variable. A T-score of 50 is equal to the mean, with a standard deviation of 10 points. A higher T-score is a more favorable outcome.

Countries

United States

Participant flow

Recruitment details

Inclusion criteria: * age 60+ * fluent in English Exclusion criteria: * current psychiatric disorder other than GAD * substance abuse w/in past 3 months * MMSE score of \<24 * neurological disorder * poor health or unstable medical condition * positive tox screen tests * current use of Isoniazid or Trecator * renal insufficiency

Pre-assignment details

Participants were excluded at Baseline if they had abnormal lab results (6), were taking Aricept (1), were too worried about taking medication (1), or had concurrent depression (1).

Participants by arm

Arm	Count
Medication 250 mg d-cycloserine	25
Sugar Pill Placebo Control	26
Total	51

Baseline characteristics

Characteristic	Sugar Pill	Medication	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	17 Participants	15 Participants	32 Participants
Age, Categorical Between 18 and 65 years	9 Participants	10 Participants	19 Participants
Age, Continuous	70 years STANDARD_DEVIATION 8.44	68 years STANDARD_DEVIATION 6.73	69 years STANDARD_DEVIATION 7.66
Region of Enrollment United States	26 participants	25 participants	51 participants
Sex: Female, Male Female	16 Participants	12 Participants	28 Participants
Sex: Female, Male Male	10 Participants	13 Participants	23 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	3 / 19	4 / 23
serious Total, serious adverse events	0 / 19	0 / 23

Outcome results

Primary

California Verbal Learning Test-II (CLVT-II)

The CLVT-II is an assessment of verbal learning and memory which measures recall and recognition scores, encoding strategies, learning rates and error types. A list learning task with 16 words from 4 semantic categories are read over a series of 5 list presentations. Recall is assessed after learning and at a 20-minute delay. Software produces a report that computes raw and standardized scores. Our dependent variable was the age adjusted t-score for total number of words recalled after 5 trials. A higher score indicated better recall. The maximum possible score was 80 and a minimum was 0.

Time frame: Outcome measures will be collected during a single neuropsychological testing administration lasting approximately 3 hours without patient follow up. Scores for the experimental and control group were compared.

Arm	Measure	Value (MEAN)	Dispersion
Medication	California Verbal Learning Test-II (CLVT-II)	55.84 age adjusted t-scores	Standard Deviation 10.37
Sugar Pill	California Verbal Learning Test-II (CLVT-II)	55.39 age adjusted t-scores	Standard Deviation 10.73

Secondary

Continuous Performance Test

Sustained attention was assessed using the Penn version of the Continuous Performance Test. During the CPT the participant responds to a target stimulus (e.g., the letter A), while inhibiting responding to distractor stimuli. Reaction time to correct targets (true positives) was used as the dependent variable. Faster reaction times indicate better performance.