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

• Sponsor: Hartford Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT01361633
• Collaborator: (none)
• Enrollment: 51
• Location: 1
• Arms: 2
• Duration (Months): 13
• Patients Per Site Per Month: 3.9

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Treatment; Placebo	Drug: d-cycloserine; Drug: Sugar Pill	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 51 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: The Cognitive Enhancing Effects of D-Cycloserine Among Non-Demented Elderly
• Study Start Date: Jan 1, 2008
• Actual Primary Completion Date: Feb 1, 2009
• Actual Study Completion Date: Feb 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Medication 250 mg d-cycloserine	Drug: d-cycloserine; single oral administration of 250 mg d-cycloserine; Other Names: Seromycin
Placebo Comparator: Sugar Pill	Drug: Sugar Pill; Single oral administration 250 mg Sugar Pill; Other Names: Placebo

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 60 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Anxiety Disorders Center, Institute of Living/Hartford Hospital	Hartford	Connecticut	United States	06106

Sponsors and Collaborators

• Hartford Hospital

Investigators

• Principal Investigator: Gretchen J. Diefenbach, Ph.D., Hartford Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hartford Hospital
• ClinicalTrials.gov Identifier: NCT01361633
• Other Study ID Numbers: 126177; DIEF002352HI
• First Posted: May 27, 2011
• Last Update Posted: Feb 18, 2021
• Last Verified: Oct 1, 2019

• Keywords provided by Hartford Hospital: d-cycloserine; geriatric; neuropsychology; cognition; cognitive-enhancer; aging; neuropsychological functioning
• Additional relevant MeSH terms: Cycloserine

Study Results

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 Detail	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).

Arm/Group Title	Medication	Sugar Pill
Arm/Group Description	250 mg d-cycloserine	Placebo Control
Period Title: Overall Study
STARTED	25	26
COMPLETED	19	23
NOT COMPLETED	6	3

Baseline Characteristics

Arm/Group Title	Medication	Sugar Pill	Total
Arm/Group Description	250 mg d-cycloserine	Placebo Control	Total of all reporting groups
Overall Participants	25	26	51
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	10 40%	9 34.6%	19 37.3%
>=65 years	15 60%	17 65.4%	32 62.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	68 (6.73)	70 (8.44)	69 (7.66)
Sex: Female, Male (Count of Participants)
Female	12 48%	16 61.5%	28 54.9%
Male	13 52%	10 38.5%	23 45.1%
Region of Enrollment (participants) [Number]
United States	25 100%	26 100%	51 100%

Outcome Measures

1. Primary Outcome

Title	California Verbal Learning Test-II (CLVT-II)
Description	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Medication	Sugar Pill
Arm/Group Description	250mg d-cycloserine	Placebo control
Measure Participants	19	23
Mean (Standard Deviation) [age adjusted t-scores]	55.84 (10.37)	55.39 (10.73)

2. Secondary Outcome

Title	Continuous Performance Test
Description	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.
Time Frame	Outcome measures will be collected during a single neuropsychological testing administration lasting approximately 3 hours without further patient follow-up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Medication	Sugar Pill
Arm/Group Description	250 mg d-cycloserine	Placebo Control
Measure Participants	19	23
Mean (Standard Deviation) [milliseconds]	479.50 (42.43)	507.80 (77.83)

3. Secondary Outcome

Title	Controlled Oral Word Association Test
Description	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.
Time Frame	Outcome measures will be collected during a single neuropsychological testing administration lasting approximately 3 hours without further patient follow-up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Medication	Sugar Pill
Arm/Group Description	250 mg d-cycloserine	Placebo Control
Measure Participants	19	23
Mean (Standard Deviation) [t-scores]	49.58 (9.31)	46.91 (8.14)

4. Secondary Outcome

Title	Wisconsin Card Sort Test
Description	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.
Time Frame	Outcome measures will be collected during a single neuropsychological testing administration lasting approximately 3 hours without further patient follow-up

Outcome Measure Data

Analysis Population Description

sample size for DCS group is n = 18 owing to missing data from one participant.

Arm/Group Title	Medication	Sugar Pill
Arm/Group Description	250mg d-cycloserine	Placebo control
Measure Participants	18	23
Mean (Standard Deviation) [t scores]	53.50 (12.37)	53.70 (10.73)

5. Secondary Outcome

Title	Trails B
Description	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.
Time Frame	Outcome measures will be collected during a single neuropsychological testing administration lasting approximately 3 hours without further patient follow-up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Medication	Sugar Pill
Arm/Group Description	250mg d-cycloserine	Placebo control
Measure Participants	19	23
Mean (Standard Deviation) [t-scores]	52.16 (10.99)	48.83 (9.38)

6. Secondary Outcome

Title	Stroop
Description	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.
Time Frame	Outcome measures will be collected during a single neuropsychological testing administration lasting approximately 3 hours without further patient follow-up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Medication	Sugar Pill
Arm/Group Description	250mg d-cycloserine	Placebo control
Measure Participants	19	23
Mean (Standard Deviation) [t-score]	44.68 (7.17)	43.30 (6.67)

7. Secondary Outcome

Title	Implicit Memory Task
Description	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.
Time Frame	Outcome measures will be collected during a single neuropsychological testing administration lasting approximately 3 hours without further patient follow-up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Medication	Sugar Pill
Arm/Group Description	250mg d-cycloserine	Placebo control
Measure Participants	19	19
Mean (Standard Deviation) [correct stem completions]	3.16 (3.24)	2.00 (3.43)

Adverse Events

Time Frame	Adverse events were monitored via a standardized side effect check list in the one hour time frame after the single dose administration and prior to neuropsychological testing. No spontaneous adverse events outside of this time frame were reported.
Arm/Group Title	Medication		Sugar Pill
Arm/Group Description	250 mg d-cycloserine		Placebo Control
All Cause Mortality
	Medication		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Medication		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/23 (0%)
Other (Not Including Serious) Adverse Events
	Medication		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/19 (15.8%)		4/23 (17.4%)
General disorders
Drowsiness	2/19 (10.5%)	2	4/23 (17.4%)	4
Tingling sensation	0/19 (0%)	0	1/23 (4.3%)	1
Feeling lightheaded	1/19 (5.3%)	1	0/23 (0%)	0

Limitations/Caveats

DCS dosing was 1 hour prior to testing, rather than 4-8; the sample had homogenous cognitive capabilities; repeatedly administering DCS may have enhanced cognitive functioning; the measures may not have adequately tapped hippocampal-based learning.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.