Trial Outcomes & Findings for The Cognitive Enhancing Effects of D-Cycloserine Among Non-Demented Elderly (NCT NCT01361633)

NCT ID: NCT01361633

Last Updated: 2021-02-18

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 51 participants
• Primary outcome timeframe: 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.
• Results posted on: 2021-02-18

Participant Flow

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

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).

Participant milestones

Measure	Medication 250 mg d-cycloserine	Sugar Pill Placebo Control
Overall Study STARTED	25	26
Overall Study COMPLETED	19	23
Overall Study NOT COMPLETED	6	3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Medication n=25 Participants 250 mg d-cycloserine	Sugar Pill n=26 Participants Placebo Control	Total n=51 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	10 Participants n=5 Participants	9 Participants n=7 Participants	19 Participants n=5 Participants
Age, Categorical >=65 years	15 Participants n=5 Participants	17 Participants n=7 Participants	32 Participants n=5 Participants
Age, Continuous	68 years STANDARD_DEVIATION 6.73 • n=5 Participants	70 years STANDARD_DEVIATION 8.44 • n=7 Participants	69 years STANDARD_DEVIATION 7.66 • n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	16 Participants n=7 Participants	28 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	10 Participants n=7 Participants	23 Participants n=5 Participants
Region of Enrollment United States	25 participants n=5 Participants	26 participants n=7 Participants	51 participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Medication n=19 Participants 250mg d-cycloserine	Sugar Pill n=23 Participants Placebo control
California Verbal Learning Test-II (CLVT-II)	55.84 age adjusted t-scores Standard Deviation 10.37	55.39 age adjusted t-scores Standard Deviation 10.73

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Medication n=19 Participants 250mg d-cycloserine	Sugar Pill n=23 Participants Placebo control
Continuous Performance Test	479.50 milliseconds Standard Deviation 42.43	507.80 milliseconds Standard Deviation 77.83

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Medication n=19 Participants 250mg d-cycloserine	Sugar Pill n=23 Participants Placebo control
Controlled Oral Word Association Test	49.58 t-scores Standard Deviation 9.31	46.91 t-scores Standard Deviation 8.14

SECONDARY outcome

Timeframe: Outcome measures will be collected during a single neuropsychological testing administration lasting approximately 3 hours without further patient follow-up

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

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.

Outcome measures

Measure	Medication n=18 Participants 250mg d-cycloserine	Sugar Pill n=23 Participants Placebo control
Wisconsin Card Sort Test	53.50 t scores Standard Deviation 12.37	53.70 t scores Standard Deviation 10.73

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Medication n=19 Participants 250mg d-cycloserine	Sugar Pill n=23 Participants Placebo control
Trails B	52.16 t-scores Standard Deviation 10.99	48.83 t-scores Standard Deviation 9.38

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Medication n=19 Participants 250mg d-cycloserine	Sugar Pill n=23 Participants Placebo control
Stroop	44.68 t-score Standard Deviation 7.17	43.30 t-score Standard Deviation 6.67

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Medication n=19 Participants 250mg d-cycloserine	Sugar Pill n=19 Participants Placebo control
Implicit Memory Task	3.16 correct stem completions Standard Deviation 3.24	2.00 correct stem completions Standard Deviation 3.43

Adverse Events

Medication

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Sugar Pill

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Medication n=19 participants at risk 250 mg d-cycloserine	Sugar Pill n=23 participants at risk Placebo Control
General disorders Drowsiness	10.5% 2/19 • Number of events 2 • 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.	17.4% 4/23 • Number of events 4 • 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.
General disorders Tingling sensation	0.00% 0/19 • 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.	4.3% 1/23 • Number of events 1 • 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.
General disorders Feeling lightheaded	5.3% 1/19 • Number of events 1 • 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.	0.00% 0/23 • 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.

Additional Information

Gretchen Diefenbach, Ph.D.

Anxiety Disorders Center, Institute of Living/Hartford Hospital

Phone: 860-545-7685

Email: gdiefen@harthosp.org

Results disclosure agreements

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