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

• ClinicalTrials.gov Identifier: NCT01361633
• Recruitment Status: Completed
• First Posted: May 27, 2011
• Results First Posted: June 21, 2012
• Last Update Posted: February 18, 2021
• Sponsor: Hartford Hospital
• Information provided by (Responsible Party): Hartford Hospital

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 (Clinical Trial)
• 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: January 2008
• Actual Primary Completion Date: February 2009
• Actual Study Completion Date: February 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 Name: Seromycin
Placebo Comparator: Sugar Pill	Drug: Sugar Pill; Single oral administration 250 mg Sugar Pill; Other Name: Placebo

Outcome Measures

Primary Outcome Measures :

1. California Verbal Learning Test-II (CLVT-II) [ 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. ]
   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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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

• Ages Eligible for Study: 60 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

United States, Connecticut

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

More Information

• Responsible Party: Hartford Hospital
• ClinicalTrials.gov Identifier: NCT01361633
• Other Study ID Numbers: 126177; DIEF002352HI ( Other Grant/Funding Number: Hartford Hospital )
• First Posted: May 27, 2011
• Results First Posted: June 21, 2012
• Last Update Posted: February 18, 2021
• Last Verified: October 2019

Keywords provided by Hartford Hospital:

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

Additional relevant MeSH terms:

Cycloserine; Anti-Infective Agents, Urinary; Anti-Infective Agents; Renal Agents; Antibiotics, Antitubercular; Antitubercular Agents; Anti-Bacterial Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action