Galantamine Effects on Cognitive Function in Abstinent Cocaine Users

• ClinicalTrials.gov Identifier: NCT00606801
• Recruitment Status: Completed
• First Posted: February 5, 2008
• Results First Posted: July 31, 2013
• Last Update Posted: March 15, 2021
• Sponsor: Yale University
• Collaborator: National Institute on Drug Abuse (NIDA)
• Information provided by (Responsible Party): Yale University

Study Description

Brief Summary:

To evaluate galantamine's effects on cognitive performance in abstinent cocaine users. Galantamine, a medication approved for treatment of Alzheimer's disease, is an acetylcholine esterase inhibitor. Galantamine also directly potentiates nicotine receptors. Both of these effects may result in improved cognitive performance in a group of subjects known to have impaired performance in various cognitive tasks.

Condition or disease	Intervention/treatment	Phase
Cocaine Abuse	Drug: Galantamine; Drug: placebo	Not Applicable

Detailed Description:

Galantamine, compared to placebo, will improve cognitive performance in abstinent cocaine users. The cognitive performance will be measured with the Stroop test and 3 Cambridge Neuropsychological Test Automated Battery (CANTAB) tests: Paired Associate Learning (PAL), Delayed Pattern Recognition Memory (PRM),and Rapid Visual Information Processing (RVIP). Performance on these tests has been shown to be impaired in abstinent cocaine users, compared to healthy controls.

Galantamine, compared to placebo, will not be associated with any significant changes in mood. Monitoring of mood will be achieved with 3 mood scales: 1) Center for Epidemiologic Studies Depression (CES-D) scale, Positive and Negative Affect Schedule (PANAS) and the Profile of Mood States (POMS).

Currently this study is completed, Patients are no longer being enrolled. There were 28 completers. This study has been published.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 34 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Galantamine Effects on Cognitive Function in Abstinent Cocaine Users
• Study Start Date: June 2007
• Actual Primary Completion Date: February 2009
• Actual Study Completion Date: February 2009

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Galantamine 8 mg/day; Galantamine 8 mg/day	Drug: Galantamine; Galantamine 8 mg/day; Other Names: Nivalin,; Razadyne,; Razadyne ER,; Reminyl,; Lycoremine
Placebo Comparator: Placebo; placebo	Drug: placebo; sugar pill; Other Name: Sugar Pill

Outcome Measures

Primary Outcome Measures :

1. Performance on the Cambridge Neuropsychological Test Automated Battery (CANTAB) - RVIP Reaction Time [ Time Frame: Baseline, Day 5 and Day 10 ]
   Rapid Visual Processing test (RVIP) is a measure of sustained attention with a small working memory component that is sensitive to cholinergic enhancers. In the RVIP, subjects must detect either odd or even 3 digit sequences appearing in a box in a pseudo-random order at 100 digits per minute. Reaction time (RT) to correct answers was measured.
2. Performance on the Cambridge Neuropsychological Test Automated Battery (CANTAB) - RVIP Total Hits [ Time Frame: Baseline, Day 5 and Day 10 ]
   Rapid Visual Processing test (RVIP) is a measure of sustained attention with a small working memory component that is sensitive to cholinergic enhancers. In the RVIP, subjects must detect either odd or even 3 digit sequences appearing in a box in a pseudo-random order at 100 digits per minute. The total hits were measured
3. Performance on the Cambridge Neuropsychological Test Automated Battery (CANTAB) - RVIP Total Correct Rejections [ Time Frame: Baseline, Day 5 and Day 10 ]
   Rapid Visual Processing test (RVIP) is a measure of sustained attention with a small working memory component that is sensitive to cholinergic enhancers. In the RVIP, subjects must detect either odd or even 3 digit sequences appearing in a box in a pseudo-random order at 100 digits per minute. The number of correct rejections was measured.
4. Performance on the Cambridge Neuropsychological Test Automated Battery (CANTAB) - RVIP A' (Sensitivity to Target Sequences) [ Time Frame: Baseline, Day 5 and Day 10 ]
   Rapid Visual Processing test (RVIP) is a measure of sustained attention with a small working memory component that is sensitive to cholinergic enhancers. In the RVIP, subjects must detect either odd or even 3 digit sequences appearing in a box in a pseudo-random order at 100 digits per minute. A' is a measure of sensitivity to target sequences and it reflects probabilities of hits and false alarms to provide a score of sensitivity to the target regardless of response tendency. The scores range from 0 (bad) to 1 (good).
5. Performance on the Cambridge Neuropsychological Test Automated Battery (CANTAB) - RVIP B' (Strength to Detect to Target Sequences) [ Time Frame: Baseline, Day 5 and Day 10 ]
   Rapid Visual Processing test (RVIP) is a measure of sustained attention with a small working memory component that is sensitive to cholinergic enhancers. In the RVIP, subjects must detect either odd or even 3 digit sequences appearing in a box in a pseudo-random order at 100 digits per minute. B reflects the probability of hits and false alarms to provide a measure of the participants tendency to respond regardless of whether the target sequence is presented. The scores range from -1 to +1 with scores near +1 indicative of a subject that gave few false alarms.
6. Paired Associate Learning (PAL) - Stages Complete [ Time Frame: Baseline, Day 5 and Day 10 ]
   Rapid Visual Processing test (RVIP) is a measure of sustained attention with a small working memory component that is sensitive to cholinergic enhancers. In the Paired Associate Learning (PAL) task, boxes are displayed on the screen and are opened in a random order. One or more of the boxes will contain a pattern. After the subjects have seen the patterns behind each box, the patterns are then displayed in the middle of the screen, one at a time, and the subject must touch the box where the pattern was originally located. An error will cause the test to open the boxes again to remind the subject of their locations. The number of boxes with patterns increases throughout the test. The stages completed and number of errors are measures of interest.
7. Paired Associate Learning (PAL) - Mean Errors [ Time Frame: Baseline, Day 5 and Day 10 ]
   Rapid Visual Processing test (RVIP) is a measure of sustained attention with a small working memory component that is sensitive to cholinergic enhancers. In the Paired Associate Learning (PAL) task, boxes are displayed on the screen and are opened in a random order. One or more of the boxes will contain a pattern. After the subjects have seen the patterns behind each box, the patterns are then displayed in the middle of the screen, one at a time, and the subject must touch the box where the pattern was originally located. An error will cause the test to open the boxes again to remind the subject of their locations. The number of boxes with patterns increases throughout the test. The stages completed and number of errors are measures of interest.
8. Pattern Recognition Memory (PRM) - Response Time for Correct Answers [ Time Frame: Baseline, Day 5 and Day 10 ]
   In the PRM, the subject is presented with a series of 12 visual patterns, one at a time, in the center of the screen. These patterns are designed so that they cannot easily be given verbal labels. In the recognition phase, the subject is required to choose between a pattern they have already seen and a novel pattern. The time to correct answer was measured.
9. Pattern Recognition Memory (PRM) - Number Correct Answers [ Time Frame: Baseline, Day 5 and Day 10 ]
   Pattern Recognition Memory (PRM) tests visual pattern recognition memory in a two choice forced discrimination paradigm. 12 visual patterns are presented, then the subject must choose between each of these patterns and a novel pattern. The number of correct responses are measured.

Secondary Outcome Measures :

1. Performance on the Sustained Attention to Response Task (SART) - Number of Errors on NoGo Trials [ Time Frame: Baseline, Day 5 and Day 10 ]

   The SART is a Go / NoGo task measuring the ability to activate or inhibit responses. In this 4.5 minute task, 225 single digits (25 × 9 digits) were presented on a computer monitor. Each digit was presented for 250 ms, and was immediately followed by a mask for 900 ms. The mask consists of a ring with a diagonal cross in the center. Subjects were instructed to press a spacebar to every digit except the 3, and to give equal importance to speed and accuracy. Responses were allowed during the presentation of both the digit and mask. The digits were presented in a different random order for each subject. There were 18 practice trials, containing 2 no-response targets (3s). For the Go/NoGo task, response inhibition was measured as the number of errors on the no- Go trials, with low errors indicating better response inhibition.

   Complete data for 3 subjects in the Placebo group, and for 1 subject in the galantamine group were not capture do to experimenter and computer errors.

2. Performance on the Sustained Attention to Response Task (SART)- Number of Errors on Go Trials [ Time Frame: Baseline, Day 5 and Day 10 ]

   The SART is a Go / NoGo task measuring the ability to activate or inhibit responses. In this 4.5 minute task, 225 single digits (25 × 9 digits) were presented on a computer monitor. Each digit was presented for 250 ms, and was immediately followed by a mask for 900 ms. The mask consists of a ring with a diagonal cross in the center. Subjects were instructed to press a spacebar to every digit except the 3, and to give equal importance to speed and accuracy. Responses were allowed during the presentation of both the digit and mask. The digits were presented in a different random order for each subject. There were 18 practice trials, containing 2 no-response targets (3s). The number of errors on Go trials reflected the response activation function, with fewer errors indicating greater response activation.

   Complete data for 3 subjects in the Placebo group, and for 1 subject in the galantamine group were not capture do to experimenter and computer errors.

3. Performance on the Sustained Attention to Response Task (SART)- Mean Reaction Time for Correct Press on Go Trial [ Time Frame: Baseline, Day 5 and Day 10 ]

   The SART is a Go / NoGo task measuring the ability to activate or inhibit responses. In this 4.5 minute task, 225 single digits (25 × 9 digits) were presented on a computer monitor. Each digit was presented for 250 ms, and was immediately followed by a mask for 900 ms. The mask consists of a ring with a diagonal cross in the center. Subjects were instructed to press a spacebar to every digit except the 3, and to give equal importance to speed and accuracy. Responses were allowed during the presentation of both the digit and mask. The digits were presented in a different random order for each subject. There were 18 practice trials, containing 2 no-response targets (3s).

   For the Go trial, the reaction time reflected the response activation function, faster reaction time indicating greater response activation.

   Complete data for 3 subjects in the Placebo group, and for 1 subject in the galantamine group were not capture do to experimenter and computer errors.

4. Performance on the Modified Stroop Task (Cocaine-Stroop)- Reaction Time [ Time Frame: Baseline, Day 5 and Day 10 ]
   The Cocaine-Stroop task measures attention capture (attentional bias) secondary to cocaine cues; (Stroop effect - calculated as the difference between mean RT on cocaine words and mean RT on control words). Subjects completed 2 counterbalanced blocks (150 trials per block). One block contained 15 cocaine words and neutral words in a mixed order. The other block contained 15 control words matched in length and frequency to cocaine words, and a different set of neutral words. Subjects were required to indicate the colors in which the words were written as quickly and accurately as possible. Reaction times for identification of word color was measured. In addition, the difference in RT to words following cocaine and control words were measured (carry-over effect). Complete data for 3 participants (2 placebo and 1 galantamine) were not capture due to experimenter and computer errors.
5. Performance on the Modified Stroop Task (Cocaine-Stroop)- Stroop Effect [ Time Frame: Baseline, Day 5 and Day 10 ]
   The Cocaine-Stroop task measures attention capture (attentional bias) secondary to cocaine cues; (Stroop effect - calculated as the difference between mean RT on cocaine words and mean RT on control words). Subjects completed 2 counterbalanced blocks (150 trials per block). One block contained 15 cocaine words and neutral words in a mixed order. The other block contained 15 control words matched in length and frequency to cocaine words, and a different set of neutral words. Subjects were required to indicate the colors in which the words were written as quickly and accurately as possible. Reaction times for identification of word color was measured. In addition, the difference in RT to words following cocaine and control words were measured (carry-over effect). Complete data for 3 participants (2 placebo and 1 galantamine) were not capture due to experimenter and computer errors.
6. Performance on the Modified Stroop Task (Cocaine-Stroop)- Carry-over Effect [ Time Frame: Baseline, Day 5 and Day 10 ]
   The Cocaine-Stroop task measures attention capture (attentional bias) secondary to cocaine cues; (Stroop effect - calculated as the difference between mean RT on cocaine words and mean RT on control words). Subjects completed 2 counterbalanced blocks (150 trials per block). One block contained 15 cocaine words and neutral words in a mixed order. The other block contained 15 control words matched in length and frequency to cocaine words, and a different set of neutral words. Subjects were required to indicate the colors in which the words were written as quickly and accurately as possible. Reaction times for identification of word color was measured. In addition, the difference in RT to words following cocaine and control words were measured (carry-over effect). Complete data for 3 participants (2 placebo and 1 galantamine) were not capture due to experimenter and computer errors.

Eligibility Criteria

• Ages Eligible for Study: 21 Years to 50 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Male and females, between the ages 21 and 50
• Fulfill criteria for past cocaine dependence
• No cocaine use for the past 30 days
• No other current dependence or abuse of other drugs or alcohol
• No current medical problems and normal ECG
• Not pregnant,nor breast feeding,
• Using acceptable birth control methods.

Exclusion Criteria:

• Current major psychiatric illness including mood, psychotic or anxiety disorders
• History of major medical illnesses; including asthma or chronic obstructive lung disease, history or current gastrointestinal ulcer, hepatic or renal impairment and cardiac rhythm disturbances
• Use of other medications including,drugs that slow heart rate
• Known allergy to galantamine

Contacts and Locations

Locations

United States, Connecticut

Veterans Affairs Hospital

West Haven, Connecticut, United States, 06516

Sponsors and Collaborators

Yale University

National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Mehmet Sofuoglu, M.D., Ph.D.; Yale University Associate Professor

More Information

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT00606801
• Other Study ID Numbers: 0706002768; P50DA009241 ( U.S. NIH Grant/Contract ); B Rounsaville ( Other Identifier: Principal Investigator of P50 grant )
• First Posted: February 5, 2008
• Results First Posted: July 31, 2013
• Last Update Posted: March 15, 2021
• Last Verified: February 2021

Keywords provided by Yale University:

cognitive enhancers; Nootropic Agents

Additional relevant MeSH terms:

Cocaine-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Galantamine; Cholinesterase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Neurotransmitter Agents; Physiological Effects of Drugs; Parasympathomimetics; Autonomic Agents; Peripheral Nervous System Agents; Nootropic Agents