AddictionNCT01531153
Cognitive Enhancement as a Target for Cocaine Pharmacotherapy
A study testing Galantamine in people with Addiction, run by Yale University at 1 site in United States.
Trial summary
Specific Aim #1: To determine if galantamine (8 or 16 mg/day) is more effective than placebo in reducing cocaine use as measured by cocaine urine results and self-report days of use. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Addiction
- What is being tested?
- Galantamine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 93 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2011to Jun 2016
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Male and females, between the ages of 18 and 60
- Are using cocaine more than once per week in the previous 30 days, provide a cocaine-positive urine specimen at screening, and fulfill criteria for current cocaine dependence according to DSM-IV
- For women of child-bearing age, have a negative pregnancy test at screening, agree to adequate contraception to prevent pregnancy, and agree to have monthly pregnancy tests
- Are fluent in English and have a 6th grade or higher reading level; AND
- Can commit to at least 13 weeks of treatment and are willing to be randomized to treatment
Who cannot join
- Meet DSM-IV psychiatric classifications for lifetime schizophrenia or bipolar disorder, or have a depressive or anxiety disorder with current use of a prescribed psychotropic medication that cannot be discontinued
- Current DSM-IV diagnosis of drug or alcohol dependence (other than cocaine, or tobacco)
- Demonstrate significant medical conditions, including asthma or chronic obstructive lung disease, history or current gastrointestinal ulcer, hepatic or renal deficit and cardiac rhythm disturbances or any other medical conditions that the study physician deems contraindicated for galantamine treatment
- Use of other medications including:
- drugs that slow heart rate (e.g., beta-blockers), which may increase the risk of bradycardia and atrioventricular (AV) block and
- non-steroidal anti-inflammatory drugs (NSAIDs); increased potential for developing ulcers/active or occult gastrointestinal bleeding
- Have a screening liver function test (AST or ALT) greater than 3 times normal; OR
- Known allergy or adverse reaction to galantamine
Trial locations and contacts
1 site in 1 country.
United States1 site
Department of Veterans Affairs
West Haven, Connecticut, 06516
About this study
Specific Aim #1: To determine if galantamine (8 or 16 mg/day) is more effective than placebo in reducing cocaine use as measured by cocaine urine results and self-report days of use.
Specific Aim # 2: To determine if galantamine (8 or 16 mg/day) is more effective than placebo in improving attention, assessed with the Rapid Visual Information Processing (RVIP) and the Simple Reaction Time (SRT) tests Specific Aim # 3: To determine if improvement in attention during the first four weeks of treatment will mediate galantamine's efficacy in reducing cocaine use.
Read the detailed description
This will be a double-blind, placebo-controlled, randomized clinical trial. One hundred and twenty cocaine-dependent men and women will be randomized to one of three treatment groups: placebo (n=40), 8 mg/day (n=40), and 16 mg/day (n=40) of extended release (ER) galantamine. An urn randomization will be used to balance the groups for gender, severity of cocaine use (measured by days of cocaine use), baseline cognitive functioning [determined via the Shipley Institute of Living Scale (SILS)], and smoking status. Gender and severity of cocaine use have been shown to predict treatment responses in cocaine users (76). Similarly, balancing the treatment groups for baseline cognitive functioning, assessed with the SILS scores, will minimize the influence of baseline differences on cognitive outcomes (77, 78). Smoking status is also an important baseline variable, given galantamine's actions on nicotinic receptors and its potential efficacy for smoking cessation (65). The initial dose of galantamine will be 8 mg/day as a single dose, as recommended for clinical use. For those assigned to 16 mg/day, the dose of galantamine will be increased to 16 mg at the end of week 4. Treatment groups will remain on their full dosage through week 13. All participants will receive contingency management (CM) targeting treatment compliance. In three previous cocaine pharmacotherapy trials using bupropion, desipramine or levodopa, medication efficacy on cocaine use was evident only when medications were combined with CM, but not with standard care (79-81). These findings provide a strong rationale for using CM in our clinical trial.
Recruitment is continuing. This protocol was amended as of May 2014 to come to one dispensing visit and up too, two clinic visits. The payment has changed from gift cards to cash. This change should help increase the number of completers.
Currently there are 40 completers with 9 active and 6 in follow up phase. The follow up phase ended June 2016. Currently in analysis.
- Conditions
- Addiction
- Being tested
- Galantamine, Placebo
- Keywords
- Cocaine use decreases, increases or stays the same
- Medical subject headings
- Behavior, Addictive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GalantamineDrug
Also called Razadyne, Razadyne ER
8mg or 16mg
PlaceboDrug
Also called Sugar Pill
Placebo dose.
| Study group | Role | What they receive |
|---|---|---|
| Sugar Pill | Active comparator | Sugar Pill will be compared with the active medication Galantamine Receives: Drug: Placebo |
| Galantamine | Active comparator | Comparing the active medication with the placebo medication to see if the self administration cocaine decreases. Receives: Drug: Galantamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Urine Toxicology
Presented are the average number of urine samples positive for cocaine over 12 weeks. This outcome was corrected from the protocol registration when the study data were entered.
Measured: 12 weeks
Secondary outcomes (16)
Heart Rate
Pulse
Measured: once a day for up to two days over 12 Weeks
Blood Pressure- Systolic
Blood Pressure is taken for safety reasons
Measured: 2 times a week for 12 weeks
Blood Pressure- Diastolic
Blood Pressure is taken for safety reasons
Measured: 2 times a week for 12 weeks
CANTAB RVIP Measure: RVP A
RVIP is a computerized measure of attention. This is given at baseline and every 4 weeks over the course of the 12-week study. RVP A' (aka RVIP A PRIME): is a signal detection measure of target sensitivity (i.e., successful response to targets and withholding of responses to non-targets). Range of 0 to 1. Higher scores are better.
Measured: Baseline and 12 Weeks
CANTAB RVIP Measure: RVP B
RVIP is a computerized measure of attention. This is given at baseline and every 4 weeks over the course of the 12-week study. RVP B": A measure of response bias (i.e., bias towards under-responding (to targets) versus over-responding (i.e., to non-targets)) range from -1 to +1, respectively.
Measured: Baseline and 12 Weeks
CANTAB RVIP Measure: RVP FALSE ALARM
RVIP is a computerized measure of attention. This is given at baseline and every 4 weeks over the course of the 12-week study. RVP FALSE ALARM is probability of false alarm. False alarms are responses to non-targets. Higher numbers are worse (i.e., could be seen as a measure of poor response inhibition). Scores range from 0-1 where 1 is the least desirable probablity.
Measured: Baseline and 12 Weeks
CANTAB SST- SSRT
This is the CANTAB SST measure which evaluates response inhibition. Stop Signal Reaction Time (SSRT): The estimate of the length of time between the go stimulus and the stop stimulus at which the subject is able to successfully inhibit their response on 50% of the trials. Range of scores from 0 to 1500 (unit=milliseconds) and lower scores are 'better'.
Measured: Baseline and 12 Weeks
CANTAB SST- Median Correct
This is the CANTAB SST measure which evaluates response inhibition. Stop Signal Reaction Time (SSRT): The estimate of the length of time between the go stimulus and the stop stimulus at which the subject is able to successfully inhibit their response on 50% of the trials. Range of scores from 0 to 1500 (unit=milliseconds) and lower scores are 'better'. Median correct is the median of response times across 'go' trials where the subject has responded on the correct button (right or left).
Measured: Baseline and 12 Weeks
CANTAB SST- SD Correct
This is the CANTAB SST measure which evaluates response inhibition. Stop Signal Reaction Time (SSRT): The estimate of the length of time between the go stimulus and the stop stimulus at which the subject is able to successfully inhibit their response on 50% of the trials. Range of scores from 0 to 1500 (unit=milliseconds) and lower scores are 'better'. SD Correct is the standard deviation of response times across 'go' trials where the subject has responded on the correct button (right or left).
Measured: Baseline and 12 Weeks
Stroop- RT Correct Neutral
Drug Stroop Task is a computerized task which presents words either cocaine-related ('drug') words or non-drug-related ('neutral') words written in colored font. The subject is asked to press a button to indicate the color of the font as quickly and accurately as possible. The task is thought to measure attentional bias to drug-related stimuli. RT Correct Neutral is the mean response time to neutral trials where the subject pressed the correct color response.
Measured: weeks 0, 4, 8, 12, 16, 24, 36
Stroop- RT Correct Drug
Drug Stroop Task is a computerized task which presents words either cocaine-related ('drug') words or non-drug-related ('neutral') words written in colored font. The subject is asked to press a button to indicate the color of the font as quickly and accurately as possible. The task is thought to measure attentional bias to drug-related stimuli. RT Correct Drug is the mean response time to drug trials where the subject pressed the correct color response.
Measured: weeks 0, 4, 8, 12, 16, 24, 36
Stroop- Effect Drug Neutral Mean Correct
Drug Stroop Task is a computerized task which presents words either cocaine-related ('drug') words or non-drug-related ('neutral') words written in colored font. The subject is asked to press a button to indicate the color of the font as quickly and accurately as possible. The task is thought to measure attentional bias to drug-related stimuli. Stroop Effect is difference in response time to drug versus neutral trials (i.e., RT Correct Drug - RT Correct Neutral). A larger stroop effect is 'worse' (thought to indicate more attentional bias to drug related stimuli).
Measured: weeks 0, 4, 8, 12, 16, 24, 36
Digit Span- LDSF
Digit Span Task description: Orally administered (not computerized) task where subjects are read-aloud lists of digits and asked to repeat them in the same order they heard them (Forward condition). Subjects are given a pair of lists for each digit length - and given a point for each list they get entirely correct. If they get at least one out of the two correct for that length, then the researcher gives them another one of a longer length (one digit longer). If they get both wrong at a given length- that task is ended. The task is then repeated with different digit lists to recall, but they are asked to repeat them or in the reverse order that they heard them (Backward condition). Longest Digit Span Forward (LDSF) is the longest digit span a participant gets correct, in the forward condition. Higher scores are better (Scale of 0 to 9).
Measured: Baseline and 12 Weeks
Digit Span- DSF
Digit Span Task description: Orally administered (not computerized) task where subjects are read-aloud lists of digits and asked to repeat them in the same order they heard them (Forward condition). Subjects are given a pair of lists for each digit length - and given a point for each list they get entirely correct. If they get at least one out of the two correct for that length, then the researcher gives them another one of a longer length (one digit longer). If they get both wrong at a given length- that task is ended. The task is then repeated with different digit lists to recall, but they are asked to repeat them or in the reverse order that they heard them (Backward condition). Digit Span Forward (DSF) is the number of digit span trials participants got correct in the forward condition. Higher scores are better (Scale of 0 to 14).
Measured: Baseline and 12 Weeks
Digit Span- LDSB
Digit Span Task description: Orally administered (not computerized) task where subjects are read-aloud lists of digits and asked to repeat them in the same order they heard them (Forward condition). Subjects are given a pair of lists for each digit length - and given a point for each list they get entirely correct. If they get at least one out of the two correct for that length, then the researcher gives them another one of a longer length (one digit longer). If they get both wrong at a given length- that task is ended. The task is then repeated with different digit lists to recall, but they are asked to repeat them or in the reverse order that they heard them (Backward condition). Longest Digit Span Backward (LDSB) is the longest digit span participants got correct, in the backward condition. Higher scores are better (Scale of 0 to 8).
Measured: Baseline and 12 Weeks
Digit Span- DSB
Digit Span Task description: Orally administered (not computerized) task where subjects are read-aloud lists of digits and asked to repeat them in the same order they heard them (Forward condition). Subjects are given a pair of lists for each digit length - and given a point for each list they get entirely correct. If they get at least one out of the two correct for that length, then the researcher gives them another one of a longer length (one digit longer). If they get both wrong at a given length- that task is ended. The task is then repeated with different digit lists to recall, but they are asked to repeat them or in the reverse order that they heard them (Backward condition). Digit Span Forward (DSB) is the number of digit span trials participants got correct in the backward condition. Higher scores are better (Scale of 0 to 14).
Measured: Baseline and 12 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2012 (estimated)
- Study startSep 2011
- Primary completionJun 2016
- Study completionJun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for AddictionStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 93 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Sponsor
- Investigators
- Mehmet Sofuoglu, M.D., Ph.D., Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01531153
- Sponsor's protocol ID
- 1007007119
- Other IDs
- R01DA029577
- Status last verified
- Oct 2018
- First submitted
- 7 Dec 2011
- Last updated
- 26 Oct 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cognitive Enhancement as a Target for Cocaine Pharmacotherapy
- ClinicalTrials.gov ID
- NCT01531153
- Acronym / sponsor ID
- 1007007119
- Conditions
- Addiction
- Keywords
- Cocaine use decreases, increases or stays the same
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 93 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- Sep 2011
- Primary completion
- Jun 2016 (actual)
- Study completion
- Jun 2016 (actual)
- First posted
- 10 Feb 2012 (estimated)
- Results
- Posted 26 Oct 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Specific Aim #1: To determine if galantamine (8 or 16 mg/day) is more effective than placebo in reducing cocaine use as measured by cocaine urine results and self-report days of use.
Specific Aim # 2: To determine if galantamine (8 or 16 mg/day) is more effective than placebo in improving attention, assessed with the Rapid Visual Information Processing (RVIP) and the Simple Reaction Time (SRT) tests Specific Aim # 3: To determine if improvement in attention during the first four weeks of treatment will mediate galantamine's efficacy in reducing cocaine use.
Detailed description
This will be a double-blind, placebo-controlled, randomized clinical trial. One hundred and twenty cocaine-dependent men and women will be randomized to one of three treatment groups: placebo (n=40), 8 mg/day (n=40), and 16 mg/day (n=40) of extended release (ER) galantamine. An urn randomization will be used to balance the groups for gender, severity of cocaine use (measured by days of cocaine use), baseline cognitive functioning [determined via the Shipley Institute of Living Scale (SILS)], and smoking status. Gender and severity of cocaine use have been shown to predict treatment responses in cocaine users (76). Similarly, balancing the treatment groups for baseline cognitive functioning, assessed with the SILS scores, will minimize the influence of baseline differences on cognitive outcomes (77, 78). Smoking status is also an important baseline variable, given galantamine's actions on nicotinic receptors and its potential efficacy for smoking cessation (65). The initial dose of galantamine will be 8 mg/day as a single dose, as recommended for clinical use. For those assigned to 16 mg/day, the dose of galantamine will be increased to 16 mg at the end of week 4. Treatment groups will remain on their full dosage through week 13. All participants will receive contingency management (CM) targeting treatment compliance. In three previous cocaine pharmacotherapy trials using bupropion, desipramine or levodopa, medication efficacy on cocaine use was evident only when medications were combined with CM, but not with standard care (79-81). These findings provide a strong rationale for using CM in our clinical trial.
Recruitment is continuing. This protocol was amended as of May 2014 to come to one dispensing visit and up too, two clinic visits. The payment has changed from gift cards to cash. This change should help increase the number of completers.
Currently there are 40 completers with 9 active and 6 in follow up phase. The follow up phase ended June 2016. Currently in analysis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sugar Pill | Active comparator | Drug: PlaceboSugar Pill will be compared with the active medication Galantamine |
| Galantamine | Active comparator | Drug: GalantamineComparing the active medication with the placebo medication to see if the self administration cocaine decreases. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Male and females, between the ages of 18 and 60
- Are using cocaine more than once per week in the previous 30 days, provide a cocaine-positive urine specimen at screening, and fulfill criteria for current cocaine dependence according to DSM-IV
- For women of child-bearing age, have a negative pregnancy test at screening, agree to adequate contraception to prevent pregnancy, and agree to have monthly pregnancy tests
- Are fluent in English and have a 6th grade or higher reading level; AND
- Can commit to at least 13 weeks of treatment and are willing to be randomized to treatment
Key exclusion criteria (8 listed)
- Meet DSM-IV psychiatric classifications for lifetime schizophrenia or bipolar disorder, or have a depressive or anxiety disorder with current use of a prescribed psychotropic medication that cannot be discontinued
- Current DSM-IV diagnosis of drug or alcohol dependence (other than cocaine, or tobacco)
- Demonstrate significant medical conditions, including asthma or chronic obstructive lung disease, history or current gastrointestinal ulcer, hepatic or renal deficit and cardiac rhythm disturbances or any other medical conditions that the study physician deems contraindicated for galantamine treatment
- Use of other medications including:
- Have a screening liver function test (AST or ALT) greater than 3 times normal; OR
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GalantamineAlso: Razadyne, Razadyne ER8mg or 16mg | Drug | Galantamine |
| PlaceboAlso: Sugar PillPlacebo dose. | Drug | Sugar Pill |
Primary outcome
Urine Toxicology
Time frame: 12 weeks
Presented are the average number of urine samples positive for cocaine over 12 weeks. This outcome was corrected from the protocol registration when the study data were entered.
16 secondary outcomes
Heart Rate
Time frame: once a day for up to two days over 12 Weeks
Blood Pressure- Systolic
Time frame: 2 times a week for 12 weeks
Blood Pressure- Diastolic
Time frame: 2 times a week for 12 weeks
CANTAB RVIP Measure: RVP A
Time frame: Baseline and 12 Weeks
CANTAB RVIP Measure: RVP B
Time frame: Baseline and 12 Weeks
CANTAB RVIP Measure: RVP FALSE ALARM
Time frame: Baseline and 12 Weeks
CANTAB SST- SSRT
Time frame: Baseline and 12 Weeks
CANTAB SST- Median Correct
Time frame: Baseline and 12 Weeks
CANTAB SST- SD Correct
Time frame: Baseline and 12 Weeks
Stroop- RT Correct Neutral
Time frame: weeks 0, 4, 8, 12, 16, 24, 36
Stroop- RT Correct Drug
Time frame: weeks 0, 4, 8, 12, 16, 24, 36
Stroop- Effect Drug Neutral Mean Correct
Time frame: weeks 0, 4, 8, 12, 16, 24, 36
Digit Span- LDSF
Time frame: Baseline and 12 Weeks
Digit Span- DSF
Time frame: Baseline and 12 Weeks
Digit Span- LDSB
Time frame: Baseline and 12 Weeks
Digit Span- DSB
Time frame: Baseline and 12 Weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mehmet Sofuoglu, M.D., Ph.D. principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Galantamine in people with Addiction, run by Yale University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Oct 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Urine Toxicology (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2018.