Cocaine DependencePhase 2NCT01406522
Tacrine Effects on Cocaine Self-Administration and Pharmacokinetics
A Phase 2 study testing Oral tacrine in people with Cocaine Dependence, run by Midwest Biomedical Research at 1 site in United States.
Trial summary
No medications are currently available for treatment of psychostimulant addiction, a compulsive preoccupation with use of cocaine and related compounds. Tacrine, a medication that is currently prescribed for Alzheimer's disease, can decrease the amount of cocaine injections that laboratory animals choose to inject by… Read more about this study
- Who is it for?
- Ages 21 to 50 years
- Conditions the study is for
- Cocaine Dependence
- What is being tested?
- Oral tacrine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2012to Nov 2013
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 21 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Meets DSM-IV-TR criteria for cocaine abuse or dependence, with at least one cocaine-positive urine specimen within the six weeks prior to enrollment.
- Has used cocaine for a duration of at least 6 months, with at least weekly use during the last 30 days by a rapid route of administration (either smoked or intravenous injection).
- Is male or female, between 21 and 50 years old.
Who cannot join
- Has a history of a medical adverse reaction to cocaine or other psychostimulants, including loss of consciousness, chest pain, cardiac ischemia, or seizure.
- Has any current Axis I psychiatric disorder other than drug abuse or dependence.
- Meets DSM-IV-TR criteria for dependence on opiates, benzodiazepines, alcohol, or other sedative-hypnotics.
Trial locations and contacts
1 site in 1 country.
United States1 site
Kansas City VA Medical Center
Kansas City, Missouri, 64128
About this study
No medications are currently available for treatment of psychostimulant addiction, a compulsive preoccupation with use of cocaine and related compounds. Tacrine, a medication that is currently prescribed for Alzheimer's disease, can decrease the amount of cocaine injections that laboratory animals choose to inject by vein. This project will determine if tacrine can also decrease cocaine-motivated behavior for human subjects in a laboratory setting.
Read the detailed description
Background Reinforcing effects of cocaine are believed to arise through release of dopamine (DA) at the nucleus accumbens by neurons in the ventral tegmental area. Activation of cholinergic receptors on the cell bodies of these neurons can enhance DA release. Elevated levels of acetylcholine (ACh) in the nucleus accumbens may also serve to inhibit appetitive behaviors. Cholinesterase inhibitors such as tacrine increase synaptic levels of ACh by preventing its inactivation by acetylcholinesterase (AChE) or butyrylcholinesterase (BuChE), and can improve learning and memory. In animals, cholinesterase inhibitors can attenuate cocaine self-administration and conditioned place preference. Tacrine is a centrally acting, reversible inhibitor of AChE and BuChE that is approved for treatment of Alzheimer's disease. In addition to its effects on the cholinergic system, tacrine can potentiate the actions of monoamines, including DA. Although use of tacrine has declined because of requirements for monitoring of potential liver toxicity and pharmacokinetics that necessitate multiple daily doses, it is more potent than other cholinesterase inhibitors in attenuating cocaine self-administration in animals. Pretreatment with tacrine can produce long-lasting reductions in cocaine-reinforced behavior in rats, described as persistent attenuation (cocaine self-administration is decreased by more than 80% over a period of three days during which no additional cholinesterase inhibitor is administered, see Figure 1). No previous studies have evaluated whether tacrine can modify the effects of cocaine in humans.
Rationale To our knowledge, tacrine is the only compound that can produce persistent attenuation in rats treated with clinically relevant doses. If similar effects were observed in humans, this would lead to an important paradigm shift for substance abuse treatment, in that large reductions in cocaine-reinforced behavior could be produced without the need for continuous dosing with a medication. This scenario could remove the requirement for continued compliance with oral dosing in some patients with its associated potential for toxicity.
Specific Aims:
- Evaluate whether tacrine treatment causes persistent attenuation of cocaine-reinforced behavior in humans.
- Determine the effectiveness of pretreatment with tacrine in attenuating cocaine-induced craving.
- Evaluate plasma levels of cocaine and characterize the bioavailability of tacrine in individual patients.
Methods This is a randomized, double-blind, double-dummy, placebo-controlled, inpatient, single-center, parallel-group evaluation of the potential for oral tacrine to modify cocaine self-administration, cocaine-induced craving, and the pharmacokinetics of cocaine and tacrine. To evaluate the occurrence of persistent attenuation, the subjective and reinforcing effects of intravenous cocaine will be determined during oral treatment and three days following its discontinuation.
- Conditions
- Cocaine Dependence
- Being tested
- Oral tacrine, Oral placebo
- Keywords
- Acetylcholine, Cholinesterases, Cocaine, Self-Administration
- Medical subject headings
- Cocaine-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral tacrineDrug
Tacrine, 160 mg per day, four times daily
Oral placeboDrug
Microcrystalline cellulose
| Study group | Role | What they receive |
|---|---|---|
| Oral placebo | Placebo comparator | Inactive treatment Receives: Drug: Oral placebo |
| Oral tacrine | Experimental | Oral tacrine Receives: Drug: Oral tacrine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Decreased cocaine-reinforced behavior
participants will make a series of choices between vouchers with an ascending monetary value and intravenous injections of cocaine
Measured: Day 9 of treatment
Secondary outcomes (1)
Changes in cocaine pharmacokinetics
Plasma levels of cocaine and metabolites will be determined by liquid chromatography-tandem mass spectrometry
Measured: Day 9 of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2011 (estimated)
- Study startOct 2012
- Primary completionSep 2013 (estimated)
- Study completionNov 2013 (estimated)
Why it stopped: One of the study medications, tacrine, is no longer clinically available
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Cocaine DependenceStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Midwest Biomedical Research
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, KENNETH GRASING, Midwest Biomedical Research
- Investigators
- Kenneth W Grasing, M.D., Principal investigator, Kansas City VA Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01406522
- Sponsor's protocol ID
- R21DA029787
- Status last verified
- Dec 2013
- First submitted
- 28 Jul 2011
- Last updated
- 18 Dec 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Grasing K, He S, Yang Y. Dose-related effects of the acetylcholinesterase inhibitor tacrine on cocaine and food self-administration in rats. Psychopharmacology (Berl). 2008 Jan;196(1):133-42. doi: 10.1007/s00213-007-0944-3. Epub 2007 Oct 5.
PubMed 17917719Grasing K, He S, Yang Y. Long-lasting decreases in cocaine-reinforced behavior following treatment with the cholinesterase inhibitor tacrine in rats selectively bred for drug self-administration. Pharmacol Biochem Behav. 2009 Nov;94(1):169-78. doi: 10.1016/j.pbb.2009.08.004. Epub 2009 Aug 19.
PubMed 19698738
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tacrine Effects on Cocaine Self-Administration and Pharmacokinetics
- ClinicalTrials.gov ID
- NCT01406522
- Acronym / sponsor ID
- R21DA029787
- Conditions
- Cocaine Dependence
- Keywords
- Acetylcholine, Cholinesterases, Cocaine, Self-Administration
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: One of the study medications, tacrine, is no longer clinically available
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Midwest Biomedical ResearchUniversity, hospital or other
- Study start
- Oct 2012
- Primary completion
- Sep 2013 (estimated)
- Study completion
- Nov 2013 (estimated)
- First posted
- 1 Aug 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
No medications are currently available for treatment of psychostimulant addiction, a compulsive preoccupation with use of cocaine and related compounds. Tacrine, a medication that is currently prescribed for Alzheimer's disease, can decrease the amount of cocaine injections that laboratory animals choose to inject by vein. This project will determine if tacrine can also decrease cocaine-motivated behavior for human subjects in a laboratory setting.
Detailed description
Background Reinforcing effects of cocaine are believed to arise through release of dopamine (DA) at the nucleus accumbens by neurons in the ventral tegmental area. Activation of cholinergic receptors on the cell bodies of these neurons can enhance DA release. Elevated levels of acetylcholine (ACh) in the nucleus accumbens may also serve to inhibit appetitive behaviors. Cholinesterase inhibitors such as tacrine increase synaptic levels of ACh by preventing its inactivation by acetylcholinesterase (AChE) or butyrylcholinesterase (BuChE), and can improve learning and memory. In animals, cholinesterase inhibitors can attenuate cocaine self-administration and conditioned place preference. Tacrine is a centrally acting, reversible inhibitor of AChE and BuChE that is approved for treatment of Alzheimer's disease. In addition to its effects on the cholinergic system, tacrine can potentiate the actions of monoamines, including DA. Although use of tacrine has declined because of requirements for monitoring of potential liver toxicity and pharmacokinetics that necessitate multiple daily doses, it is more potent than other cholinesterase inhibitors in attenuating cocaine self-administration in animals. Pretreatment with tacrine can produce long-lasting reductions in cocaine-reinforced behavior in rats, described as persistent attenuation (cocaine self-administration is decreased by more than 80% over a period of three days during which no additional cholinesterase inhibitor is administered, see Figure 1). No previous studies have evaluated whether tacrine can modify the effects of cocaine in humans.
Rationale To our knowledge, tacrine is the only compound that can produce persistent attenuation in rats treated with clinically relevant doses. If similar effects were observed in humans, this would lead to an important paradigm shift for substance abuse treatment, in that large reductions in cocaine-reinforced behavior could be produced without the need for continuous dosing with a medication. This scenario could remove the requirement for continued compliance with oral dosing in some patients with its associated potential for toxicity.
Specific Aims:
- Evaluate whether tacrine treatment causes persistent attenuation of cocaine-reinforced behavior in humans.
- Determine the effectiveness of pretreatment with tacrine in attenuating cocaine-induced craving.
- Evaluate plasma levels of cocaine and characterize the bioavailability of tacrine in individual patients.
Methods This is a randomized, double-blind, double-dummy, placebo-controlled, inpatient, single-center, parallel-group evaluation of the potential for oral tacrine to modify cocaine self-administration, cocaine-induced craving, and the pharmacokinetics of cocaine and tacrine. To evaluate the occurrence of persistent attenuation, the subjective and reinforcing effects of intravenous cocaine will be determined during oral treatment and three days following its discontinuation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Oral placebo | Placebo comparator | Drug: Oral placeboInactive treatment |
| Oral tacrine | Experimental | Drug: Oral tacrineOral tacrine |
Who may qualify
- Ages
- 21 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Meets DSM-IV-TR criteria for cocaine abuse or dependence, with at least one cocaine-positive urine specimen within the six weeks prior to enrollment.
- Has used cocaine for a duration of at least 6 months, with at least weekly use during the last 30 days by a rapid route of administration (either smoked or intravenous injection).
- Is male or female, between 21 and 50 years old.
Key exclusion criteria (3 listed)
- Has a history of a medical adverse reaction to cocaine or other psychostimulants, including loss of consciousness, chest pain, cardiac ischemia, or seizure.
- Has any current Axis I psychiatric disorder other than drug abuse or dependence.
- Meets DSM-IV-TR criteria for dependence on opiates, benzodiazepines, alcohol, or other sedative-hypnotics.
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 |
|---|---|---|
| Oral tacrineTacrine, 160 mg per day, four times daily | Drug | Oral tacrine |
| Oral placeboMicrocrystalline cellulose | Drug | Oral placebo |
Primary outcome
Decreased cocaine-reinforced behavior
Time frame: Day 9 of treatment
participants will make a series of choices between vouchers with an ascending monetary value and intravenous injections of cocaine
1 secondary outcome
Changes in cocaine pharmacokinetics
Time frame: Day 9 of treatment
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2013.
- Background: PubMed 17917719Grasing K, He S, Yang Y. Dose-related effects of the acetylcholinesterase inhibitor tacrine on cocaine and food self-administration in rats. Psychopharmacology (Berl). 2008 Jan;196(1):133-42. doi: 10.1007/s00213-007-0944-3. Epub 2007 Oct 5.
- Background: PubMed 19698738Grasing K, He S, Yang Y. Long-lasting decreases in cocaine-reinforced behavior following treatment with the cholinesterase inhibitor tacrine in rats selectively bred for drug self-administration. Pharmacol Biochem Behav. 2009 Nov;94(1):169-78. doi: 10.1016/j.pbb.2009.08.004. Epub 2009 Aug 19.
Related trials for Cocaine Dependence
Recruiting
rTMS and Cognitive-behavioral Therapy for Cocaine Use Disorder
Cocaine Use, Cocaine Dependence
Not yet recruiting
QAIAx - SGI/SI Smart Health Cities: Microcity Enclave Program (Quantum SI/AGI Agency a/k/a AI City Hall Project - UPSTO App Nos. 64/074,526, 64/063,557, 64/105,164, 63/903,181, 63/729,428, 64/125,360; USPTO EO 9424 Assignment ID: 2101042 / ARN: REEL/FRAME: 76481/0026 - OUSD-R&E, Department of War)
Asperger's Disorder, Asperger Disorder
Recruiting
Transcranial Direct Current Stimulation (tDCS) for Treatment of Substance Use Disorder
Cocaine Use Disorder, Cocaine Dependence
RecruitingPhase 1
Safety Study of a Disrupted Adenovirus (Ad) Serotype Cocaine Vaccine for Cocaine-dependent Individuals
Cocaine Dependence
Active, not recruitingPhase 1
AAV8-hCocH for Cocaine Use Disorder
Cocaine Dependence, in Remission
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.
Kenneth W Grasing, M.D. principal investigator
Kansas City VA Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Oral tacrine in people with Cocaine Dependence, run by Midwest Biomedical Research 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 3 inclusion and 3 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: withdrawn, as of the sponsor's last update on 18 Dec 2013. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Decreased cocaine-reinforced behavior (time frame: Day 9 of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01406522, which also lists 2 linked publications.
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 18 Dec 2013.