Cocaine Use DisordersPhase 1/2LIVENCT02680288
Lorcaserin Intra Venous Cocaine Effects
A Phase 1/2 study testing Lorcaserin, 10 mg and Lorcaserin, 20 mg in people with Cocaine Use Disorders, run by Midwest Biomedical Research at 1 site in United States.
Trial summary
This is a randomized, cross-over, single-blind, placebo-controlled, single-center, multiple-panel evaluation of the potential for oral lorcaserin to modify cocaine self-administration in a laboratory setting. Read more about this study
- Who is it for?
- Ages 21 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Cocaine Use Disorders
- What is being tested?
- Lorcaserin, 10 mg and Lorcaserin, 20 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2015to Nov 2019
- Phase
- Phase 1/2
- 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
- Healthy volunteers accepted
- Adult
Who may be able to join
- Is non-treatment-seeking and has used cocaine regularly for at least six months.
- Has used cocaine by a rapid route of administration (smoked or intravenous injection), at least three times per week, for three of the preceding six weeks.
- Is male or female, between 21 and 50 years old.
- Is able to verbalize understanding of the consent form, able to provide written informed consent, and verbalize willingness to complete study procedures.
- Is agreeable to the study schedule and likely to complete all interventions and measures.
- Has a medical history, physical exam, and screening laboratory results that demonstrate no contraindication to participation.
Who cannot join
- Has a history of a medical adverse reaction to cocaine or other psycho stimulants, 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.
- Has received opiate-substitution therapy within two months prior to enrollment.
- Has a current or past history of seizure disorder other than febrile seizures, including alcohol- or psycho stimulant- related seizures, or family history of seizure disorder.
- Has a diagnosis of adult asthma or chronic obstructive pulmonary disease.
Show all 22Show fewer
- Has had head trauma that resulted in neurological sequelae (e.g., loss of memory for greater than 5 minutes).
- Has a history of valvular heart disease, congestive heart failure, syncope, bradycardia, or any other cardiac condition.
- Has a condition that increases the risk of cocaine-induced hypertension or ischemic heart disease, such as hypertension, hypercholesterolemia, renal disease (serum creatinine > 1.4 mg/dl), diabetes (fasting glucose level ≥ 100 mg/dl).
- Has a history of jaundice, hepatitis, or laboratory evidence of hepatic insufficiency (total bilirubin ≥ 2.0, serum albumin ≤ 3.5 gm./dl); or current abnormalities of liver function testing with serologic evidence of hepatitis (serology and coagulation will be evaluated in individuals with aspartate transaminase or Alaine aminotransferase > 40 IU/L).
- History of priapism or conditions that would predispose to priapism (sickle cell anemia, multiple myeloma, leukemia, Peyronie's disease, or other anatomical deformation of the penis).
- Currently being treated for erectile dysfunction.
- Has an unstable medical condition, which, in the judgment of investigators, would make participation hazardous, such as AIDS or active TB.
- If female, is pregnant or lactating (nursing), not practicing adequate methods of contraception, or planning to become pregnant within one month of conclusion of the study.
- Has current suicidal ideation as assessed by the SCID interview.
- Has clinically significant ECG abnormalities, including QTc interval prolongation > 450 milliseconds in men or 480 milliseconds in women.
- Has donated blood or participated in another clinical trial within 4 weeks of enrollment.
- In the opinion of investigators, is expected to fail to complete the study protocol due to probable incarceration or relocation from the clinic area.
- Has had known or suspected hypersensitivity to Lorcaserin.
- Is currently being treated with an adrenergic receptor antagonist ('beta blocker').
- Is currently receiving Lorcaserin, potential CYP2D substrates, or medications associated with the serotonin syndrome or neuroleptic-malignant syndrome (see Tables 8 and 9).
- Has a significant potential for violent behavior, as assessed by the Structured Assessment of Violence Risk in Youth (SAVRY).23
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
Kansas City VA Medical Center
Kansas City, Missouri, 64128
Kenneth W Grasing, M.D., 816-922-2756, kenneth.grasing@va.gov
Kenneth W Grasing, M.D.
About this study
Official title: Lorcaserin Effects on Cocaine Craving and Drug-Reinforced Behavior
This is a randomized, cross-over, single-blind, placebo-controlled, single-center, multiple-panel evaluation of the potential for oral lorcaserin to modify cocaine self-administration in a laboratory setting. To prevent unauthorized drug use, study medications will be administered as participants are confined during overnight stays at the Medical Center. Non-treatment-seeking, regular cocaine users will receive oral treatment with single doses of placebo, lorcaserin 10 mg (Panel 1), or lorcaserin 20 mg (Panel 2). Afterwards, the subjective and reinforcing effects of intravenous cocaine will be measured in a laboratory setting.
Read the detailed description
Background
Serotonin (5-HT) is one of three brain monoamines that are widely distributed in the brain and play important roles in affect and goal-directed behaviors. Limbic structures that underlie behavior motivated by palatable food and drugs of abuse receive dense projections from brainstem serotonergic nuclei. In rats, light and sound cues associated with access to cocaine strongly stimulate drug-seeking behavior. Agonists for the type 2C serotonergic receptor (5-HT₂cR) attenuate this responding.8 Drug taking (cocaine self-administration) is also attenuated at 5-HT₂cR agonist doses similar to those that decrease food-reinforced responding and cause reductions in locomotor activity.
Lorcaserin is a novel and selective agonist of the 5-HT₂cR recently approved by the FDA for weight loss therapy. It acts selectively at this receptor subtype with minimal activation of 5-HT₂ᴀR or 5-HT₂ᴃR receptors. Based on initial clinical studies leading to its approval, lorcaserin is well tolerated and probably does not cause cardiac valve disease or other serious side effects. Even so, given the potential for serious adverse events, the FDA has limited its use to patients who are either obese or overweight with a medical complication such as hypertension. Whether or not lorcaserin will become generally accepted as a long-term treatment for obesity will depend on the results of ongoing post-marketing studies of cardiovascular outcome data.
Rationale In preclinical studies, agonists for the 5-HT₂cR potently attenuate cocaine-seeking behavior. Lorcaserin is a recently approved selective 5-HT₂cR agonist with an acceptable safety profile in humans. No published studies have reported its effects on cocaine-induced craving or drug-reinforced responding in humans.
Specific Aims:
- Evaluate whether lorcaserin treatment attenuates the positive subjective effects of cocaine and drug-reinforced behavior.
- Determine whether active treatment modifies cocaine- or script- induced craving.
Methods This is a randomized, cross-over, double-blind, placebo-controlled, single-center, multiple-panel evaluation of the potential for oral lorcaserin to modify cocaine self-administration in a laboratory setting. Up to 32 non-treatment-seeking, regular cocaine users will receive treatment with single doses of oral placebo, lorcaserin 10 mg (Panel 1), or lorcaserin 20 mg (Panel 2). Script-guided imagery of autobiographical memories will be developed based on experiences related to cocaine use, anger, and a neutral event. Following treatment with lorcaserin, script-induced emotional states will be assayed. Sampling doses of cocaine (0.0, 0.23, and 0.46 mg/kg) will be administered, and participants will choose between self-administering additional intravenous doses or receiving monetary alternatives. Detailed measures of the negative and positive subjective effects of intravenous infusions will also be made. As noncontingent infusions of cocaine are administered, the pharmacokinetics of cocaine and lorcaserin will be determined.
- Conditions
- Cocaine Use Disorders
- Being tested
- Lorcaserin, 10 mg, Lorcaserin, 20 mg, Oral Placebo
- Keywords
- Psychostimulant, Craving, Cocaine.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lorcaserin, 10 mgDrug
Also called Belviq
Oral type 2C serotonergic agonist, low-dose
Lorcaserin, 20 mgDrug
Also called Belviq
Oral type 2C serotonergic agonist, high-dose
Oral PlaceboOther
Oral inert treatment
| Study group | Role | What they receive |
|---|---|---|
| Oral Placebo | Placebo comparator | Oral inert treatment Receives: Other: Oral Placebo |
| Active Treatment, Low-Dose | Experimental | Lorcaserin 10 mg, single dose Receives: Drug: Lorcaserin, 10 mg |
| Active Treatment, High-Dose | Experimental | Lorcaserin 20 mg, single dose Receives: Drug: Lorcaserin, 20 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cocaine-Induced 'High'
Visual analogue scale rating of 'high' after receiving cocaine
Measured: Day 1 of Lorcaserin Treatment
Secondary outcomes (1)
Cocaine-Induced Craving
Visual analogue scale rating of 'How much do you WANT to use cocaine' after receiving intravenous cocaine
Measured: Day 1 of Lorcaserin treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2016 (estimated)
- Study startNov 2015
- Primary completionSep 2018 (estimated)
- Study completionNov 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Cocaine Use DisordersStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 32 participants (estimated)
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, MD, Principal investigator, Midwest Biomedical Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02680288
- Sponsor's protocol ID
- MIRB#0016
- Acronym
- LIVE
- Status last verified
- Mar 2016
- First submitted
- 5 Feb 2016
- Last updated
- 18 Mar 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Burmeister JJ, Lungren EM, Kirschner KF, Neisewander JL. Differential roles of 5-HT receptor subtypes in cue and cocaine reinstatement of cocaine-seeking behavior in rats. Neuropsychopharmacology. 2004 Apr;29(4):660-8. doi: 10.1038/sj.npp.1300346.
PubMed 14627998Cunningham KA, Fox RG, Anastasio NC, Bubar MJ, Stutz SJ, Moeller FG, Gilbertson SR, Rosenzweig-Lipson S. Selective serotonin 5-HT(2C) receptor activation suppresses the reinforcing efficacy of cocaine and sucrose but differentially affects the incentive-salience value of cocaine- vs. sucrose-associated cues. Neuropharmacology. 2011 Sep;61(3):513-23. doi: 10.1016/j.neuropharm.2011.04.034. Epub 2011 May 11.
PubMed 21575646Pirtle JL, Hickman MD, Boinpelly VC, Surineni K, Thakur HK, Grasing KW. The serotonin-2C agonist Lorcaserin delays intravenous choice and modifies the subjective and cardiovascular effects of cocaine: A randomized, controlled human laboratory study. Pharmacol Biochem Behav. 2019 May;180:52-59. doi: 10.1016/j.pbb.2019.02.010. Epub 2019 Feb 24.
PubMed 30811963
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lorcaserin Effects on Cocaine Craving and Drug-Reinforced Behavior
- ClinicalTrials.gov ID
- NCT02680288
- Acronym / sponsor ID
- LIVE / MIRB#0016
- Conditions
- Cocaine Use Disorders
- Keywords
- Psychostimulant, Craving, Cocaine.
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 32 participants (estimated)
- Lead sponsor
- Midwest Biomedical ResearchUniversity, hospital or other
- Study start
- Nov 2015
- Primary completion
- Sep 2018 (estimated)
- Study completion
- Nov 2019 (estimated)
- First posted
- 11 Feb 2016 (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.
This is a randomized, cross-over, single-blind, placebo-controlled, single-center, multiple-panel evaluation of the potential for oral lorcaserin to modify cocaine self-administration in a laboratory setting. To prevent unauthorized drug use, study medications will be administered as participants are confined during overnight stays at the Medical Center. Non-treatment-seeking, regular cocaine users will receive oral treatment with single doses of placebo, lorcaserin 10 mg (Panel 1), or lorcaserin 20 mg (Panel 2). Afterwards, the subjective and reinforcing effects of intravenous cocaine will be measured in a laboratory setting.
Detailed description
Background
Serotonin (5-HT) is one of three brain monoamines that are widely distributed in the brain and play important roles in affect and goal-directed behaviors. Limbic structures that underlie behavior motivated by palatable food and drugs of abuse receive dense projections from brainstem serotonergic nuclei. In rats, light and sound cues associated with access to cocaine strongly stimulate drug-seeking behavior. Agonists for the type 2C serotonergic receptor (5-HT₂cR) attenuate this responding.8 Drug taking (cocaine self-administration) is also attenuated at 5-HT₂cR agonist doses similar to those that decrease food-reinforced responding and cause reductions in locomotor activity.
Lorcaserin is a novel and selective agonist of the 5-HT₂cR recently approved by the FDA for weight loss therapy. It acts selectively at this receptor subtype with minimal activation of 5-HT₂ᴀR or 5-HT₂ᴃR receptors. Based on initial clinical studies leading to its approval, lorcaserin is well tolerated and probably does not cause cardiac valve disease or other serious side effects. Even so, given the potential for serious adverse events, the FDA has limited its use to patients who are either obese or overweight with a medical complication such as hypertension. Whether or not lorcaserin will become generally accepted as a long-term treatment for obesity will depend on the results of ongoing post-marketing studies of cardiovascular outcome data.
Rationale In preclinical studies, agonists for the 5-HT₂cR potently attenuate cocaine-seeking behavior. Lorcaserin is a recently approved selective 5-HT₂cR agonist with an acceptable safety profile in humans. No published studies have reported its effects on cocaine-induced craving or drug-reinforced responding in humans.
Specific Aims:
- Evaluate whether lorcaserin treatment attenuates the positive subjective effects of cocaine and drug-reinforced behavior.
- Determine whether active treatment modifies cocaine- or script- induced craving.
Methods This is a randomized, cross-over, double-blind, placebo-controlled, single-center, multiple-panel evaluation of the potential for oral lorcaserin to modify cocaine self-administration in a laboratory setting. Up to 32 non-treatment-seeking, regular cocaine users will receive treatment with single doses of oral placebo, lorcaserin 10 mg (Panel 1), or lorcaserin 20 mg (Panel 2). Script-guided imagery of autobiographical memories will be developed based on experiences related to cocaine use, anger, and a neutral event. Following treatment with lorcaserin, script-induced emotional states will be assayed. Sampling doses of cocaine (0.0, 0.23, and 0.46 mg/kg) will be administered, and participants will choose between self-administering additional intravenous doses or receiving monetary alternatives. Detailed measures of the negative and positive subjective effects of intravenous infusions will also be made. As noncontingent infusions of cocaine are administered, the pharmacokinetics of cocaine and lorcaserin will be determined.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Oral Placebo | Placebo comparator | Other: Oral PlaceboOral inert treatment |
| Active Treatment, Low-Dose | Experimental | Drug: Lorcaserin, 10 mgLorcaserin 10 mg, single dose |
| Active Treatment, High-Dose | Experimental | Drug: Lorcaserin, 20 mgLorcaserin 20 mg, single dose |
Who may qualify
- Ages
- 21 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Is non-treatment-seeking and has used cocaine regularly for at least six months.
- Has used cocaine by a rapid route of administration (smoked or intravenous injection), at least three times per week, for three of the preceding six weeks.
- Is male or female, between 21 and 50 years old.
- Is able to verbalize understanding of the consent form, able to provide written informed consent, and verbalize willingness to complete study procedures.
- Is agreeable to the study schedule and likely to complete all interventions and measures.
Key exclusion criteria (22 listed)
- Has a history of a medical adverse reaction to cocaine or other psycho stimulants, 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.
- Has received opiate-substitution therapy within two months prior to enrollment.
- Has a current or past history of seizure disorder other than febrile seizures, including alcohol- or psycho stimulant- related seizures, or family history of seizure disorder.
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 |
|---|---|---|
| Lorcaserin, 10 mgAlso: BelviqOral type 2C serotonergic agonist, low-dose | Drug | Active Treatment, Low-Dose |
| Lorcaserin, 20 mgAlso: BelviqOral type 2C serotonergic agonist, high-dose | Drug | Active Treatment, High-Dose |
| Oral PlaceboOral inert treatment | Other | Oral Placebo |
Primary outcome
Cocaine-Induced 'High'
Time frame: Day 1 of Lorcaserin Treatment
Visual analogue scale rating of 'high' after receiving cocaine
1 secondary outcome
Cocaine-Induced Craving
Time frame: Day 1 of Lorcaserin treatment.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Mar 2016.
- Background: PubMed 14627998Burmeister JJ, Lungren EM, Kirschner KF, Neisewander JL. Differential roles of 5-HT receptor subtypes in cue and cocaine reinstatement of cocaine-seeking behavior in rats. Neuropsychopharmacology. 2004 Apr;29(4):660-8. doi: 10.1038/sj.npp.1300346.
- Background: PubMed 21575646Cunningham KA, Fox RG, Anastasio NC, Bubar MJ, Stutz SJ, Moeller FG, Gilbertson SR, Rosenzweig-Lipson S. Selective serotonin 5-HT(2C) receptor activation suppresses the reinforcing efficacy of cocaine and sucrose but differentially affects the incentive-salience value of cocaine- vs. sucrose-associated cues. Neuropharmacology. 2011 Sep;61(3):513-23. doi: 10.1016/j.neuropharm.2011.04.034. Epub 2011 May 11.
- Derived from this study: PubMed 30811963Pirtle JL, Hickman MD, Boinpelly VC, Surineni K, Thakur HK, Grasing KW. The serotonin-2C agonist Lorcaserin delays intravenous choice and modifies the subjective and cardiovascular effects of cocaine: A randomized, controlled human laboratory study. Pharmacol Biochem Behav. 2019 May;180:52-59. doi: 10.1016/j.pbb.2019.02.010. Epub 2019 Feb 24.
- Individual participant dataSharing planned: No
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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.
Kenneth W Grasing, MD principal investigator
Midwest Biomedical Research
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Lorcaserin, 10 mg and Lorcaserin, 20 mg in people with Cocaine Use Disorders, 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 6 inclusion and 22 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: status not confirmed, as of the sponsor's last update on 18 Mar 2016. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Midwest Biomedical Research Foundation KCVA ((816) 499-1614, Kenneth.Grasing@va.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cocaine-Induced 'High' (time frame: Day 1 of Lorcaserin 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 NCT02680288, which also lists 3 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 Mar 2016.