Lorcaserin Intra Venous Cocaine Effects

NCT ID: NCT02680288

Last Updated: 2016-03-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1/PHASE2

Total Enrollment

32 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-11-30

Study Completion Date

2019-11-30

Brief Summary

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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

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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:

1. Evaluate whether lorcaserin treatment attenuates the positive subjective effects of cocaine and drug-reinforced behavior.
2. 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

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Cocaine Use Disorders

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Outcome Assessors

Study Groups

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Oral Placebo

Oral inert treatment

Group Type PLACEBO_COMPARATOR

Oral Placebo

Intervention Type OTHER

Oral inert treatment

Active Treatment, Low-Dose

Lorcaserin 10 mg, single dose

Group Type EXPERIMENTAL

Lorcaserin, 10 mg

Intervention Type DRUG

Oral type 2C serotonergic agonist, low-dose

Active Treatment, High-Dose

Lorcaserin 20 mg, single dose

Group Type EXPERIMENTAL

Lorcaserin, 20 mg

Intervention Type DRUG

Oral type 2C serotonergic agonist, high-dose

Interventions

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Lorcaserin, 10 mg

Oral type 2C serotonergic agonist, low-dose

Intervention Type DRUG

Lorcaserin, 20 mg

Oral type 2C serotonergic agonist, high-dose

Intervention Type DRUG

Oral Placebo

Oral inert treatment

Intervention Type OTHER

Other Intervention Names

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Belviq Belviq

Eligibility Criteria

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Inclusion Criteria

1. Is non-treatment-seeking and has used cocaine regularly for at least six months.
2. 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.
3. Is male or female, between 21 and 50 years old.
4. Is able to verbalize understanding of the consent form, able to provide written informed consent, and verbalize willingness to complete study procedures.
5. Is agreeable to the study schedule and likely to complete all interventions and measures.
6. Has a medical history, physical exam, and screening laboratory results that demonstrate no contraindication to participation.

Exclusion Criteria

1. Has a history of a medical adverse reaction to cocaine or other psycho stimulants, including loss of consciousness, chest pain, cardiac ischemia, or seizure.
2. Has any current Axis I psychiatric disorder other than drug abuse or dependence.
3. Meets DSM-IV-TR criteria for dependence on opiates, benzodiazepines, alcohol, or other sedative-hypnotics.
4. Has received opiate-substitution therapy within two months prior to enrollment.
5. 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.
6. Has a diagnosis of adult asthma or chronic obstructive pulmonary disease.
7. Has had head trauma that resulted in neurological sequelae (e.g., loss of memory for greater than 5 minutes).
8. Has a history of valvular heart disease, congestive heart failure, syncope, bradycardia, or any other cardiac condition.
9. 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).
10. 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).
11. 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).
12. Currently being treated for erectile dysfunction.
13. Has an unstable medical condition, which, in the judgment of investigators, would make participation hazardous, such as AIDS or active TB.
14. 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.
15. Has current suicidal ideation as assessed by the SCID interview.
16. Has clinically significant ECG abnormalities, including QTc interval prolongation \> 450 milliseconds in men or 480 milliseconds in women.
17. Has donated blood or participated in another clinical trial within 4 weeks of enrollment.
18. In the opinion of investigators, is expected to fail to complete the study protocol due to probable incarceration or relocation from the clinic area.
19. Has had known or suspected hypersensitivity to Lorcaserin.
20. Is currently being treated with an adrenergic receptor antagonist ('beta blocker').
21. Is currently receiving Lorcaserin, potential CYP2D substrates, or medications associated with the serotonin syndrome or neuroleptic-malignant syndrome (see Tables 8 and 9).
22. Has a significant potential for violent behavior, as assessed by the Structured Assessment of Violence Risk in Youth (SAVRY).23
Minimum Eligible Age

21 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Midwest Biomedical Research Foundation

OTHER

Sponsor Role lead

Responsible Party

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KENNETH GRASING

Staff Physician

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Kenneth W Grasing, MD

Role: PRINCIPAL_INVESTIGATOR

Midwest Biomedical Research Foundation

Locations

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Kansas City VA Medical Center

Kansas City, Missouri, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Midwest Biomedical Research Foundation KCVA

Role: CONTACT

(816) 499-1614

Facility Contacts

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Kenneth W Grasing, M.D.

Role: primary

816-922-2756

References

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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.

Reference Type BACKGROUND
PMID: 14627998 (View on PubMed)

Cunningham 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.

Reference Type BACKGROUND
PMID: 21575646 (View on PubMed)

Pirtle 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.

Reference Type DERIVED
PMID: 30811963 (View on PubMed)

Other Identifiers

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MIRB#0016

Identifier Type: -

Identifier Source: org_study_id

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