Cocaine and Zolmitriptan

Cocaine Use Disorder Clinical Trial

Official title:

Behavioral Effects of Drugs (Inpatient): 42 (Cocaine and Zolmitriptan)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05019430
• Other study ID #: BED In 42
• Secondary ID: R01DA052203
• Status: Recruiting
• Phase: Early Phase 1
• Start date: October 15, 2021
• Est. completion date: July 31, 2024

Study information

• Verified date: December 2023
• Source: University of Kentucky
• Contact: William W Stoops, PhD
• Phone: 859-257-5388
• Email: william.stoops[@]uky.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Cocaine potently inhibits the reuptake of serotonin (5-HT). Increased synaptic 5-HT resulting from this reuptake inhibition activates multiple 5-HT receptor subtypes. Some of these receptor subtypes have been implicated in the abuse-related effects of cocaine, including its primary reinforcing effects (i.e., cocaine taking behavior). 5-HT1b receptors, which are autoreceptors on 5-HT nerve endings that regulate 5-HT release and heteroreceptors that also mediate other neurotransmitter release, play a particularly important role in cocaine effects, likely because they are highly expressed in the mesocorticolimbic system. The 5-HT1b system displays profound dysregulation during both active cocaine use and abstinence. Initial preclinical research showed that selective 5-HT1b agonists enhanced the reinforcing and locomotor effects of cocaine during ongoing cocaine administration, but subsequent research showed that these agents robustly attenuated reinstatement of cocaine- and cue-primed cocaine seeking behavior. These findings have been replicated in rigorously conducted studies using multiple schedules of reinforcement and negative sucrose reinforcement controls across laboratories. Notably, though, these preclinical studies used compounds not approved for use in humans, hindering translation. Recently published data show that zolmitriptan, a commercially available selective 5-HT1b agonist migraine medication, also selectively attenuates the reinforcing and other abuse-related effects of cocaine, regardless of stage of use (i.e., ongoing or extinguished cocaine self-administration). Although a robust preclinical literature supports the premise that 5-HT1b activation reduces a number of cocaine-associated behaviors (e.g., self-administration, cocaine seeking), this area remains unstudied in humans. The overarching goal of this project is to advance these promising preclinical findings, specifically those with zolmitriptan, to a clinical population, thereby demonstrating that the 5-HT1b system plays a key role in the effects of cocaine in humans

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: July 31, 2024
• Est. primary completion date: July 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Recent cocaine use

Exclusion Criteria:

• Abnormal screening outcome (e.g., ECG, blood chemistry result) that study physicians deem clinically significant
• Current or past histories of substance use disorder that are deemed by the study physicians to interfere with study completion
• History of serious physical disease, current physical disease, impaired cardiovascular functioning, chronic obstructive pulmonary disease, history of seizure or current or past histories of serious psychiatric disorder that in the opinion of the study physician would interfere with study participation will be excluded from participation
• Females not currently using effective birth control
• Contraindications to cocaine or zolmitriptan

Related Conditions & MeSH terms

• Cocaine Use Disorder

Intervention

Drug:
• Cocaine
The pharmacodynamic effects of cocaine will be determined during maintenance on placebo and zolmitriptan.
• Placebo oral capsule
The pharmacodynamic effects of placebo will be determined.
• Zolmitriptan
The pharmacodynamic effects of zolmitriptan maintenance will be determined.

Locations

Country	Name	City	State
United States	University of Kentucky	Lexington	Kentucky

Sponsors (2)

Lead Sponsor	Collaborator
William Stoops	National Institute on Drug Abuse (NIDA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Reinforcing Effects of Cocaine Following Placebo Maintenance.	Number of cocaine doses earned by subjects on a progressive ratio schedule of reinforcement.	Following at least 3 days of maintenance on placebo during inpatient admission
Primary	Reinforcing Effects of Cocaine Following Zolmitriptan Dose 1 Maintenance.	Number of cocaine doses earned by subjects on a progressive ratio schedule of reinforcement.	Following at least 3 days of maintenance on zolmitriptan dose 1 during inpatient admission.
Primary	Reinforcing Effects of Cocaine Following Zolmitriptan Dose 2 Maintenance.	Number of cocaine doses earned by subjects on a progressive ratio schedule of reinforcement.	Following at least 3 days of maintenance on zolmitriptan dose 2 during inpatient admission.
Primary	Reinforcing Effects of Cocaine Following Zolmitriptan Dose 3 Maintenance.	Number of cocaine doses earned by subjects on a progressive ratio schedule of reinforcement.	Following at least 3 days of maintenance on zolmitriptan dose 3 during inpatient admission.
Secondary	Adjective Rating Scale-Sedative	Subjects will complete the adjective rating scale during 12 sessions while they are admitted to our inpatient unit. Responses to 16 items are summed (total score=0-64; Higher values=more sedation) to calculate scores on a sedative subscale.	12 times over approximately 1 month inpatient admission
Secondary	Adjective Rating Scale-Stimulant	Subjects will complete the adjective rating scale during 12 sessions while they are admitted to our inpatient unit. Responses to 16 items are summed (total score=0-64; Higher values=more sedation) to calculate scores on a stimulant subscale.	12 times over approximately 1 month inpatient admission
Secondary	Drug Effect Questionnaire	Subjects will complete the drug effect questionnaire during 12 sessions while they are admitted to our inpatient unit. The items (total scores=0-100; Higher scores=greater drug effect) on this scale categorize the constellation of drug effects endorsed by subjects.	12 times over approximately 1 month inpatient admission
Secondary	Heart rate	Beats per minute. Measured daily during inpatient admission.	Daily over approximately four week inpatient admissions
Secondary	Blood pressure	mmHg. Measured daily during inpatient admission.	Daily over approximately 1 month inpatient admission.
Secondary	Temperature	Degrees fahrenheit. Measured daily during inpatient admission.	Daily over approximately 1 month inpatient admission
Secondary	Side Effects	Subjects will complete a side effects questionnaire daily while they reside on the inpatient unit. Side Effects questions will query subjects about common effects of centrally active medications.	Daily over approximately 1 month inpatient admission
Secondary	Delay Discounting Task	Subjects will complete the delay discounting task during 12 sessions while they are admitted to our inpatient unit. Responses will be used to calculate discounting slope (i.e., K).	12 times over approximately 1 month inpatient admission
Secondary	n-back Task	Subjects will complete the n-back task during 12 sessions while they are admitted to our inpatient unit. Percentage of correct responses will be the outcome.	12 times over approximately 1 month inpatient admission
Secondary	Stop-Signal Task Reaction Time	Subjects will complete the stop-signal task during 12 sessions while they are admitted to our inpatient unit. Reaction time in milliseconds and proportion of inhibitory failures will be the outcome variables.	12 times over approximately 1 month inpatient admission
Secondary	Stop-Signal Task Inhibitory Failures	Subjects will complete the stop-signal task during 12 sessions while they are admitted to our inpatient unit. Proportion of inhibitory failures will be the outcome variable.	12 times over approximately 1 month inpatient admission