Clinical trial NCT05505630: The Effects of Sedatives on Tobacco Use Disorder Version 2
Official title: The Effects of Sedatives on Tobacco Use Disorder Version 2
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Tobacco Smoking
Keywords: nicotine addiction
smoking
placebo
sedatives
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: Nida Addiction Research Center
First posted: 2022-08-18
Enrollment: 52
Sex: ALL
Minimum age (years): 21
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: Double-blind, placebo-controlled, randomized mechanistic clinical trial to test an intravenous dose of either ketamine, midazolam, dexmedetomidine, or a placebo (saline) on cigarette smoking behavior, craving, and neural effects.

Detailed description: This double-blind, placebo-controlled, randomized mechanistic clinical trial will test non-treatment seeking smokers with an intravenous infusion of ketamine (0.71 mg/kg), midazolam (0.025 mg/kg), dexmedetomidine (0.025 mg/kg), or placebo, at least 2 weeks apart. Participants will complete 7-day ecological momentary assessment (EMA) of daily craving, withdrawal, and smoking behavior before and after each infusion. They will be asked to abstain from tobacco/nicotine for twenty-four hours post-infusion to induce withdrawal symptoms and return to the lab the following day to complete measures of craving, withdrawal, an MRI scan, and smoking latency. After this study visit, participants will be allowed to smoke as usual for the rest of the EMA diary period. Physical and subjective effects and adverse effects will be closely monitored throughout.

Eligibility criteria: Inclusion Criteria:

* Smokes cigarettes daily for at least 2 years
* Afternoon expired breath carbon monoxide at least 5 ppm or morning urinary cotinine at least 100 ng/ml
* Negative urine drug screen for psychoactive drugs and negative breath alcohol

Exclusion Criteria:

* Have an unstable medical condition or stable medical condition that would interact with study drug or participation, including chronic pulmonary disease, coronary artery disease, current brain tumor, current increased intracranial pressure or impaired consciousness
* History of serious head trauma or neurological disorder (e.g., seizure disorder)
* Have any of the following: hypertension (i.e., systolic \>140 mm Hg and/or diastolic \>90 mm Hg on three separate measures; systolic \>170 or diastolic \> 110 on any occasion), pre-existing severe gastrointestinal narrowing (pathologic or iatrogenic).
* Use of drugs that would interact with study drug or increase risk of adverse events
* Among women, pregnancy or lactation

Primary outcomes:
measure: Difference in craving between drug and placebo
timeFrame: 24-hours post infusion
measure: Difference in tobacco withdrawal symptoms
timeFrame: 24-hours post infusion
measure: Difference in cigarette demand
timeFrame: 24-hours post infusion
measure: Number of cigarettes smoked ad lib
timeFrame: 24-hours post infusion
Secondary outcomes:
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: Merideth A Addicott, MD
role: PRINCIPAL_INVESTIGATOR
References: