The Effects of Sedatives on Tobacco Use Disorder Version 2

Early Phase 1

Recruiting

• Conditions: Tobacco Smoking
• Interventions: Drug: Midazolam; Drug: Ketamine; Drug: Dexmedetomidine; Drug: Saline

• Registration Number: NCT05505630
• Lead Sponsor: Wake Forest University Health Sciences

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.

Study Timeline

• Study First Submitted: 2022-08-15
• Study First Submitted QC: 2022-08-15
• Study First Posted: 2022-08-18
• Study Start: 2023-01-31
• Status Verified: 2024-07
• Last Update Submitted: 2025-01-09
• Last Update Posted: 2025-01-13
• Primary Completion: 2025-12
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 52

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Saline first injection; midazolam second injection	Saline	Subjects in this arm will receive a single intravenous infusion of placebo at the first injection visit and a single intravenous infusion midazolam at the second injection visit
Saline first injection; dexmedetomidine second injection	Saline	Subjects in this arm will receive a single intravenous infusion of placebo at the first injection visit and a single intravenous infusion dexmedetomidine at the second injection visit.
Saline first injection; ketamine second injection	Saline	Subjects in this arm will receive a single intravenous infusion of placebo at the first injection visit and a single intravenous infusion ketamine at the second injection visit.
Ketamine first injection; Saline second injection	Saline	Subjects in this arm will receive a single intravenous infusion of ketamine at the first injection visit and a single intravenous infusion placebo at the second injection visit.
Saline first injection; midazolam second injection	Midazolam	Subjects in this arm will receive a single intravenous infusion of placebo at the first injection visit and a single intravenous infusion midazolam at the second injection visit
Midazolam first injection; Saline second injection	Saline	Subjects in this arm will receive a single intravenous infusion of midazolam at the first injection visit and a single intravenous infusion placebo at the second injection visit.
Dexmedetomidine first injection; Saline second injection	Saline	Subjects in this arm will receive a single intravenous infusion of dexmedetomidine at the first injection visit and a single intravenous infusion placebo at the second injection visit.
Saline first injection; ketamine second injection	Ketamine	Subjects in this arm will receive a single intravenous infusion of placebo at the first injection visit and a single intravenous infusion ketamine at the second injection visit.
Saline first injection; dexmedetomidine second injection	Dexmedetomidine	Subjects in this arm will receive a single intravenous infusion of placebo at the first injection visit and a single intravenous infusion dexmedetomidine at the second injection visit.
Ketamine first injection; Saline second injection	Ketamine	Subjects in this arm will receive a single intravenous infusion of ketamine at the first injection visit and a single intravenous infusion placebo at the second injection visit.
Ketamine first injection; midazolam second injection	Ketamine	Subjects in this arm will receive a single intravenous infusion of ketamine at the first injection visit and a single intravenous infusion midazolam at the second injection visit.
Ketamine first injection; midazolam second injection	Midazolam	Subjects in this arm will receive a single intravenous infusion of ketamine at the first injection visit and a single intravenous infusion midazolam at the second injection visit.
Ketamine first injection; dexmedetomidine second injection	Ketamine	Subjects in this arm will receive a single intravenous infusion of ketamine at the first injection visit and a single intravenous infusion dexmedetomidine at the second injection visit.
Ketamine first injection; dexmedetomidine second injection	Dexmedetomidine	Subjects in this arm will receive a single intravenous infusion of ketamine at the first injection visit and a single intravenous infusion dexmedetomidine at the second injection visit.
Midazolam first injection; Saline second injection	Midazolam	Subjects in this arm will receive a single intravenous infusion of midazolam at the first injection visit and a single intravenous infusion placebo at the second injection visit.
Midazolam first injection; ketamine second injection	Midazolam	Subjects in this arm will receive a single intravenous infusion of midazolam at the first injection visit and a single intravenous infusion ketamine at the second injection visit.
Midazolam first injection; ketamine second injection	Ketamine	Subjects in this arm will receive a single intravenous infusion of midazolam at the first injection visit and a single intravenous infusion ketamine at the second injection visit.
Midazolam first injection; dexmedetomidine second injection	Midazolam	Subjects in this arm will receive a single intravenous infusion of midazolam at the first injection visit and a single intravenous infusion dexmedetomidine at the second injection visit.
Midazolam first injection; dexmedetomidine second injection	Dexmedetomidine	Subjects in this arm will receive a single intravenous infusion of midazolam at the first injection visit and a single intravenous infusion dexmedetomidine at the second injection visit.
Dexmedetomidine first injection; Saline second injection	Dexmedetomidine	Subjects in this arm will receive a single intravenous infusion of dexmedetomidine at the first injection visit and a single intravenous infusion placebo at the second injection visit.
Dexmedetomidine first injection; ketamine second injection	Ketamine	Subjects in this arm will receive a single intravenous infusion of dexmedetomidine at the first injection visit and a single intravenous infusion ketamine at the second injection visit.
Dexmedetomidine first injection; ketamine second injection	Dexmedetomidine	Subjects in this arm will receive a single intravenous infusion of dexmedetomidine at the first injection visit and a single intravenous infusion ketamine at the second injection visit.
Dexmedetomidine first injection; midazolam second injection	Midazolam	Subjects in this arm will receive a single intravenous infusion of dexmedetomidine at the first injection visit and a single intravenous infusion midazolam at the second injection visit.
Dexmedetomidine first injection; midazolam second injection	Dexmedetomidine	Subjects in this arm will receive a single intravenous infusion of dexmedetomidine at the first injection visit and a single intravenous infusion midazolam at the second injection visit.

Primary Outcome Measures

Name	Time	Method
Difference in tobacco withdrawal symptoms	24-hours post infusion	difference in self-reported withdrawal symptoms after infusions
Difference in craving between drug and placebo	24-hours post infusion	difference in self-reported craving for cigarettes after infusions
Number of cigarettes smoked ad lib	24-hours post infusion
Difference in cigarette demand	24-hours post infusion	difference in self-reported cigarette demand after infusions

Trial Locations

Locations (1)

Wake Forest University Health Sciences; 🇺🇸 Winston-Salem, North Carolina, United States