The Effects of Sedatives on Tobacco Use Disorder Version 2 (SED-TUD2)

Wake Forest University (WFU)

Status and phase: Completed; Early Phase 1

Conditions: Tobacco Smoking

Treatments: Drug: Dexmedetomidine; Drug: Midazolam; Drug: Saline; Drug: Ketamine

Study type: Interventional

Funder types: Other

Identifiers

NCT05505630

10595 (Other Identifier)

IRB00081012

Details and patient eligibility

About

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.

Full 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.

Enrollment: 20 patients

Sex: All

Ages: 21 to 55 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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20 participants in 12 patient groups

Saline first injection; ketamine second injection

Experimental group

Description:

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.

Treatment:

Drug: Ketamine

Drug: Saline

Saline first injection; midazolam second injection

Experimental group

Description:

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

Treatment:

Drug: Saline

Drug: Midazolam

Saline first injection; dexmedetomidine second injection

Experimental group

Description:

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.

Treatment:

Drug: Saline

Drug: Dexmedetomidine

Ketamine first injection; Saline second injection

Experimental group

Description:

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.

Treatment:

Drug: Ketamine

Drug: Saline

Ketamine first injection; midazolam second injection

Experimental group

Description:

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.

Treatment:

Drug: Ketamine

Drug: Midazolam

Ketamine first injection; dexmedetomidine second injection

Experimental group

Description:

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.

Treatment:

Drug: Ketamine

Drug: Dexmedetomidine

Midazolam first injection; Saline second injection

Experimental group

Description:

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.

Treatment:

Drug: Saline

Drug: Midazolam

Midazolam first injection; ketamine second injection

Experimental group

Description:

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.

Treatment:

Drug: Ketamine

Drug: Midazolam

Midazolam first injection; dexmedetomidine second injection

Experimental group

Description:

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.

Treatment:

Drug: Midazolam

Drug: Dexmedetomidine

Dexmedetomidine first injection; Saline second injection

Experimental group

Description:

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.

Treatment:

Drug: Saline

Drug: Dexmedetomidine

Dexmedetomidine first injection; ketamine second injection

Experimental group

Description:

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.

Treatment:

Drug: Ketamine

Drug: Dexmedetomidine

Dexmedetomidine first injection; midazolam second injection

Experimental group

Description:

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.

Treatment:

Drug: Midazolam

Drug: Dexmedetomidine