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

Sponsor

Wake Forest University Health Sciences (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05505630

Collaborator

(none)

Enrollment

Arms

47.9

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

Double-blind, placebo-controlled, randomized mechanistic clinical trial to test a single intravenous dose of ketamine or an active control (midazolam) on cigarette smoking behavior, craving, and neural effects.

Condition or Disease	Intervention/Treatment	Phase
Tobacco Smoking	Drug: Ketamine Drug: Midazolam	Early Phase 1

Detailed Description

This double-blind, placebo-controlled, randomized mechanistic clinical trial will test non-treatment seeking smokers with a single intravenous infusion of ketamine (0.71 mg/kg) or an active control (midazolam, 0.025 mg/kg) in counter-balanced order, 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. A blood sample will be collected 3 hours post-infusion and banked for future metabolite analysis. Physical and subjective effects and adverse effects will be closely monitored throughout.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

52 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Double (Participant, Care Provider)

Primary Purpose:

Basic Science

Official Title:

The Effects of Sedatives on Tobacco Use Disorder Version 2

Anticipated Study Start Date :

Jan 3, 2023

Anticipated Primary Completion Date :

Dec 31, 2026

Anticipated Study Completion Date :

Dec 31, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ketamine then midazolam	Drug: Ketamine A single dose of IV ketamine will be administered. Drug: Midazolam A single dose of IV midazolam will be administered
Experimental: Midazolam then ketamine	Drug: Ketamine A single dose of IV ketamine will be administered. Drug: Midazolam A single dose of IV midazolam will be administered

Arm

Intervention/Treatment

Experimental: ketamine then midazolam

Drug: Ketamine

A single dose of IV ketamine will be administered.

Drug: Midazolam

A single dose of IV midazolam will be administered

Experimental: Midazolam then ketamine

Drug: Ketamine

A single dose of IV ketamine will be administered.

Drug: Midazolam

A single dose of IV midazolam will be administered

Outcome Measures

Primary Outcome Measures

Difference in craving between drug and placebo [24-hours post drug and placebo infusion]
difference in self-reported craving for cigarettes between drug and placebo infusions

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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), liver function test (alanine transaminase) >3 times normal, Blood Urea Nitrogen and Creatinine outside normal range; ECG (electrocardiogram) abnormalities including but not limited to: bradycardia (<55 beats per minute); prolonged corrected QT Framingham formula interval (>450 msec); Wolff-Parkinson White syndrome; wide complex tachycardia; 2nd degree, Mobitz type II heart block; 3rd degree heart block; left or right bundle branch block; pre-existing severe gastrointestinal narrowing (pathologic or iatrogenic).

Meet criteria for lifetime psychosis, schizophrenia, or bipolar disorder or current major depressive disorder
Meet DSM-5 criteria for moderate to severe substance use disorder within the past 6 months other than tobacco/nicotine
Use of psychoactive medications or other drugs that would interact with study drug
History of regular use of ketamine or benzodiazepines for nonmedical purposes
Among women, pregnancy or lactation
Body Mass Index > 40 and/or weight > 350 pounds
Vision cannot be corrected to 20/40

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Wake Forest University Health Sciences

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Merideth Addicott, MD, associate professor, Wake Forest University Health Sciences

ClinicalTrials.gov Identifier:

NCT05505630

Other Study ID Numbers:

IRB00081012

First Posted:

Aug 18, 2022

Last Update Posted:

Aug 22, 2022

Last Verified:

Aug 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Yes

Additional relevant MeSH terms:

Tobacco Use Disorder

Midazolam

Ketamine

Study Results

No Results Posted as of Aug 22, 2022