Back to results

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

Primary Purpose

Tobacco Smoking

Status

Recruiting

Phase

Early Phase 1

Locations

United States

Study Type

Interventional

Intervention

Ketamine

Midazolam

Dexmedetomidine

Saline

About this trial

This is an interventional basic science trial for Tobacco Smoking focused on measuring nicotine addiction, smoking, placebo, sedatives

Eligibility Criteria

21 Years - 55 Years (Adult)All SexesAccepts 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), 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

Sites / Locations

Wake Forest University Health SciencesRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm Type

Experimental

Arm Label

Saline first injection; ketamine second injection

Saline first injection; midazolam second injection

Saline first injection; dexmedetomidine second injection

Ketamine first injection; Saline second injection

Ketamine first injection; midazolam second injection

Ketamine first injection; dexmedetomidine second injection

Midazolam first injection; Saline second injection

Midazolam first injection; ketamine second injection

Midazolam first injection; dexmedetomidine second injection

Dexmedetomidine first injection; Saline second injection

Dexmedetomidine first injection; ketamine second injection

Dexmedetomidine first injection; midazolam second injection

Arm 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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

Difference in craving between drug and placebo

difference in self-reported craving for cigarettes after infusions

Difference in tobacco withdrawal symptoms

difference in self-reported withdrawal symptoms after infusions

Difference in cigarette demand

difference in self-reported cigarette demand after infusions

Number of cigarettes smoked ad lib

Secondary Outcome Measures

Full Information

NCT ID

NCT05505630

First Posted

August 15, 2022

Last Updated

October 16, 2023

Sponsor

Wake Forest University Health Sciences

1. Study Identification

Unique Protocol Identification Number

NCT05505630

Brief Title

The Effects of Sedatives on Tobacco Use Disorder Version 2

Acronym

SED-TUD2

Official Title

The Effects of Sedatives on Tobacco Use Disorder Version 2

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Recruiting

Study Start Date

January 31, 2023 (Actual)

Primary Completion Date

December 2024 (Anticipated)

Study Completion Date

December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Wake Forest University Health Sciences

4. Oversight

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

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Tobacco Smoking

Keywords

nicotine addiction, smoking, placebo, sedatives

7. Study Design

Primary Purpose

Basic Science

Study Phase

Early Phase 1

Interventional Study Model

Crossover Assignment

Masking

ParticipantCare Provider

Allocation

Randomized

Enrollment

52 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Saline first injection; ketamine second injection

Arm Type

Experimental

Arm 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.

Arm Title

Saline first injection; midazolam second injection

Arm Type

Experimental

Arm 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

Arm Title

Saline first injection; dexmedetomidine second injection

Arm Type

Experimental

Arm 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.

Arm Title

Ketamine first injection; Saline second injection

Arm Type

Experimental

Arm 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.

Arm Title

Ketamine first injection; midazolam second injection

Arm Type

Experimental

Arm 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.

Arm Title

Ketamine first injection; dexmedetomidine second injection

Arm Type

Experimental

Arm 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.

Arm Title

Midazolam first injection; Saline second injection

Arm Type

Experimental

Arm 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.

Arm Title

Midazolam first injection; ketamine second injection

Arm Type

Experimental

Arm 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.

Arm Title

Midazolam first injection; dexmedetomidine second injection

Arm Type

Experimental

Arm 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.

Arm Title

Dexmedetomidine first injection; Saline second injection

Arm Type

Experimental

Arm 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.

Arm Title

Dexmedetomidine first injection; ketamine second injection

Arm Type

Experimental

Arm 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.

Arm Title

Dexmedetomidine first injection; midazolam second injection

Arm Type

Experimental

Arm 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.

Intervention Type

Drug

Intervention Name(s)

Ketamine

Other Intervention Name(s)

a dissociative anesthetic used medically for induction and maintenance of anesthesia

Intervention Description

A single dose of IV ketamine will be administered.

Intervention Type

Drug

Intervention Name(s)

Midazolam

Other Intervention Name(s)

benzodiazepine medication

Intervention Description

A single dose of IV midazolam will be administered

Intervention Type

Drug

Intervention Name(s)

Dexmedetomidine

Other Intervention Name(s)

benzodiazepine medication

Intervention Description

A single dose of IV dexmedetomidine will be administered

Intervention Type

Drug

Intervention Name(s)

Saline

Intervention Description

A single dose of IV saline will be administered

Primary Outcome Measure Information:

Title

Difference in craving between drug and placebo

Description

difference in self-reported craving for cigarettes after infusions

Time Frame

24-hours post infusion

Title

Difference in tobacco withdrawal symptoms

Description

difference in self-reported withdrawal symptoms after infusions

Time Frame

24-hours post infusion

Title

Difference in cigarette demand

Description

difference in self-reported cigarette demand after infusions

Time Frame

24-hours post infusion

Title

Number of cigarettes smoked ad lib

Time Frame

24-hours post infusion

10. Eligibility

Sex

All

Minimum Age & Unit of Time

21 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Merideth Addicott

Phone

336-716-7792

maddicot@wakeforest.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Merideth A Addicott, MD

Organizational Affiliation

Wake Forest University Health Sciences

Official's Role

Principal Investigator

Facility Information:

Facility Name

Wake Forest University Health Sciences

City

Winston-Salem

State/Province

North Carolina

ZIP/Postal Code

27157

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Darcy Lockhart

Phone

336-716-6182

alaverdi@wakehealth.edu

First Name & Middle Initial & Last Name & Degree

Merideth A Addicott, MD

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

The Effects of Sedatives on Tobacco Use Disorder Version 2

We'll reach out to this number within 24 hrs