Non-Invasive Deep Brain Neuromodulation for Smoking Cessation

This study will develop novel low intensity focused ultrasound (LIFU) therapy to help people to quit cigarette smoking. Smoking is associated with cancers of the lung. Available smoking cessation methods help many to quit. However, for the many who continue to smoke despite the strong desire to quit and after exhausting existing therapeutic approaches, new treatment methods are needed. Without more effective treatment, many will continue to smoke, and our progress on cancer prevention through smoking cessation may decelerate as these associated cancer risks will remain. Brain imaging research has identified specific areas of the brain linked to severe nicotine addiction, but up to now there are no effective ways to directly target most of these deeper brain regions. LIFU is a new and safe method to modulate brain functions that can either inhibit overactive activity or restore normal activity levels. The purpose of this study is to provide a novel ultrasound-based neuromodulation strategy for smoking cessation in people who have difficulty to quit smoking despite numerous serious attempts in their lives. LIFU works by sending acoustic pressure modulating neural activity in the human brain.

Study Overview

• Status: Not yet recruiting
• Conditions: Nicotine Addiction
• Intervention / Treatment: Device: Low intensity focused ultrasound with active stimulations; Device: low intensity focused ultrasound with sham stimulations

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xiaoming Du, PhD; Phone Number: 443-882-9717; Email: Xiaoming.Du@uth.tmc.edu
• Study Contact Backup: Name: Alina Siatka; Phone Number: 713-486-2740; Email: Alina.Siatka@uth.tmc.edu

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas Health Science Center at Houston
      • Contact: Xiaoming Du, PhD; Phone Number: 443-882-9717; Email: Xiaoming.Du@uth.tmc.edu
      • Contact: Alina Siatka; Phone Number: 713-486-2740; Email: Alina.Siatka@uth.tmc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Must be a smoker for 5 or more years and within 20 to 60 years of age
2. Must not meet exclusion criteria for MRI scanning (e.g., non-fixed magnetizable objects)
3. Must not have ongoing unstable medical, neurological or psychiatric illness as determined by a combination of history, medical record, and/or examination.
4. Must be a current smoker with average of 5 cigarettes or more a day for the last month or longer.
5. Report 3 or more trials of smoking cessation attempts using nicotine replacement, e-cig, TMS, varenicline or other smoking cessation drugs, psychotherapy or other means.

Exclusion Criteria:

1. Failed TMS screening questionnaire.
2. Significant alcohol or other drug use (substance dependence within the recent months) or positive urine toxicology screen for substance not prescribed other than nicotine or marijuana dependence.
3. Cannot refrain from using alcohol and/or marijuana 24 hours or more prior to experiments.
4. Taking > 400 mg clozapine/day and not on anti-seizure medication(s) with sufficient dose.
5. Woman who is pregnant (child-bearing potential but not on contraceptive and missing menstrual period; or by self-report; or by positive pregnancy test) or has had unprotected sexual intercourse without birth control in the last 4 weeks.
6. In ongoing smoking cessation treatment, clinical trial, or nicotine replacements (except for the current study)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active low intensity focused ultrasound (LIFU); Participants in this group will receive active LIFU treatment	Device: Low intensity focused ultrasound with active stimulations; Participants will receive two LIFU sessions a week for 4 weeks.
Sham Comparator: Sham LIFU; Participants in this group will receive sham LIFU treatment	Device: low intensity focused ultrasound with sham stimulations; Participants will receive two LIFU sessions a week for 4 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cigarette per day (CPD)	Cigarette per day (CPD) is measured to index smoking reduction and cessation.	Baseline, session 1 (about 1-2 days after baseline), session 8 (about 4 weeks after baseline), and 1-week follow up (about 5 weeks after baseline).
Brain connectivity as indicated by resting state functional connectivity (rsFC) value as assessed by functional magnetic resonance imaging (fMRI)	The strength of rsFC from fMRI is used to represent the brain activities that are corresponding to the transcranial magnetic stimulation (TMS) effect on smoking reduction/cessation.	session 1 (about 1-2 days after baseline) and session 8 (about 4 weeks after baseline).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
End-expired carbon monoxide (CO)	End-expired CO measure is an instant measure of smoking status, with higher CO level indicating more severe recent smoking behavior.	Baseline, session 1 (about 1-2 days after baseline), session 8 (about 4 weeks after baseline), and 1-week follow up (about 5 weeks after baseline).
Urinary cotinine level	Urinary cotinine is an index of smoking status, with higher cotinine concentrations indicating more severe smoking behavior.	Baseline, session 1 (about 1-2 days after baseline), session 8 (about 4 weeks after baseline), and 1-week follow up (about 5 weeks after baseline).
Quit rate (%)	Quit rate is an index of smoking cessation effects of the treatment.	Session 1 (about 1-2 days after baseline), session 8 (about 4 weeks after baseline), and 1-week follow up (about 5 weeks after baseline).

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center, Houston
• Investigators: Principal Investigator: Xiaoming Du, PhD, The University of Texas Health Science Center, Houston

Study record dates

Study Major Dates

• Study Start (Estimated): March 15, 2026
• Primary Completion (Estimated): November 30, 2030
• Study Completion (Estimated): November 30, 2030

Study Registration Dates

• First Submitted: December 19, 2025
• First Submitted That Met QC Criteria: December 19, 2025
• First Posted (Actual): December 23, 2025

Study Record Updates

• Last Update Posted (Actual): February 11, 2026
• Last Update Submitted That Met QC Criteria: February 10, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: low intensity focused ultrasound
• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Tobacco Use Disorder
• Other Study ID Numbers: HSC-MS-25-1070

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No