Low Intensity Focused Ultrasound for Tobacco Use Disorder: High Resolution Targeting of the Human Insula

NCT06405074 | Recruiting DMC FDA Device

• 1 other identifier: 1682519
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to to inhibit the dorsal anterior insula (dAI) with low intensity focused ultrasound (LIFU) to determine the causal role for the dAI in smoking cue induced craving in individuals with tobacco use disorder (TUD); smoking cue induced craving is a clinically important behavior which has been associated with the severity of nicotine addiction. The main question\[s\] it aims to answer are:

• the safety and tolerability of dAI LIFU compared to sham stimulation in individuals with TUD
• the effects of LIFU vs sham to left dAI functional magnetic resonance imaging (fMRI) BOLD activity and craving in response to smoking cue exposure. Participants will undergo anatomical MRI, neurological assessment, clinical assessment and patient query to assess the safety and tolerability of LIFU vs sham. Participants will undergo functional magnetic resonance imaging where we will measure the effect of LIFU vs sham on 1) dAI blood-oxygen-level-dependent (BOLD) activation in response to smoking (compared to neutral) cue exposure and 2) cue-induced craving in individuals with TUD. Each participant will receive LIFU and sham stimulation.

Conditions

Tobacco Use Disorder

Keywords

low intensity focused ultrasound; functional magnetic resonance imaging; insula

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events

  number of adverse events

  immediately prior to 1 session LIFU and within 1 hour post LIFU; immediately prior to 1 session sham and with in 1 hour post shamdays

Secondary Outcomes (1)

• Smoking cue-induced craving

  immediately prior to 1 session LIFU and within 1 hour post LIFU; immediately prior to 1 session sham and with in 1 hour post sham

Study Arms (2)

LIFU/Sham

OTHER

double-blind, sham-controlled, crossover study in N=44 individuals with Tobacco Use Disorder

Device: low intensity focused ultrasound (LIFU)

Sham/LIFU

OTHER

double-blind, sham-controlled, crossover study in N=44 individuals with Tobacco Use Disorder

Device: low intensity focused ultrasound (LIFU)

Interventions

low intensity focused ultrasound (LIFU) DEVICE

Low-intensity focused ultrasound (LIFU) provides an energy source with millimeter resolution that can be focused anywhere in the brain safely and effectively for non-invasive and transient neuromodulation. LIFU is an important advance and of great significance for brain-mapping efforts, diagnostics, and therapies in neuroscience and particularly promising for addiction therapy as it provides unprecedented non-surgical access to the brain regardless of depth. Much lower intensities of focused ultrasound (LIFU) are used so that tissue damage does not occur, but neural activity can be modulated. LIFU utilizes acoustic energy at much lower levels to affect tissue by mechanical effects.

LIFU/Sham; Sham/LIFU

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female veterans aged 18-75 years
• Meet the Diagnostic and Statistical Manual, Fifth edition (DSM-5) criteria for current TUD (moderate to severe) as diagnosed by the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition.
• Currently smoking \> 10 cigarettes per day with no period of abstinence \> 3 months in the last year
• Current use of tobacco in last year is limited to cigarettes
• Currently in Contemplation Stage of motivation for behavior change with respect to smoking as assessed by the University of Rhode Island Change Assessment Scale

You may not qualify if:

• Not under current treatment for smoking cessation.
• No history of head injury, seizures, neurologic disorders including cerebrovascular disease, multiple sclerosis, or neurodegenerative diseases or major medical illness
• Current substance use disorder for a psychoactive substance (except nicotine)
• DSM-5 psychiatric disorder requiring current treatment
• Ferromagnetic implants or other contraindications for MRI
• Taking any psychotropic medication such as antidepressants, anxiolytics and antipsychotics.
• any medication other than psychotropic medications that is known to cross the blood brain barrier and achieve brain penetrance such that it will alter BOLD signal or lower seizure threshold, such as antibiotics, antihistamines or muscle relaxants.
• currently pregnant or breast feeding

Sponsors & Collaborators

• Washington D.C. Veterans Affairs Medical Center: lead

Study Sites (1)

Veterans Affairs Medical Center

Washington D.C., District of Columbia, 20422, United States

RECRUITING

MeSH Terms

Conditions

Tobacco Use Disorder

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Study Officials

• Mary R Lee, MD

  Veterans Affairs Medical Center, Washington DC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mary R. Lee, MD

CONTACT

202-745-8000; mary.lee3@va.gov

Evan Lindeman, BS

CONTACT

evan.lindeman@va.gov

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The Sham condition will be conducted using an interface which does not allow ultrasound energy to pass from the transducer to the target. The administration of LIFU/sham will be conducted in a double-blind fashion.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: within subject, randomized, double-blind, sham-controlled trial

Study Record Dates

• First Submitted: November 16, 2023
• First Posted: May 8, 2024
• Study Start: April 1, 2022
• Primary Completion: March 31, 2026
• Study Completion: March 31, 2026
• Last Updated: November 20, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP, ANALYTIC CODE
• Time Frame: data will be available after analysis of primary and secondary outcomes are completed

Locations

US (1)