Normal PhysiologyEarly Phase 1NCT07099092
Causal Mechanisms of Odor-Guided Behavior in Humans
A Early Phase 1 study testing TUS PirC and TUS Amy in people with Normal Physiology, run by National Institute on Drug Abuse (NIDA) at 1 site in United States.
Trial summary
Background: Little is known about how different regions of the brain responsible for the human sense of smell guide behaviors. In this study, researchers use a technique called transcranial ultrasound stimulation (TUS) to learn how odors affect the brain and behavior. Read more about this study
- Who is it for?
- Ages 18 to 45 years
- Conditions the study is for
- Normal Physiology
- What is being tested?
- TUS PirC and TUS Amy
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Oct 2026to 14 Jul 2035
- Phase
- Early Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- In order to be eligible to participate in this study, an individual must meet the following criteria:
- Aged 18-45 years old. Justification: Many neural processes change with age, and these changes could introduce unwanted variability in the measured signals.
- In good general health based on the assessment of the Medical Advisory Investigator (MAI) or delegate.
- Right-handed.
Who cannot join
- Individuals who meet any of the following criteria will be excluded from participation:
- Any neurological disorder that would increase seizure risk from TUS such as stroke, brain lesions, previous neurosurgery, epilepsy, any history of seizure or fainting episode of unknown cause, frequent severe headache, or head trauma resulting in loss of consciousness, lasting over 30 minutes or with sequela lasting longer than one month. The MAI will also retain discretion to exclude based on a history of a neurological illness or trauma that may compromise safety or data integrity.
- Predisposition to seizures (e.g., first-degree family history of potentially hereditary epilepsy, etc.).
- Current use (any use in the past week, daily use for more than one week within past 3 months) of any investigational drug or of any medications with psychotropic (e.g., benzodiazepines, etc.), or anti or pro-convulsive action. This will be determined at the discretion of the MAI.
- Unable to undergo MRI, or TUS due to certain metallic or magnetic devices or implants in the body, claustrophobia, or other reasons including numbness or paresthesia of the head.
- History of noise-induced hearing loss or tinnitus.
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- Recent history (within past 12 months) of learning disability, major DSM-5 psychiatric disorder including major affective disorder, ADHD, obsessivecompulsive disorder, schizophrenia, or PTSD. This will be determined at the discretion of the MAI.
- Pattern of alcohol and drug use in the past 12 months that is indicative of harmful use, loss of control over use, or physical dependence.
- Daily nicotine, alcohol, or drug use (excluding caffeine) for at least 4 continuous weeks within the past 12 months.
- Participation in any neuromodulation (e.g., TMS, TUS, tDCS, tACS, etc.) session (excluding the current protocol) in the past two weeks.
- History of anaphylaxis and/or severe food and non-food allergies (e.g., latex, detergents, soap, etc.).
- History of significant chronic obstructive pulmonary disease (COPD) or severe, uncontrolled asthma, as increased levels of carbon dioxide may increase the susceptibility to cavitation and related tissue damage.
- Uncorrected impairments in visual acuity severe enough to affect task participation.
- Non-English speaking. Justification: Data integrity of some of the behavioral tasks used in this study would be compromised as they have only been validated in English. Most importantly, ongoing communication regarding safety procedures is necessary when participants are undergoing TUS and MRI procedures. The inability to effectively communicate TUS and MRI safety procedures in a language other than English could compromise the safety of non-English speaking participants.
- Serious skin disease involving the hands or head, or history of serious systemic allergy involving the skin or mucous membranes such as Stevens-Johnson syndrome, or known history of contact dermatitis to ultrasound gel. Justification: Gel will be applied to the skin on both head and hands, for transducer coupling and electrode placement, respectively. Allergic or adverse reactions to such treatment need to be ruled out.
- Hyposmia, i.e., decreased sense of smell, or anosmia, i.e., loss of smell (Sniffin' Sticks Olfactory Identification Score < 10). Justification: The ability to smell is paramount to task performance.
- Pregnancy. Justification: It is unknown whether MRI and/or TUS pose risks to fetuses.
- Any other condition that in the judgment of the investigators is incompatible with participation.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
National Institute on Drug Abuse
Baltimore, Maryland, 21224
Thorsten Kahnt, 667-312-5175, thorsten.kahnt@nih.gov
About this study
Background:
Little is known about how different regions of the brain responsible for the human sense of smell guide behaviors. In this study, researchers use a technique called transcranial ultrasound stimulation (TUS) to learn how odors affect the brain and behavior.
Read more
Objective:
To learn more about how the human sense of smell works.
Eligibility:
Healthy people aged 18 to 45 years who are right-handed.
Design:
Participants can volunteer for up to 2 different experiments. Each experiment requires 5 visits, each about 1 week apart. Food, alcohol, and caffeine may be limited before visits.
At the start of each visit, participants will answer questions about their health and how well they slept. Their sense of smell will be assessed.
Some visits may include tasks on a computer: While doing these tasks, participants may be asked to smell different odors, look at pictures, and listen to sounds. They will wear devices to track breathing, blood pressure, pulse, and other body responses to the tasks.
Some visits may include TUS: TUS uses ultrasound waves to briefly change brain activity. A gel will be applied to the scalp and hair, and a device will be placed against the participant s head. Participants may feel a tapping, pulling, and/or warm sensation on the skin underneath the device. They may also feel a twitch in their face, neck, arm, or leg muscles. Participants will do tasks before and after TUS.
Some visits will include functional magnetic resonance imaging (fMRI) scans. fMRI uses magnet and radio waves to capture images of the activity inside the brain. Participants will lie on a table that slides into a tube. They will perform tasks inside the scanner.
Read the detailed description
Study Description:
Primary olfactory cortex has been implicated in a variety of odorguided behaviors in both animal models and humans. However, direct causal evidence for the functional role of different primary olfactory regions in humans is currently missing, due to the lack of non-invasive neuromodulation methods that can effectively target deep brain regions. With the recent advancement of transcranial focused ultrasound stimulation (TUS), this challenge can now be overcome. The goal of this protocol is to use TUS to temporarily modulate activity in primary olfactory cortex and thereby assess its contribution to olfactory function.
Objectives:
The primary objective is to determine the causal contribution of primary olfactory brain regions to olfactory functions. The secondary objective is to 1) evaluate the neural mechanisms by which these brain regions support these olfactory functions, and 2) assess the safety profile of TUS.
Endpoints:
The primary endpoint is to determine if TUS of olfactory cortices alters olfactory function. The secondary endpoints are to 1) evaluate whether TUS changes neural activity in olfactory regions and 2) assess the degree to which TUS elicits unwanted side effects in healthy adult participants.
- Conditions
- Normal Physiology
- Being tested
- TUS PirC, TUS Amy, TUS Sham
- Keywords
- Behavioral Tasks, Decision Making, fMRI, TUS
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TUS PirCDevice
120 seconds of 100 Hz low-intensity transcranial ultrasound stimulation targeting piriform cortex
TUS AmyDevice
120 seconds of 100 Hz low-intensity transcranial ultrasound stimulation targeting amygdala
TUS ShamDevice
120 seconds of 100 Hz low-intensity transcranial ultrasound stimulation targeting white matter
| Study group | Role | What they receive |
|---|---|---|
| Experiment 1 | Experimental | TUS targeting PirC or sham TUS before olfactory perceptual decision making task Receives: Device: TUS PirC; Device: TUS Sham |
| Experiment 2 | Experimental | TUS targeting amygdala or sham TUS before olfactory conditioning task Receives: Device: TUS Amy; Device: TUS Sham |
What is being measured
The primary outcome is the main question the study is designed to answer.
Task Performance<TAB>
Responses on behavioral tasks
Measured: Immediately after TUS
Secondary outcomes (2)
task-based fMRI
fMRI responses during behavioral task in Experiment 1
Measured: Immediately after TUS
Report of symptoms
Report of symptoms
Measured: before, during and after TUS
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2025
- Study start28 Oct 2026 (estimated)
- Primary completion14 Jul 2035 (estimated)
- Study completion14 Jul 2035 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Normal PhysiologyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Institute on Drug Abuse (NIDA)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Thorsten Kahnt, Ph.D., Principal investigator, National Institute on Drug Abuse (NIDA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07099092
- Sponsor's protocol ID
- 10002358
- Other IDs
- 002358-DA
- Status last verified
- 10 Sep 2026
- First submitted
- 31 Jul 2025
- Last updated
- 23 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided