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
- 11 Nov 2026to 14 Jul 2035
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
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.
Show all 18Show fewer
- 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 start11 Nov 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
- 27 Oct 2026
- First submitted
- 31 Jul 2025
- Last updated
- 6 Nov 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Causal Mechanisms of Odor-Guided Behavior in Humans
- ClinicalTrials.gov ID
- NCT07099092
- Acronym / sponsor ID
- 10002358
- Conditions
- Normal Physiology
- Keywords
- Behavioral Tasks, Decision Making, fMRI, TUS
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- National Institute on Drug Abuse (NIDA)US National Institutes of Health
- Study start
- 11 Nov 2026 (estimated)
- Primary completion
- 14 Jul 2035 (estimated)
- Study completion
- 14 Jul 2035 (estimated)
- First posted
- 1 Aug 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experiment 1 | Experimental | Device: TUS PirC, Device: TUS ShamTUS targeting PirC or sham TUS before olfactory perceptual decision making task |
| Experiment 2 | Experimental | Device: TUS Amy, Device: TUS ShamTUS targeting amygdala or sham TUS before olfactory conditioning task |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (18 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TUS PirC120 seconds of 100 Hz low-intensity transcranial ultrasound stimulation targeting piriform cortex | Device | Experiment 1 |
| TUS Amy120 seconds of 100 Hz low-intensity transcranial ultrasound stimulation targeting amygdala | Device | Experiment 2 |
| TUS Sham120 seconds of 100 Hz low-intensity transcranial ultrasound stimulation targeting white matter | Device | Experiment 1, Experiment 2 |
Primary outcome
Task Performance<TAB>
Time frame: Immediately after TUS
Responses on behavioral tasks
2 secondary outcomes
task-based fMRI
Time frame: Immediately after TUS
Report of symptoms
Time frame: before, during and after TUS
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2026.
- Individual participant dataSharing planned: Undecided
Related trials for Normal Physiology
RecruitingEarly Phase 1
Developing Transcranial Neuromodulation Protocols for Learning and Decision-Making
Normal Physiology
Not yet recruitingPhase 2
A Study of Bimagrumab in Participants With HFpEF
Heart Failure, Diastolic, Diastolic Heart Failure
Not yet recruitingPhase 1
A Study to Assess the Pharmacokinetics and Safety of Revumenib in Participants With Advanced Cancer and Hepatic or Renal Impairment
Relapsed/Refractory (R/R) Hematologic Malignancies, Acute Leukemia
RecruitingPhase 1
A Study to Investigate the Pharmacokinetics and Safety of PKN605 in Participants With Moderate and Severe Renal Impairment Compared to Matched Control Subjects With Normal Renal Function
Participants With Moderate and Severe Renal Impairment and Healthy Participants
Not yet recruitingPhase 2
Hyaluronidase Injections for Sclerodactyly in Patients With Scleroderma
Scleroderma, Sclerodactyly
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Thorsten Kahnt, Ph.D. principal investigator
National Institute on Drug Abuse (NIDA)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
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.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 6 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact NIDA IRP Screening Team ((800) 535-8254, researchstudies@nida.nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Task Performance<TAB> (time frame: Immediately after TUS). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2026.