HealthyNCT05457907
Ultrasound Therapy Effects to Modulate the Inflammatory Reflex
A study testing Ultrasound device in people with Healthy, run by Stanford University at 1 site in United States.
Trial summary
This two treatment group study, including sham treatment, attempts to measure how ultrasound frequency, duration, intensity, and duty cycle impact its acute anti-inflammatory effect in healthy volunteers. It also attempts to contribute to the evidence regarding the comfort and safety of using therapeutic ultrasound. Read more about this study
- Who is it for?
- Ages 22 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Ultrasound device
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jan 2023to 31 Dec 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 22 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Individuals between 22 and 65 years of age
- No physical disabilities or conditions/diseases that limit capacity to participate in study procedures or otherwise increases risk of harm
- No significant past medical or surgical histories that would render participants at a greater risk of harm
- Sufficient proficiency with the english language to follow verbal instructions during the ultrasound session and to actively participate in the consent process
- Able to attend all study visits at approximately the same time of day (i.e., 8 - 12 pm)
- Able to comprehend the study goals and procedures, and are able to provide informed consent for participation
Who cannot join
- Individuals participating in another research study that may affect the conduct or results of this study
- Individuals considered substantially overweight or obese via body mass index (≥ 29)
- Individuals having or exhibiting any of the following:
- surgery in the past 90 days
- previous surgery of the spleen or splenectomy, esophagus, lungs, stomach, duodenum, or liver
- recent traumatic injury, including intracerebral hemorrhage and visceral injury
Show all 45Show fewer
- end stage renal disease and/or uremia
- active malignancy
- previous leukemia and/or lymphoma
- human immunodeficiency virus infection or AIDS
- rheumatoid arthritis or other immune-mediated diseases (e.g. inflammatory bowel disease)
- arrhythmias, including but not limited to, atrial fibrillation, atrial flutter, clinically significant bradycardia, ventricular arrhythmias, and A-V block
- implanted pacemaker or cardioverter/defibrillator (AICD)
- a history of stable or unstable angina, myocardial infarction, angioplasty or coronary arterial by-pass grafting surgery
- history of stroke or transient ischemic attack (TIA)
- history of deep venous thrombosis (DVT) and/or pulmonary embolism (PE)
- previous episodes of pancreatitis
- spinal disorders
- chronic pain syndromes
- history of thrombosis or bleeding disorders
- stage III-IV pressure ulcers
- sickle cell anemia or other anemia syndromes
- monocytosis
- thrombocytopenia
- diagnosed with fever of unknown origin (FUO)
- previously or currently implanted vagus nerve stimulator
- previously or currently implanted spinal cord stimulator
- other chronically-implanted electronic medical device
- history of diabetes
- history of hypertension
- history of seizures
- history of cancer
- Individuals who have taken any of the following medications within one week of receiving ultrasound delivery:
- anti-coagulant (Coumadin, Xarelto)
- anti-platelet (aspirin, Plavix)
- anti-inflammatory (aspirin, NSAIDs)
- anti-hypertensive (α-methyldopa)
- epinephrine-related drugs, norepinephrine-related drugs, and drugs that stimulate release of epinephrine and/or norepinephrine (Micronefrin, Asthmanefrin)
- immunosuppressive agents (steroids, newer immunomodulatory drugs)
- alpha and/or beta adrenoceptor blocking agents
- anti-seizure medications
- other medications, supplements, etc. that may interfere with the ultrasound delivery or study results
- Individuals that consumed alcohol within 2 days of the baseline visit
- Individuals currently using or have used tobacco or nicotine products within the past 1 month
- Pregnant women
Trial locations and contacts
1 site in 1 country.
About this study
This two treatment group study, including sham treatment, attempts to measure how ultrasound frequency, duration, intensity, and duty cycle impact its acute anti-inflammatory effect in healthy volunteers. It also attempts to contribute to the evidence regarding the comfort and safety of using therapeutic ultrasound. This pilot dose-finding study will be the basis for a larger Phase 2 trial in Rheumatoid Arthritis (RA) patients.
Read the detailed description
Healthy adults aged 22-65 years old without chronic medical conditions will be candidates for the study (see inclusion and exclusion criteria). Each participant during screening will be counseled on the risks and benefits of participating in the study. As discussed in the compensation section, participants will be offered a monetary award for each study session completed. They will be given an electronic consent form and they will have at least 24 hours to review it and can sign at any point they decide to enroll.
Individuals who are interested in participating will have an initial screening blood draw to assess baseline cytokine levels, blood immunogenicity to Lipopolysaccharide (LPS). First half of the participants i.e. 12 participants will be assigned to the treatment group 1, and each participant in this group will receive 4 interventions over a 4 week period with at least 5 days between interventions, but possibly longer depending on their availability. Second half of the participants will be assigned to the treatment group 2, and each participant in this group will receive 3 interventions over a 3 week period with at least 5 days between interventions, but possibly longer depending on their availability.
Participants in both group will be masked to the interventions they are receive. One of the interventions in group 1 will be a 'sham' condition, while the other three interventions will involve active ultrasound administration. Sham intervention will be administered first, and then the remaining three interventions in group 1 will be randomized. Ultrasound parameters for two of the three interventions in group 2 will be chosen and administered based on most effective parameters from group 1. Interventions in group 2 will not be randomized. The two treatment groups, and the interventions within each group are outlined below. Each experimental intervention was chosen to answer a specific translational question regarding the optimal treatment intensity, duty cycle, frequency, and anatomic location. All of the interventions are below the FDA's safety limit for diagnostic ultrasound.
Blood samples will be taken before each treatment, 2 hours post-treatment and 24 hours post-treatment. The blood samples will be challenged within 1 hour of collection with Lipopolysaccharide (LPS) from E coli to induce ex-vivo inflammation. After processing samples will undergo immunoassay testing to assess cytokine, chemokine, and growth factor levels.
- Conditions
- Healthy
- Being tested
- Ultrasound device
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ultrasound deviceDevice
Low energy ultrasound therapy will be administered to the spleen
| Study group | Role | What they receive |
|---|---|---|
| Parameter testing | Experimental | In order to test parameters, each individual will be subjected to four interventions with the ultrasound device, one sham intervention and 3 interventions with varying intensity, frequency, and duty cycle. Receives: Device: Ultrasound device |
| Anatomical targeting | Experimental | In order to test anatomical targeting, each individual will be subjected to four interventions with the ultrasound device, one sham intervention and 2 interventions, varying the anatomical targets. Receives: Device: Ultrasound device |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in inflammatory response measured by TNF-α
Measure the change before and after ultrasound by immunoassay of blood plasma after challenge with LPS.
Measured: baseline to 2 hour post therapy
Secondary outcomes (3)
Change in inflammatory response measured by Tumor Necrosis Factor α (TNF-α)
Measure the change before and after ultrasound by immunoassay of blood plasma after challenge with LPS.
Measured: baseline to 24 hour post therapy
Change in inflammatory response measured by Interleukin 1 (IL-1)
Measure the change before and after ultrasound by immunoassay of blood plasma after challenge with LPS.
Measured: baseline to 2 hour post therapy
Change in inflammatory response measured by Interleukin 6 (IL-6)
Measure the change before and after ultrasound by immunoassay of blood plasma after challenge with LPS.
Measured: baseline to 2 hour post therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jul 2022
- Study start1 Jan 2023
- Primary completion31 Dec 2023
- Study completion31 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- 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
- Phase N/A
- Primary purpose
- Device feasibility
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Robert Fairchild, Stanford University
- Investigators
- Robert M Fairchild, MD, PhD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05457907
- Sponsor's protocol ID
- IRB-65481
- Status last verified
- Dec 2023
- First submitted
- 8 Jul 2022
- Last updated
- 23 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Koopman FA, Chavan SS, Miljko S, Grazio S, Sokolovic S, Schuurman PR, Mehta AD, Levine YA, Faltys M, Zitnik R, Tracey KJ, Tak PP. Vagus nerve stimulation inhibits cytokine production and attenuates disease severity in rheumatoid arthritis. Proc Natl Acad Sci U S A. 2016 Jul 19;113(29):8284-9. doi: 10.1073/pnas.1605635113. Epub 2016 Jul 5.
PubMed 27382171Tracey KJ. Physiology and immunology of the cholinergic antiinflammatory pathway. J Clin Invest. 2007 Feb;117(2):289-96. doi: 10.1172/JCI30555.
PubMed 17273548Cotero V, Fan Y, Tsaava T, Kressel AM, Hancu I, Fitzgerald P, Wallace K, Kaanumalle S, Graf J, Rigby W, Kao TJ, Roberts J, Bhushan C, Joel S, Coleman TR, Zanos S, Tracey KJ, Ashe J, Chavan SS, Puleo C. Noninvasive sub-organ ultrasound stimulation for targeted neuromodulation. Nat Commun. 2019 Mar 12;10(1):952. doi: 10.1038/s41467-019-08750-9.
PubMed 30862827Zachs DP, Offutt SJ, Graham RS, Kim Y, Mueller J, Auger JL, Schuldt NJ, Kaiser CRW, Heiller AP, Dutta R, Guo H, Alford JK, Binstadt BA, Lim HH. Noninvasive ultrasound stimulation of the spleen to treat inflammatory arthritis. Nat Commun. 2019 Mar 12;10(1):951. doi: 10.1038/s41467-019-08721-0.
PubMed 30862842
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ultrasound Therapy Effects to Modulate the Inflammatory Reflex
- ClinicalTrials.gov ID
- NCT05457907
- Acronym / sponsor ID
- IRB-65481
- Conditions
- Healthy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Study start
- 1 Jan 2023 (actual)
- Primary completion
- 31 Dec 2023 (actual)
- Study completion
- 31 Dec 2023 (actual)
- First posted
- 14 Jul 2022 (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.
This two treatment group study, including sham treatment, attempts to measure how ultrasound frequency, duration, intensity, and duty cycle impact its acute anti-inflammatory effect in healthy volunteers. It also attempts to contribute to the evidence regarding the comfort and safety of using therapeutic ultrasound. This pilot dose-finding study will be the basis for a larger Phase 2 trial in Rheumatoid Arthritis (RA) patients.
Detailed description
Healthy adults aged 22-65 years old without chronic medical conditions will be candidates for the study (see inclusion and exclusion criteria). Each participant during screening will be counseled on the risks and benefits of participating in the study. As discussed in the compensation section, participants will be offered a monetary award for each study session completed. They will be given an electronic consent form and they will have at least 24 hours to review it and can sign at any point they decide to enroll.
Individuals who are interested in participating will have an initial screening blood draw to assess baseline cytokine levels, blood immunogenicity to Lipopolysaccharide (LPS). First half of the participants i.e. 12 participants will be assigned to the treatment group 1, and each participant in this group will receive 4 interventions over a 4 week period with at least 5 days between interventions, but possibly longer depending on their availability. Second half of the participants will be assigned to the treatment group 2, and each participant in this group will receive 3 interventions over a 3 week period with at least 5 days between interventions, but possibly longer depending on their availability.
Participants in both group will be masked to the interventions they are receive. One of the interventions in group 1 will be a 'sham' condition, while the other three interventions will involve active ultrasound administration. Sham intervention will be administered first, and then the remaining three interventions in group 1 will be randomized. Ultrasound parameters for two of the three interventions in group 2 will be chosen and administered based on most effective parameters from group 1. Interventions in group 2 will not be randomized. The two treatment groups, and the interventions within each group are outlined below. Each experimental intervention was chosen to answer a specific translational question regarding the optimal treatment intensity, duty cycle, frequency, and anatomic location. All of the interventions are below the FDA's safety limit for diagnostic ultrasound.
Blood samples will be taken before each treatment, 2 hours post-treatment and 24 hours post-treatment. The blood samples will be challenged within 1 hour of collection with Lipopolysaccharide (LPS) from E coli to induce ex-vivo inflammation. After processing samples will undergo immunoassay testing to assess cytokine, chemokine, and growth factor levels.
Study design
- Primary purpose
- Device feasibility
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Parameter testing | Experimental | Device: Ultrasound deviceIn order to test parameters, each individual will be subjected to four interventions with the ultrasound device, one sham intervention and 3 interventions with varying intensity, frequency, and duty cycle. |
| Anatomical targeting | Experimental | Device: Ultrasound deviceIn order to test anatomical targeting, each individual will be subjected to four interventions with the ultrasound device, one sham intervention and 2 interventions, varying the anatomical targets. |
Who may qualify
- Ages
- 22 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Individuals between 22 and 65 years of age
- No physical disabilities or conditions/diseases that limit capacity to participate in study procedures or otherwise increases risk of harm
- No significant past medical or surgical histories that would render participants at a greater risk of harm
- Sufficient proficiency with the english language to follow verbal instructions during the ultrasound session and to actively participate in the consent process
- Able to attend all study visits at approximately the same time of day (i.e., 8 - 12 pm)
Key exclusion criteria (45 listed)
- Individuals participating in another research study that may affect the conduct or results of this study
- Individuals considered substantially overweight or obese via body mass index (≥ 29)
- Individuals having or exhibiting any of the following:
- Individuals who have taken any of the following medications within one week of receiving ultrasound delivery:
- Individuals that consumed alcohol within 2 days of the baseline visit
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 |
|---|---|---|
| Ultrasound deviceLow energy ultrasound therapy will be administered to the spleen | Device | Anatomical targeting, Parameter testing |
Primary outcome
Change in inflammatory response measured by TNF-α
Time frame: baseline to 2 hour post therapy
Measure the change before and after ultrasound by immunoassay of blood plasma after challenge with LPS.
3 secondary outcomes
Change in inflammatory response measured by Tumor Necrosis Factor α (TNF-α)
Time frame: baseline to 24 hour post therapy
Change in inflammatory response measured by Interleukin 1 (IL-1)
Time frame: baseline to 2 hour post therapy
Change in inflammatory response measured by Interleukin 6 (IL-6)
Time frame: baseline to 2 hour post therapy
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2024.
- Background: PubMed 27382171Koopman FA, Chavan SS, Miljko S, Grazio S, Sokolovic S, Schuurman PR, Mehta AD, Levine YA, Faltys M, Zitnik R, Tracey KJ, Tak PP. Vagus nerve stimulation inhibits cytokine production and attenuates disease severity in rheumatoid arthritis. Proc Natl Acad Sci U S A. 2016 Jul 19;113(29):8284-9. doi: 10.1073/pnas.1605635113. Epub 2016 Jul 5.
- Background: PubMed 17273548Tracey KJ. Physiology and immunology of the cholinergic antiinflammatory pathway. J Clin Invest. 2007 Feb;117(2):289-96. doi: 10.1172/JCI30555.
- Background: PubMed 30862827Cotero V, Fan Y, Tsaava T, Kressel AM, Hancu I, Fitzgerald P, Wallace K, Kaanumalle S, Graf J, Rigby W, Kao TJ, Roberts J, Bhushan C, Joel S, Coleman TR, Zanos S, Tracey KJ, Ashe J, Chavan SS, Puleo C. Noninvasive sub-organ ultrasound stimulation for targeted neuromodulation. Nat Commun. 2019 Mar 12;10(1):952. doi: 10.1038/s41467-019-08750-9.
- Background: PubMed 30862842Zachs DP, Offutt SJ, Graham RS, Kim Y, Mueller J, Auger JL, Schuldt NJ, Kaiser CRW, Heiller AP, Dutta R, Guo H, Alford JK, Binstadt BA, Lim HH. Noninvasive ultrasound stimulation of the spleen to treat inflammatory arthritis. Nat Commun. 2019 Mar 12;10(1):951. doi: 10.1038/s41467-019-08721-0.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Robert M Fairchild, MD, PhD principal investigator
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ultrasound device in people with Healthy, run by Stanford University 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 6 inclusion and 45 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: finished, as of the sponsor's last update on 23 Sep 2024. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in inflammatory response measured by TNF-α (time frame: baseline to 2 hour post therapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05457907, which also lists 4 linked publications.
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 23 Sep 2024.