Ultrasound Therapy Effects to Modulate the Inflammatory Reflex

NCT05457907 | Completed FDA Device

• 1 other identifier: IRB-65481
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief 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. This pilot dose-finding study will be the basis for a larger Phase 2 trial in Rheumatoid Arthritis (RA) patients.

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• Change in inflammatory response measured by TNF-α

  Measure the change before and after ultrasound by immunoassay of blood plasma after challenge with LPS.

  baseline to 2 hour post therapy

Secondary Outcomes (3)

• Change in inflammatory response measured by Tumor Necrosis Factor α (TNF-α)

  baseline to 24 hour post therapy

• Change in inflammatory response measured by Interleukin 1 (IL-1)

  baseline to 2 hour post therapy

• Change in inflammatory response measured by Interleukin 6 (IL-6)

  baseline to 2 hour post therapy

Study Arms (2)

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.

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.

Device: Ultrasound device

Interventions

Ultrasound device DEVICE

Low energy ultrasound therapy will be administered to the spleen

Anatomical targeting; Parameter testing

Eligibility Criteria

• Age: 22 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University

Stanford, California, 94305, United States

Location

Related Publications (4)

• 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.

  PMID: 27382171 BACKGROUND

• Tracey KJ. Physiology and immunology of the cholinergic antiinflammatory pathway. J Clin Invest. 2007 Feb;117(2):289-96. doi: 10.1172/JCI30555.

  PMID: 17273548 BACKGROUND

• Cotero 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.

  PMID: 30862827 BACKGROUND

• Zachs 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.

  PMID: 30862842 BACKGROUND

MeSH Terms

Interventions

Ultrasonography

Intervention Hierarchy (Ancestors)

Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis

Study Officials

• Robert M Fairchild, MD, PhD

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: DEVICE FEASIBILITY
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: ASSISTANT PROFESSOR OF MEDICINE - IMMUNOLOGY & RHEUMATOLOGY

Study Record Dates

• First Submitted: July 8, 2022
• First Posted: July 14, 2022
• Study Start: January 1, 2023
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: September 23, 2024

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)