Anti-inflammatory Actions of Osteopathic Manipulative Treatment (OMT_taVNS)

February 6, 2023 updated by: Harald Stauss, Burrell College of Osteopathic Medicine

Anti-inflammatory Actions of OMT - Role of the Cholinergic Anti-inflammatory Pathway and Translocation of Immune Cells From Reticular Organs to the Systemic Circulation

This study evaluates the hypothesis that osteopathic manipulative treatment (OMT) and non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) elicit anti-inflammatory actions through activation of the parasympathetic nervous system. In a cross-over design, research participants will be subjected to various combinations of OMT, taVNS, or sham interventions during four study sessions, that are at least one month apart. During each study session research participants will undergo OMT and/or taVNS for 3 consecutive days. Blood pressure and electrocardiogram (ECG) will be recorded on all three study days to assess parasympathetic nervous system function. On the 3rd study day a blood sample will be taken to assess the effects of OMT and/or taVNS on inflammation.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Biological anti-inflammatory drugs, such as TNF-α antagonists, have revolutionized treatment of chronic inflammatory diseases, such as inflammatory bowel disease, rheumatoid arthritis, psoriasis, or other auto-immune disorders and have largely improved prognosis and quality of life of patients affected by these conditions. However, the high cost of these agents is prohibitive for a large number of patients and some patients are not eligible to such treatments because of co-morbidities that constitute contraindications. Thus, there is a need for cost-effective alternative treatment strategies. Activation of the cholinergic anti-inflammatory pathway, which operates through the parasympathetic nervous system, may constitute an alternative approach to treat chronic inflammatory diseases. This pathway has been demonstrated to shift the function of immune cells in reticular organs, such as the spleen from a pro-inflammatory to an anti-inflammatory state. Subsequently, these "reprogrammed" cells translocate to the systemic circulation and reach the site of inflammation. Clinical studies and the investigators' preliminary data suggest that non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) can augment parasympathetic tone and potentially activate the cholinergic anti-inflammatory pathway. Another way of potentially activating this pathway is through osteopathic manipulative treatment (OMT) because some OMT techniques have been demonstrated to increase parasympathetic activity. However, it is not known if such OMT techniques also activate the cholinergic anti-inflammatory pathway. Furthermore, it is not known if osteopathic lymphatic pump techniques augment these anti-inflammatory responses by facilitating translocation of "reprogrammed" immune cells from reticular organs to the systemic circulation. The investigators' long-term goal is to contribute to the development of cost-effective OMT approaches to treat chronic inflammatory diseases. The central hypothesis is that successive applications of different OMT techniques or the combination of taVNS with specific OMT techniques first activate and then augment the cholinergic anti-inflammatory pathway through stimulating parasympathetic tone and facilitating translocation of immune cells. Parasympathetic nervous system function will be assessed by heart rate variability analysis and other cardiovascular parameters that are under the influence of the parasympathetic nervous system. Immune function will be assessed by measuring plasma concentrations of inflammatory mediators (cytokines) and by in vitro cell culture experiments of immune cells. At the completion of these studies, the investigators anticipate to demonstrate that OMT techniques that activate the parasympathetic nervous system and taVNS elicit anti-inflammatory effects. Second, the investigators also anticipate to demonstrate that subsequently applied osteopathic lymphatic pump techniques augment the anti-inflammatory actions of OMT and taVNS by facilitating translocation of "reprogrammed" immune cells from the spleen to the systemic circulation. These outcomes are expected to have important positive impact, because they will potentially lay a mechanistic foundation for future clinical studies applying such combinations of taVNS and OMT techniques to chronic inflammatory diseases, including inflammatory bowel diseases, rheumatoid arthritis, psoriasis, or other auto-immune disorders.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
36

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New Mexico
      • Las Cruces, New Mexico, United States, 88001
        • Recruiting
        • Burrell College of Osteopathic Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age of 18 year or above.

Exclusion Criteria:

  • Age under 18 years
  • Pregnancy
  • Any findings on the osteopathic screening/evaluation that would hinder the effectiveness - of the occipito-atlantal decompression or splenic lymphatic pump technique
  • Any medication that interferes with the autonomic nervous system function or the immune system (e.g., beta-blockers, steroids, TNF-α inhibitors)
  • Any medical condition that affects the autonomic nervous system or the immune system (e.g., splenomegaly, Epstein-Barr infection within the last 6 months, autonomic neuropathy, pure autonomic failure, rheumatic or autoimmune diseases, acquired autoimmune deficiency syndrome)
  • Any chronic diseases, such as diabetes and hypertension
  • Current drug or alcohol abuse.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: BASIC_SCIENCE
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Osteopathic Manipulative Treatment (OMT)
In 4 randomized study sessions, combinations of two different osteopathic manipulative treatment (OMT) techniques (occipito-atlantal decompression [OA DC] and splenic lymphatic pump technique [SpLPT]) or their respective sham interventions will be performed. The 4 study sessions are at least one month apart and consist of 3 consecutive study days on which the same combination of OMT techniques or sham interventions will be performed.
Procedure: Occipito-Atlantal Decompression (OA DC)
The participant lies supine in a relaxed state while the investigator cradles the patient's head with their hands, middle finger pads along the inferior aspect of inion, reaching to the occipito-atlantal joint. The investigator then applies gentle posterior and cephalad traction to the occiput, while bringing the elbows together. This results in supination of the hands and separation of the middle fingers, creating a posterior-lateral force vector to either side of the foramen magnum. The pressure is maintained until softening of the underlying structures is felt. The procedure is applied for 10 minutes.
Procedure: Sham Occipito-Atlantal Decompression (Sham OA DC)
The participant lies supine in a relaxed state while the investigator applies light touch to the patient's head with their hands.
Procedure: Splenic Lymphatic Pump Technique (SpLPT)
With the participant supine, the investigator places a posterior hand along the left lower ribcage, and a superior hand over the left costal arch, encompassing the spleen. The investigatory compresses and releases the spleen at a rate of 20 compressions/min for 3 min.
Procedure: Sham Splenic Lymphatic Pump Technique (Sham SpLPT)
With the participant supine, the investigator places a posterior hand along the left lower ribcage, and a superior hand over the left costal arch, encompassing the spleen. The investigator will maintain light touch at these positions for 3 minutes. No compressions are performed.
EXPERIMENTAL: Transcutaneous Auricular Vagus Nerve Stimulation (taVNS)
In 4 randomized study sessions, combinations of non-invasive transcutaneous auricular vagus nerve stimulation (taVNS), osteopathic splenic lymphatic pump technique (SpLPT) or their respective sham interventions will be performed. The 4 study sessions are at least one month apart and consist of 3 consecutive study days on which the same combination of taVNS, SpLPT, or sham interventions will be performed.
Procedure: Splenic Lymphatic Pump Technique (SpLPT)
With the participant supine, the investigator places a posterior hand along the left lower ribcage, and a superior hand over the left costal arch, encompassing the spleen. The investigatory compresses and releases the spleen at a rate of 20 compressions/min for 3 min.
Procedure: Sham Splenic Lymphatic Pump Technique (Sham SpLPT)
With the participant supine, the investigator places a posterior hand along the left lower ribcage, and a superior hand over the left costal arch, encompassing the spleen. The investigator will maintain light touch at these positions for 3 minutes. No compressions are performed.
Device: Transcutaneous Auricular Vagus Nerve Stimulation (taVNS)
A bipolar clip electrode is attached to the auricle at the location of the cymba conchae. Electrical stimulation (30 Hz stimulation frequency, 300 μs pulse width) is applied for 10 min. The stimulation current is determined individually for each participant by slowly increasing the stimulation current until the participants feel a mild tingling sensation at the site of the electrode. Then the current is gradually reduced until the tingling sensation disappears. This current will then be used for taVNS. A TENS 7000 or EMS 7500 device (510(k): K080661) is used.
Device: Sham Transcutaneous Auricular Vagus Nerve Stimulation (Sham taVNS)
A bipolar clip electrode is attached to the auricle at the location of the cymba conchae but no electrical current is applied to the electrode.
NO_INTERVENTION: Time Control
In 4 study sessions, no intervention will be performed. As with the two experimental arms, the 4 study sessions are at least one month apart and consist of 3 consecutive study days on which no intervention will be performed. This arm serves as a time control group.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Effect of the Interventions on Inflammation
Time Frame: 2 days
The effect of the interventions on inflammation is assessed by plasma levels of pro- and anti-inflammatory cytokines; activation or inactivation of immune cells in the blood; and release of cytokines from TLR-ligand-activated immune cell cultures. All of these inflammatory measures will be determined from blood samples collected on the third study day and therefore, reflect the cumulative effect of the three study days.
2 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in Autonomic Nervous System Function Induced by the Interventions
Time Frame: 110 minutes
The change in autonomic nervous system function induced by the interventions is assessed by the difference in heart rate variability parameters and baroreceptor-heart rate reflex sensitivity determined before and after the interventions on each study day.
110 minutes
Cumulative Effect of the Interventions on Autonomic Nervous System Function
Time Frame: 2 days
The cumulative effect of the interventions on autonomic nervous system function is assessed by the change in heart rate variability parameters and baroreceptor-heart rate reflex sensitivity from the first to the third study day.
2 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Burrell College of Osteopathic Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 6, 2020

Primary Completion (ANTICIPATED)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2023

Study Completion (ANTICIPATED)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 21, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 25, 2019

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 26, 2019

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 8, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 6, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • BCOM EG 0003_2019

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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