NCT04177264

Brief Summary

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
36

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Jan 2020

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 21, 2019

Completed
5 days until next milestone

First Posted

Study publicly available on registry

November 26, 2019

Completed
1 month until next milestone

Study Start

First participant enrolled

January 6, 2020

Completed
3.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2023

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2023

Completed
Last Updated

February 8, 2023

Status Verified

February 1, 2023

Enrollment Period

3.6 years

First QC Date

November 21, 2019

Last Update Submit

February 6, 2023

Conditions

Keywords

osteopathic manipulative treatmenttranscutaneous auricular vagus nerve stimulationcytokinesimmune cellsparasympathetic nervous systemheart rate variability

Outcome Measures

Primary Outcomes (1)

  • Effect of the Interventions on Inflammation

    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 Outcomes (2)

  • Change in Autonomic Nervous System Function Induced by the Interventions

    110 minutes

  • Cumulative Effect of the Interventions on Autonomic Nervous System Function

    2 days

Study Arms (3)

Osteopathic Manipulative Treatment (OMT)

EXPERIMENTAL

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)Procedure: Sham Occipito-Atlantal Decompression (Sham OA DC)Procedure: Splenic Lymphatic Pump Technique (SpLPT)Procedure: Sham Splenic Lymphatic Pump Technique (Sham SpLPT)

Transcutaneous Auricular Vagus Nerve Stimulation (taVNS)

EXPERIMENTAL

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)Procedure: Sham Splenic Lymphatic Pump Technique (Sham SpLPT)Device: Transcutaneous Auricular Vagus Nerve Stimulation (taVNS)Device: Sham Transcutaneous Auricular Vagus Nerve Stimulation (Sham taVNS)

Time Control

NO INTERVENTION

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.

Interventions

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.

Osteopathic Manipulative Treatment (OMT)

The participant lies supine in a relaxed state while the investigator applies light touch to the patient's head with their hands.

Osteopathic Manipulative Treatment (OMT)

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.

Osteopathic Manipulative Treatment (OMT)Transcutaneous Auricular Vagus Nerve Stimulation (taVNS)

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.

Osteopathic Manipulative Treatment (OMT)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.

Transcutaneous Auricular Vagus Nerve Stimulation (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.

Transcutaneous Auricular Vagus Nerve Stimulation (taVNS)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age of 18 year or above.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Burrell College of Osteopathic Medicine

Las Cruces, New Mexico, 88001, United States

RECRUITING

MeSH Terms

Conditions

Inflammation

Condition Hierarchy (Ancestors)

Pathologic ProcessesPathological Conditions, Signs and Symptoms

Study Officials

  • Harald M Stauss, MD, PhD

    Burrell College of Osteopathic Medicine

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Harald M Stauss, MD, PhD

CONTACT

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Masking Details
There is no masking. The nature of the intervention makes it impossible to prevent the participants from knowing what intervention will be performed on them. The investigators will be performing the interventions and, thus, cannot be masked.
Purpose
BASIC SCIENCE
Intervention Model
CROSSOVER
Model Details: Three groups of research participants will undergo four study sessions each, during which different combinations of osteopathic manipulative treatment or sham procedures (OMT, Group 1), transcutaneous auricular vagus nerve stimulation combines with OMT or sham procedures (taVNS, Group 2), or no intervention (Group 3, time control) will be performed.
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Associate Professor of Pharmacology

Study Record Dates

First Submitted

November 21, 2019

First Posted

November 26, 2019

Study Start

January 6, 2020

Primary Completion

August 1, 2023

Study Completion

August 1, 2023

Last Updated

February 8, 2023

Record last verified: 2023-02

Data Sharing

IPD Sharing
Will not share

Locations