Physiological Responses to Osteopathic Manipulative Techniques in Healthy Young Adults
Phase: NA
Conditions: Healthy Young Adults
Sponsor: Touro University Nevada

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ClinicalTrials.gov PRS DRAFT Receipt (Working Version) 
Last Update: 05/25/2022 18:02 
ClinicalTrials.gov ID: [Not yet assigned] 
  
Study Identification 
Unique Protocol ID: TUN IRB4-10-13A 
Brief Title: Physiological Responses to Osteopathic Manipulative Techniques in Healthy 
Young Adults 
Official Title: Physiological Responses to Osteopathic Manipulative Techniques in Healthy 
Young Adults 
Secondary IDs:  
Study Status 
Record Verification: April 2022 
Overall Status: Completed 
Study Start: October 4, 2013 [Actual] 
Primary Completion: August 7, 2019 [Actual] 
Study Completion: August 7, 2019 [Actual] 
Sponsor/Collaborators 
Sponsor: Touro University Nevada 
Responsible Party: Principal Investigator 
Investigator: Marina Ioudina [mioudina] 
Official Title: Assistant Professor 
Affiliation: Touro University Nevada 
 
Collaborators:  
Oversight 
U.S. FDA-regulated Drug: No 
U.S. FDA-regulated Device: No 
U.S. FDA IND/IDE: No 
Human Subjects Review: Board Status: Approved 
Approval Number: IRB4-10-13A, IRB 8-09-17A 
Board Name: Touro University Nevada IRB 
Board Affiliation: Touro University Nevada 
Phone: 702-777-4784 
Email: cvanier@touro.edu 
Address: 
 
Touro University Nevada 
874 American Pacific Drive 
Henderson NV 89014 
 
 

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Data Monitoring: No 
FDA Regulated Intervention: No 
Study Description 
Brief Summary: This study was designed to investigate the effect of selected osteopathic 
manipulative techniques (OMT) on cardiovascular functions in healthy young 
men and women. 
This work addressed questions regarding physiological responses to OMT in 
maintaining the cardiovascular homeostasis by (1) measuring changes in the 
cardiac autonomic nerves activity, (2) measuring changes in cardiovascular 
parameters such as blood pressure, cardiac contractility, and heart rate, and (3) 
investigating if changes in the cardiac autonomic nerves activity were related to 
changes in blood pressure, cardiac contractility, or heart rate. 
This controlled not-randomized pilot study with repeated measures was 
conducted at the Touro University Nevada College of Osteopathic Medicine. 
Healthy 21-35 years old students and employees volunteered in the study. The 
experimental group received the three cranial osteopathic manipulative 
techniques, namely, occipital-atlantal decompression, occipital-mastoid 
decompression, and compression of the fourth ventricle, consecutively applied. 
This study included two control groups; one group received sham 
manipulations, and the second group did not receive any manipulations and 
was the non-touch group. 
The computerized MP150 BIOPAC System was used for data collection and 
analysis. The skin electrodes were used for the one-lead ECG and impedance 
cardiography. Digital data were recorded during the entire experimental 
protocol. The blood pressure was measured manually before and after the 
experimental procedure using blood pressure cuff and stethoscope. 
Cardiovascular responses to OMT were evaluated by using the heart rate 
variability test (HRV), calculating changes in cardiac contractility, and 
comparing changes in pre- and post- blood pressure readings. 
An analysis of variance (ANOVA) with a Bonferroni post-hoc test was used to 
evaluate treatment effects. The type I error rate (alpha) was set at 0.05. 
Detailed Description: Healthy, 21-35 years old, male and female volunteers were recruited from 
Touro University students, faculty and staff using a brochure, poster, e-mail and 
personal conversation. Each participant signed an informed consent form. 
Participants were allowed to participate in multiple experiments (in the 
experimental and control groups) at least 7 days after the last experiment. 
Each subject’s weight and height were measured before the procedure. 
Anthropometric measures were used in cardiac impedance analysis, and as 
descriptive statistics of the studied population. All cardiovascular parameters 
were recorded by using a non-invasive method. We used disposable skin 
electrodes for impedance cardiography and a one-lead ECG. 
The subjects were lying in the supine position and were asked to relax. All 
surface electrodes were connected to the computerized MP150 BIOPAC 
System for data recording. The duration of experimental protocol was about 30 
minutes, and included three intervals: 10 minutes, pre-OMT rest phase (Rest); 8 
to12 minutes (about 10 minutes) of the OMT/Sham (Manipulations); and 10 
minutes post-OMT recovery phase (Recovery). 
OMT and sham manipulations were administered by an osteopathic physician. 
The participant lied supine with physician seated at the side of the table facing 
the participant. Cranial OMT included three techniques and was administered in 
the following sequence: occipital-atlantal decompression, occipital-mastoid joint, 
and compression of the fourth ventricle. Control subjects received the sham 
manipulative procedure or relaxed in supine position (non-touch control). The 
total duration of OMT was controlled by an osteopathic physician and was 

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about 10 minutes. 
Occipital-atlantal decompression: Patient is in the supine position. The operator 
places the tip of a finger against the posterior tubercle of the atlas and holds 
that bone anteriorly, preventing it from moving posteriorly with the condyles as 
the patient nods or tips the head forward. This will release tension between the 
occipital condyles and the first cervical vertebrae. 
Occipital-mastoid joint decompression: The occipital squama is gently moved 
forward and upward (anteriorly and superiorly) with the pads of the long finger, 
and the mastoid process of the temporal bone is lifted anterolaterally with the 
pads of the index fingers. This technique decompresses the jugular foramen, 
which the vagus nerve passes through. 
Compression of the fourth ventricle: Manipulation is accomplished by having the 
operator’s hands cupped to receive the lateral angles and supra-occiput on their 
thenar eminences. Gentle compression medially is maintained (generally 2 to 3 
minutes) until tissue changes, such as a softening or increased motion, are 
noted in the supraoccipital area. 
Sham: The osteopathic physician placed his hands on the skull of the subject 
but did not influence cranial motion. The sham manipulative procedure (SMP) 
was administered for 10 minutes.  
All manipulations were administered by the osteopathic physician; experiments 
were conducted at Touro University Nevada. Data were collected by a non-
invasive method using BIOPAC Systems, Inc. Equipment MP150 for data 
acquisition and analysis. The protocol consisted of three phases: rest before 
manipulations (10 min), manipulations (OMT) (approximately 10 min), and 
recovery after manipulations (10 min). 
Data analysis: Most cardiovascular response variables were measured at 
baseline, immediately after manipulation (“immediate response”), and at the 
end of protocol (“after rest”). The immediate responses and at the end of 
protocol were calculated on a percentage basis relative to baseline to control 
some individual variations. 
The percent response variables were each analyzed in a three-way analysis of 
variance (ANOVA) which included time (“Immediate response”, “after rest”), 
treatment (cranial manipulation, sham), and sex (male, female) as fixed effects. 
For significant interactions in the ANOVA, a Bonferroni post-hoc test was used 
to compare treatment effects within time, sex, or both. The type I error rate 
(alpha) was set at 0.05. The relationships among dependent variables were 
described with Spearman correlations between percent response variables 
within. Analyses were done in Rv3.5.1 (R Core Team 2018). 
 
Conditions 
Conditions: Healthy Young Adults 
 
Keywords: Osteopathic manipulations, 
 autonomic,  
cardiovascular 
 
Study Design 
Study Type: Interventional 
Primary Purpose: Basic Science 
Study Phase: N/A 
Interventional Study Model: Parallel Assignment 

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Number of Arms: 3 
Masking: None (Open Label) 
 
Allocation: Non-Randomized 
Enrollment: 51 [Actual] 
Arms and Interventions 
Arms 
Assigned Interventions 
Experimental: Cranial OMT 
The experimental group received the three cranial 
osteopathic manipulative techniques, occipital-atlantal 
decompression (OAD), occipital-mastoid 
decompression (OMD), and compression of the fourth 
ventricle (CV4), consecutively applied. 
 
Procedure/Surgery: Cranial manipulation group, or cranial 
osteopathic techniques (OMM) 
Cranial OMT procedure: Subjects were relaxed lying on 
the back for entire time of the research protocol 
(approximately 30 min). Osteopathic physician 
performed the osteopathic manipulations using his 
hands. The physician gently applied a small amount of 
force to the neck and head to release tissue tension 
until feeling a softening and warmth of tissues. Subjects 
experienced a sensation of slight pulling, releasing, or 
relaxing of the tissue. 
Other Names: 
•  Cranial osteopathic manipulations, cranial 
osteopathic techniques, cranial OMT procedure 
 
Sham Comparator: Sham manipulation 
The osteopathic physician placed his hands on the skull 
of the subject but did not influence cranial motion. 
 
Procedure/Surgery: Sham manipulation 
The osteopathic physician placed his hands on the skull 
of the subject but did not influence cranial motion. 
Other Names: 
•  Sham 
 
No Intervention: Non touch group 
The control group whose members did not receive any 
manipulations. 
 
 
Outcome Measures 
Primary Outcome Measure: 
1.  Heart rate variability 
The heart rate variability test was used to study the effect of OMT on heart rate and, by inference, on autonomic 
nervous system activity. A decrease in heart rate accompanied by an increase in vagal and decrease in sympathetic 
activity would indicate parasympathetic activation by OMT. 
[Time Frame: The responses were measured immediately after the physician finished OMT/Sham (after Manipulations 
phase) and 10 minutes after post-OMT/Sham recovery phase (“Recovery”, “after rest”).] 
2.  Myocardial contractility 
Changes in impedance cardiography parameters, such as stroke volume (SV) and cardiac output (CO), were used to 
evaluate the effect of OMT on myocardial contractility. An increase in cardiac output (CO) and stroke volume (SV) 
would indicate the stimulatory effect of selected OMT on myocardial contractility. 
[Time Frame: The responses were measured immediately after the physician finished OMT/Sham (after Manipulations 
phase) and 10 minutes after post-OMT/Sham recovery phase (“Recovery”, “after rest”).] 
3.  Blood pressures 
Systolic and diastolic blood pressure were measured by sphygmomanometer. A decrease in systolic blood pressure in 
response to OMT would indicate a decrease in vascular sympathetic tone. 

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[Time Frame: The blood pressure was measured manually before (before pre-OMT rest) and after the experimental 
procedure (after “Recovery” phase”).] 
Eligibility 
Minimum Age: 21 Years 
Maximum Age: 35 Years 
Sex: All 
Gender Based: No 
Accepts Healthy Volunteers: Yes 
Criteria: Inclusion Criteria: 
Young adults 
• 
Exclusion Criteria: Any pre-existing chronic cardiovascular diseases,  
• 
Any pre-existing pulmonary diseases,  
• 
Any pre-existing renal diseases,  
• 
diabetes mellitus,  
• 
endocrine disorders affecting the cardiovascular system,  
• 
pregnancy,  
• 
musculoskeletal conditions that can affect the use of the cranial OMTs, 
or 
• 
 acute illness that necessitates consulting a healthcare provider. 
Contacts/Locations 
Central Contact Person: Marina Ioudina, MD, PhD, MS 
Email: mioudina@touro.edu 
 
Central Contact Backup: Cheryl Vanier, PhD 
Email: cvanier@touro.edu 
 
Study Officials: Marina Ioudina, MD, PhD, MS 
Study Principal Investigator 
Touro University Nevada 
 
Locations:  
IPDSharing 
Plan to Share IPD: Yes 
All IPD that underlie results in a publication 
Supporting Information: 
Study Protocol 
Informed Consent Form (ICF) 
Time Frame: 
Starting 6 months after publication 
Access Criteria: 
By direct contact with study authors 

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URL: 
References 
Citations: Żurowska A, Malak R, Kołcz-Trzęsicka A, Samborski W, Paprocka-Borowicz M. 
Compression of the Fourth Ventricle Using a Craniosacral Osteopathic 
Technique: A Systematic Review of the Clinical Evidence. Evid Based 
Complement Alternat Med. 2017;2017:2974962. doi: 10.1155/2017/2974962. 
Epub 2017 Oct 18. Review. PubMed 29234380 
Cardoso-de-Mello-E-Mello-Ribeiro AP, Rodríguez-Blanco C, Riquelme-Agulló I, 
Heredia-Rizo AM, Ricard F, Oliva-Pascual-Vaca Á. Effects of the Fourth 
Ventricle Compression in the Regulation of the Autonomic Nervous System: A 
Randomized Control Trial. Evid Based Complement Alternat Med. 
2015;2015:148285. doi: 10.1155/2015/148285. Epub 2015 Jun 14. PubMed 
26199632 
Cerritelli F, Carinci F, Pizzolorusso G, Turi P, Renzetti C, Pizzolorusso F, 
Orlando F, Cozzolino V, Barlafante G. Osteopathic manipulation as a 
complementary treatment for the prevention of cardiac complications: 12-
Months follow-up of intima media and blood pressure on a cohort affected by 
hypertension. J Bodyw Mov Ther. 2011 Jan;15(1):68-74. doi: 
10.1016/j.jbmt.2010.03.005. Epub 2010 May 8. PubMed 21147421 
Cutler MJ, Holland BS, Stupski BA, Gamber RG, Smith ML. Cranial 
manipulation can alter sleep latency and sympathetic nerve activity in humans: 
a pilot study. J Altern Complement Med. 2005 Feb;11(1):103-8. PubMed 
15750368 
Jäkel A, von Hauenschild P. Therapeutic effects of cranial osteopathic 
manipulative medicine: a systematic review. J Am Osteopath Assoc. 2011 
Dec;111(12):685-93. Review. PubMed 22182954 
 
Links:  
Available IPD/Information:  
U.S. National Library of Medicine  |  U.S. National Institutes of Health  |  U.S. Department of Health & Human Services