Healthy ParticipantsVALIRAT1NCT07393815
"Physiological Responses to Manual Pressure in Healthy Adults"
A study testing "Manual Pressure Protocol", Manual Therapy Protocols (DLM, light and moderate-pressure massage) and Graded Sustained Pressure in people with Healthy Participants, run by Universidad Europea de Madrid at 1 site in Spain.
Trial summary
This randomized experimental study will investigate how different intensities and application patterns of manual pressure applied to the upper trapezius muscle affect physiological responses in healthy adults. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Participants
- What is being tested?
- "Manual Pressure Protocol", Manual Therapy Protocols (DLM, light and moderate-pressure massage) and Graded Sustained Pressure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteSpain
- Study dates
- Mar 2026to Jul 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age 18-65 years.
- Healthy volunteers without diagnosed cardiovascular, neurological or severe musculoskeletal disorders.
- No significant pain or pathology in the cervical, shoulder or upper back region that would interfere with pressure application.
- Ability to understand the study procedures and to provide written informed consent.
- Availability to attend the experimental session and the DEXA visit.
Who cannot join
- History of major cardiovascular disease (e.g., ischemic heart disease, heart failure, clinically significant arrhythmias, uncontrolled hypertension, stroke or transient ischemic attack).
- Neurological disorders affecting pain perception or autonomic function.
- Acute or chronic musculoskeletal conditions in the cervical or shoulder region that contraindicate manual pressure on the upper trapezius.
- Coagulation disorders or high-dose anticoagulant/antiplatelet therapy that increases bleeding risk.
- Dermatologic conditions or skin lesions at sensor placement or pressure application sites.
- Pregnancy or suspected pregnancy (due to DEXA scan).
Show all 9Show fewer
- Regular use of medications with a major impact on autonomic or cardiovascular responses (e.g., beta-blockers, antiarrhythmics) that cannot be paused according to medical judgement.
- Substance abuse or acute alcohol/drug intake in the 24 hours prior to the experimental session.
- Any other condition that, in the opinion of the investigators, may compromise safety or compliance.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Spain1 site
Universidad Europea de Madrid
Villaviciosa de Odón
Elena Velarde Dr, (34) 0912115268, elena.velarde@universidadeuropea.es
Raquel Pérez García
About this study
Official title: Physiological Responses to Graded Manual Pressure in Healthy Adults: a Randomized Experimental Study on Autonomic, Hormonal, Sensory and Vascular Outcomes
This randomized experimental study will investigate how different intensities and application patterns of manual pressure applied to the upper trapezius muscle affect physiological responses in healthy adults. Participants will be randomly assigned to one of three groups: (A) graded sustained pressure at a single point over the upper trapezius, (B) graded longitudinal kneading over a defined area of the upper trapezius, or (C) three standardized manual therapy protocols with increasing pressure (manual lymphatic drainage, light-pressure massage and moderate-pressure massage).
In groups A and B, five individualized pressure levels (0, 25, 50, 75 and 95% of each participant's pressure pain threshold) will be delivered for 2 minutes each in a single session. In group C, each participant will receive the three manual therapy protocols in separate randomized sessions. Autonomic (heart rate and heart rate variability), hormonal (capillary cortisol and VEGF in group C), sensory (mechanical pain thresholds), hemodynamic (blood pressure) and, in group C, vascular (left common carotid artery ultrasound) responses will be recorded before and after the interventions. The study will provide dose-response and mechanistic information to inform safer and more individualized manual therapy protocols.
Read the detailed description
This prospective randomized experimental study will be conducted in healthy adults to characterize acute physiological responses to different intensities and patterns of manual pressure applied to the upper trapezius muscle. Participants will be randomly allocated to one of three experimental groups:
- Group A - Graded sustained pressure: a personalized pressure scale is defined based on the individual pressure pain threshold (PPT) measured with an algometer. Five pressure levels are set at 0% (contact without pressure), 25%, 50%, 75% and 95% of PPT, and applied as sustained pressure at a single point over the upper trapezius.
- Group B - Graded longitudinal kneading: the same personalized pressure scale (0, 25, 50, 75 and 95% of PPT) is applied as longitudinal kneading distributed over a predefined area of the upper trapezius.
- Group C - Manual therapy protocols: each participant receives three standardized manual therapy protocols in separate sessions, with randomized order: manual lymphatic drainage (approx. 40 minutes at ~40 mmHg), light-pressure massage (0.5-0.8 N/cm², 20-30 minutes) and moderate-pressure massage (2-3 N/cm², 20 minutes), all targeting the upper trapezius and related regions.
In groups A and B, the five pressure levels are each applied for 2 minutes in a single experimental session, in randomized order, with rest periods of at least 5 minutes between levels (extended if needed until heart rate returns within ±10% of baseline). In group C, each manual therapy protocol is applied in a separate session with at least one day between sessions. In all groups, heart rate and heart rate variability are recorded continuously with a chest strap, and skin temperature and skin conductance are continuously monitored with surface sensors. Blood pressure, mechanical pain thresholds (von Frey filaments at predefined trapezius and forearm sites), and capillary blood samples for cortisol are obtained at baseline and immediately after each pressure level or massage protocol. In group C, VEGF is also measured in capillary blood.
In group C only, duplex ultrasound of the left common carotid artery is performed under standardized conditions (semi-recumbent position, head rotated 45° to the right) before the manual therapy protocol and 10 minutes after its completion, to assess luminal diameter, intima-media thickness and peak systolic velocity. All pressure applications in all groups are monitored with a pressure-sensing system (Loadpad) placed on the therapist's hand.
A separate visit includes whole-body dual-energy X-ray absorptiometry (DEXA) to characterize body composition (total and segmental lean mass and fat mass). The main outcome is a heart rate variability index (e.g., RMSSD), while hormonal (cortisol, VEGF in group C), sensory (pain thresholds), hemodynamic (blood pressure) and vascular (carotid ultrasound in group C) measures are considered secondary outcomes. The study is powered assuming a large effect size on HRV based on previous massage research, with a planned sample size of 30 participants per group (N = 90).
- Conditions
- Healthy Participants
- Being tested
- "Manual Pressure Protocol", Manual Therapy Protocols (DLM, light and moderate-pressure massage), Graded Sustained Pressure
- Keywords
- Autonomic Nervous System, Manual Therapy, Pain
- Medical subject headings
- Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
"Manual Pressure Protocol"Other
Manual pressure is applied over the upper trapezius muscle using five individualized pressure levels (0, 25, 50, 75 and 90% of the pressure pain threshold). Each level is applied for 2 minutes in a single experimental session, with randomized order and rest periods between applications. In the Sustained Pressure arm, pressure is maintained at a single point. In the Longitudinal Kneading arm, the same pressure levels are distributed along a predefined area using a kneading technique.
Manual Therapy Protocols (DLM, light and moderate-pressure massage)Other
Three standardized manual therapy protocols targeting the upper trapezius and related regions are applied in separate sessions with at least one day between them and randomized order: (1) manual lymphatic drainage (approx. 40 minutes at ~40 mmHg), (2) light-pressure massage (0.5-0.8 N/cm², 20-30 minutes) and (3) moderate-pressure massage (2-3 N/cm², 20 minutes). Pressure is monitored continuously with a hand-worn pressure sensor.
Graded Sustained PressureOther
Manual pressure applied over the upper trapezius using five individualized pressure levels (0, 25, 50, 75 and 95% of the pressure pain threshold) delivered as sustained pressure at a single point, 2 minutes per level in a single session, with randomized order and rest periods between applications.
| Study group | Role | What they receive |
|---|---|---|
| Experimental: Sustained Pressure | Experimental | Participants receive a graded manual pressure protocol applied as sustained pressure at a single point over the upper trapezius muscle (0, 25, 50, 75 and 90% of individual PPT, 2 minutes each level, randomized order). Receives: Other: Graded Sustained Pressure |
| Experimental: Longitudinal Kneading | Experimental | Participants receive the same graded pressure protocol applied as longitudinal kneading over a defined area of the upper trapezius muscle (0, 25, 50, 75 and 90% of individual PPT, 2 minutes each level, randomized order). Receives: Other: "Manual Pressure Protocol" |
| Experimental: Manual Therapy Protocols | Experimental | Participants receive three standardized manual therapy protocols with increasing pressure in three separate sessions, with randomized order: (1) manual lymphatic drainage (~40 mmHg, approximately 40 minutes), (2) light-pressure massage (0.5-0.8 N/cm², 20-30 minutes) and (3) moderate-pressure massage (2-3 N/cm², 20 minutes), targeting the upper trapezius and related regions. Receives: Other: Manual Therapy Protocols (DLM, light and moderate-pressure massage) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in heart rate variability (HRV) index
Heart rate variability (HRV) will be recorded continuously using a chest strap. An HRV index (e.g., RMSSD or SDNN) will be calculated for predefined periods (baseline, during and after each pressure condition). The primary outcome will be the change in HRV across pressure levels and between intervention groups.
Measured: Baseline and after10 min
Secondary outcomes (10)
Change in capillary cortisol level
Capillary blood cortisol measured by ELISA; changes relative to baseline will be compared across pressure levels and groups.
Measured: Baseline and after10 min
Change in mechanical pain threshold (von Frey)
Mechanical pain thresholds assessed with von Frey filaments at predefined sites (upper trapezius and forearm); changes across pressure levels and groups.
Measured: Baseline and after10 min
Change in blood pressure
Systolic and diastolic blood pressure measured with a manual sphygmomanometer.
Measured: Baseline and after10 min
Change in skin temperature
Continuous recording throughout the session.
Measured: Periprocedural
Change in skin conductance
Skin conductance (electrodermal activity) recorded as an index of sympathetic arousal.
Measured: Periprocedural
Change in common carotid artery diameter
Left common carotid artery luminal diameter (intima-intima) assessed by B-mode ultrasound; absolute and relative changes pre-post session. (Group C only)
Measured: Baseline and after10 min
Change in common carotid artery intima-media thickness (IMT)
Left common carotid artery luminal diameter, intima-media thickness assessed by B-mode and Doppler ultrasound in group C before and 10 minutes after each manual therapy protocol.
Measured: Baseline and after10 min
Change in common carotid artery peak systolic velocity (PSV)
Peak systolic velocity assessed by B-mode and Doppler ultrasound in group C before and 10 minutes after each manual therapy protocol.
Measured: Baseline and after10 min
Body composition (DEXA)
Total and segmental lean mass and fat mass, used as descriptive and potential modulators.
Measured: Baseline
Change in capillary VEGF level
Capillary blood VEGF (vascular endothelial growth factor) measured by ELISA in group C participants at baseline and immediately after each manual therapy protocol; changes relative to baseline will be compared across the three protocols.
Measured: Baseline and after10 min
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2026
- Study startMar 2026 (estimated)
- Primary completionMay 2026 (estimated)
- Study completionJul 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Healthy ParticipantsStudies of the same condition, open and under way.
- 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Universidad Europea de Madrid
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Vanesa Abuín, Universidad Europea de Madrid
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07393815
- Sponsor's protocol ID
- VALIRAT 1
- Acronym
- VALIRAT1
- Status last verified
- Feb 2026
- First submitted
- 19 Dec 2025
- Last updated
- 6 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Unalmis Y, Muniroglu S. Efficacy of fascial manipulation in musculoskeletal pain management: A decade in review (2015-2025). J Bodyw Mov Ther. 2026 Jun;46:147-156. doi: 10.1016/j.jbmt.2025.11.011. Epub 2025 Nov 8.
PubMed 41927169Roura S, Alvarez G, Sola I, Cerritelli F. Do manual therapies have a specific autonomic effect? An overview of systematic reviews. PLoS One. 2021 Dec 2;16(12):e0260642. doi: 10.1371/journal.pone.0260642. eCollection 2021.
PubMed 34855830Picchiottino M, Leboeuf-Yde C, Gagey O, Hallman DM. The acute effects of joint manipulative techniques on markers of autonomic nervous system activity: a systematic review and meta-analysis of randomized sham-controlled trials. Chiropr Man Therap. 2019 Mar 12;27:17. doi: 10.1186/s12998-019-0235-1. eCollection 2019.
PubMed 30911373Mehrara BJ, Radtke AJ, Randolph GJ, Wachter BT, Greenwel P, Rovira II, Galis ZS, Muratoglu SC. The emerging importance of lymphatics in health and disease: an NIH workshop report. J Clin Invest. 2023 Sep 1;133(17):e171582. doi: 10.1172/JCI171582.
PubMed 37655664Pérez García R, Ruiz Miñarro R, Robledo Do Nascimento Y (2018) Efectos del DLM en la respuesta inmunitaria específica. Congreso Internacional de Fisioterapia 1:1
Minguez-Esteban I, De la Cueva-Reguera M, Abuin-Porras V, Romero-Morales C, Almazan-Polo J, Bravo-Aguilar M. Acute sonographic changes in common carotid artery after NESA neuromodulation intervention in healthy adults: a randomized controlled clinical trial. Front Neurosci. 2025 Apr 28;19:1526236. doi: 10.3389/fnins.2025.1526236. eCollection 2025.
PubMed 40356697Lima CR, Martins DF, Reed WR. Physiological Responses Induced by Manual Therapy in Animal Models: A Scoping Review. Front Neurosci. 2020 May 8;14:430. doi: 10.3389/fnins.2020.00430. eCollection 2020.
PubMed 32457570Liao S, Padera TP. Lymphatic function and immune regulation in health and disease. Lymphat Res Biol. 2013 Sep;11(3):136-43. doi: 10.1089/lrb.2013.0012. Epub 2013 Sep 11. No abstract available.
PubMed 24024577Diego MA, Field T. Moderate pressure massage elicits a parasympathetic nervous system response. Int J Neurosci. 2009;119(5):630-8. doi: 10.1080/00207450802329605.
PubMed 19283590Amoroso Borges BL, Bortolazzo GL, Neto HP. Effects of spinal manipulation and myofascial techniques on heart rate variability: A systematic review. J Bodyw Mov Ther. 2018 Jan;22(1):203-208. doi: 10.1016/j.jbmt.2017.09.025. Epub 2017 Oct 3.
PubMed 29332747Alnefaie HA, Alserahi YS, Kattan MI, Alsaedi SS, Shafei SI, Alotaibi AA, Alfahemy MM, Alqethmi FS, Alkhattabi AH (2025). Physiotherapy in the management of musculoskeletal disorders: a systematic review. The review of diabetic studies 21:102-114.
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Physiological Responses to Graded Manual Pressure in Healthy Adults: a Randomized Experimental Study on Autonomic, Hormonal, Sensory and Vascular Outcomes
- ClinicalTrials.gov ID
- NCT07393815
- Acronym / sponsor ID
- VALIRAT1 / VALIRAT 1
- Conditions
- Healthy Participants
- Keywords
- Autonomic Nervous System, Manual Therapy, Pain
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Universidad Europea de MadridUniversity, hospital or other
- Study start
- Mar 2026 (estimated)
- Primary completion
- May 2026 (estimated)
- Study completion
- Jul 2026 (estimated)
- First posted
- 6 Feb 2026 (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 randomized experimental study will investigate how different intensities and application patterns of manual pressure applied to the upper trapezius muscle affect physiological responses in healthy adults. Participants will be randomly assigned to one of three groups: (A) graded sustained pressure at a single point over the upper trapezius, (B) graded longitudinal kneading over a defined area of the upper trapezius, or (C) three standardized manual therapy protocols with increasing pressure (manual lymphatic drainage, light-pressure massage and moderate-pressure massage).
In groups A and B, five individualized pressure levels (0, 25, 50, 75 and 95% of each participant's pressure pain threshold) will be delivered for 2 minutes each in a single session. In group C, each participant will receive the three manual therapy protocols in separate randomized sessions. Autonomic (heart rate and heart rate variability), hormonal (capillary cortisol and VEGF in group C), sensory (mechanical pain thresholds), hemodynamic (blood pressure) and, in group C, vascular (left common carotid artery ultrasound) responses will be recorded before and after the interventions. The study will provide dose-response and mechanistic information to inform safer and more individualized manual therapy protocols.
Detailed description
This prospective randomized experimental study will be conducted in healthy adults to characterize acute physiological responses to different intensities and patterns of manual pressure applied to the upper trapezius muscle. Participants will be randomly allocated to one of three experimental groups:
- Group A - Graded sustained pressure: a personalized pressure scale is defined based on the individual pressure pain threshold (PPT) measured with an algometer. Five pressure levels are set at 0% (contact without pressure), 25%, 50%, 75% and 95% of PPT, and applied as sustained pressure at a single point over the upper trapezius.
- Group B - Graded longitudinal kneading: the same personalized pressure scale (0, 25, 50, 75 and 95% of PPT) is applied as longitudinal kneading distributed over a predefined area of the upper trapezius.
- Group C - Manual therapy protocols: each participant receives three standardized manual therapy protocols in separate sessions, with randomized order: manual lymphatic drainage (approx. 40 minutes at ~40 mmHg), light-pressure massage (0.5-0.8 N/cm², 20-30 minutes) and moderate-pressure massage (2-3 N/cm², 20 minutes), all targeting the upper trapezius and related regions.
In groups A and B, the five pressure levels are each applied for 2 minutes in a single experimental session, in randomized order, with rest periods of at least 5 minutes between levels (extended if needed until heart rate returns within ±10% of baseline). In group C, each manual therapy protocol is applied in a separate session with at least one day between sessions. In all groups, heart rate and heart rate variability are recorded continuously with a chest strap, and skin temperature and skin conductance are continuously monitored with surface sensors. Blood pressure, mechanical pain thresholds (von Frey filaments at predefined trapezius and forearm sites), and capillary blood samples for cortisol are obtained at baseline and immediately after each pressure level or massage protocol. In group C, VEGF is also measured in capillary blood.
In group C only, duplex ultrasound of the left common carotid artery is performed under standardized conditions (semi-recumbent position, head rotated 45° to the right) before the manual therapy protocol and 10 minutes after its completion, to assess luminal diameter, intima-media thickness and peak systolic velocity. All pressure applications in all groups are monitored with a pressure-sensing system (Loadpad) placed on the therapist's hand.
A separate visit includes whole-body dual-energy X-ray absorptiometry (DEXA) to characterize body composition (total and segmental lean mass and fat mass). The main outcome is a heart rate variability index (e.g., RMSSD), while hormonal (cortisol, VEGF in group C), sensory (pain thresholds), hemodynamic (blood pressure) and vascular (carotid ultrasound in group C) measures are considered secondary outcomes. The study is powered assuming a large effect size on HRV based on previous massage research, with a planned sample size of 30 participants per group (N = 90).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Experimental: Sustained Pressure | Experimental | Other: Graded Sustained PressureParticipants receive a graded manual pressure protocol applied as sustained pressure at a single point over the upper trapezius muscle (0, 25, 50, 75 and 90% of individual PPT, 2 minutes each level, randomized order). |
| Experimental: Longitudinal Kneading | Experimental | Other: "Manual Pressure Protocol"Participants receive the same graded pressure protocol applied as longitudinal kneading over a defined area of the upper trapezius muscle (0, 25, 50, 75 and 90% of individual PPT, 2 minutes each level, randomized order). |
| Experimental: Manual Therapy Protocols | Experimental | Other: Manual Therapy Protocols (DLM, light and moderate-pressure massage)Participants receive three standardized manual therapy protocols with increasing pressure in three separate sessions, with randomized order: (1) manual lymphatic drainage (~40 mmHg, approximately 40 minutes), (2) light-pressure massage (0.5-0.8 N/cm², 20-30 minutes) and (3) moderate-pressure massage (2-3 N/cm², 20 minutes), targeting the upper trapezius and related regions. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age 18-65 years.
- Healthy volunteers without diagnosed cardiovascular, neurological or severe musculoskeletal disorders.
- No significant pain or pathology in the cervical, shoulder or upper back region that would interfere with pressure application.
- Ability to understand the study procedures and to provide written informed consent.
- Availability to attend the experimental session and the DEXA visit.
Key exclusion criteria (9 listed)
- History of major cardiovascular disease (e.g., ischemic heart disease, heart failure, clinically significant arrhythmias, uncontrolled hypertension, stroke or transient ischemic attack).
- Neurological disorders affecting pain perception or autonomic function.
- Acute or chronic musculoskeletal conditions in the cervical or shoulder region that contraindicate manual pressure on the upper trapezius.
- Coagulation disorders or high-dose anticoagulant/antiplatelet therapy that increases bleeding risk.
- Dermatologic conditions or skin lesions at sensor placement or pressure application sites.
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 |
|---|---|---|
| "Manual Pressure Protocol"Manual pressure is applied over the upper trapezius muscle using five individualized pressure levels (0, 25, 50, 75 and 90% of the pressure pain threshold). Each level is applied for 2 minutes in a single experimental session, with randomized order and rest periods between applications. In the Sustained Pressure arm, pressure is maintained at a single point. In the Longitudinal Kneading arm, the same pressure levels are distributed along a predefined area using a kneading technique. | Other | Experimental: Longitudinal Kneading |
| Manual Therapy Protocols (DLM, light and moderate-pressure massage)Three standardized manual therapy protocols targeting the upper trapezius and related regions are applied in separate sessions with at least one day between them and randomized order: (1) manual lymphatic drainage (approx. 40 minutes at ~40 mmHg), (2) light-pressure massage (0.5-0.8 N/cm², 20-30 minutes) and (3) moderate-pressure massage (2-3 N/cm², 20 minutes). Pressure is monitored continuously with a hand-worn pressure sensor. | Other | Experimental: Manual Therapy Protocols |
| Graded Sustained PressureManual pressure applied over the upper trapezius using five individualized pressure levels (0, 25, 50, 75 and 95% of the pressure pain threshold) delivered as sustained pressure at a single point, 2 minutes per level in a single session, with randomized order and rest periods between applications. | Other | Experimental: Sustained Pressure |
Primary outcome
Change in heart rate variability (HRV) index
Time frame: Baseline and after10 min
Heart rate variability (HRV) will be recorded continuously using a chest strap. An HRV index (e.g., RMSSD or SDNN) will be calculated for predefined periods (baseline, during and after each pressure condition). The primary outcome will be the change in HRV across pressure levels and between intervention groups.
10 secondary outcomes
Change in capillary cortisol level
Time frame: Baseline and after10 min
Change in mechanical pain threshold (von Frey)
Time frame: Baseline and after10 min
Change in blood pressure
Time frame: Baseline and after10 min
Change in skin temperature
Time frame: Periprocedural
Change in skin conductance
Time frame: Periprocedural
Change in common carotid artery diameter
Time frame: Baseline and after10 min
Change in common carotid artery intima-media thickness (IMT)
Time frame: Baseline and after10 min
Change in common carotid artery peak systolic velocity (PSV)
Time frame: Baseline and after10 min
Body composition (DEXA)
Time frame: Baseline
Change in capillary VEGF level
Time frame: Baseline and after10 min
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2026.
- Background: PubMed 41927169Unalmis Y, Muniroglu S. Efficacy of fascial manipulation in musculoskeletal pain management: A decade in review (2015-2025). J Bodyw Mov Ther. 2026 Jun;46:147-156. doi: 10.1016/j.jbmt.2025.11.011. Epub 2025 Nov 8.
- Background: PubMed 34855830Roura S, Alvarez G, Sola I, Cerritelli F. Do manual therapies have a specific autonomic effect? An overview of systematic reviews. PLoS One. 2021 Dec 2;16(12):e0260642. doi: 10.1371/journal.pone.0260642. eCollection 2021.
- Background: PubMed 30911373Picchiottino M, Leboeuf-Yde C, Gagey O, Hallman DM. The acute effects of joint manipulative techniques on markers of autonomic nervous system activity: a systematic review and meta-analysis of randomized sham-controlled trials. Chiropr Man Therap. 2019 Mar 12;27:17. doi: 10.1186/s12998-019-0235-1. eCollection 2019.
- Background: PubMed 37655664Mehrara BJ, Radtke AJ, Randolph GJ, Wachter BT, Greenwel P, Rovira II, Galis ZS, Muratoglu SC. The emerging importance of lymphatics in health and disease: an NIH workshop report. J Clin Invest. 2023 Sep 1;133(17):e171582. doi: 10.1172/JCI171582.
- BackgroundPérez García R, Ruiz Miñarro R, Robledo Do Nascimento Y (2018) Efectos del DLM en la respuesta inmunitaria específica. Congreso Internacional de Fisioterapia 1:1
- Background: PubMed 40356697Minguez-Esteban I, De la Cueva-Reguera M, Abuin-Porras V, Romero-Morales C, Almazan-Polo J, Bravo-Aguilar M. Acute sonographic changes in common carotid artery after NESA neuromodulation intervention in healthy adults: a randomized controlled clinical trial. Front Neurosci. 2025 Apr 28;19:1526236. doi: 10.3389/fnins.2025.1526236. eCollection 2025.
- Background: PubMed 32457570Lima CR, Martins DF, Reed WR. Physiological Responses Induced by Manual Therapy in Animal Models: A Scoping Review. Front Neurosci. 2020 May 8;14:430. doi: 10.3389/fnins.2020.00430. eCollection 2020.
- Background: PubMed 24024577Liao S, Padera TP. Lymphatic function and immune regulation in health and disease. Lymphat Res Biol. 2013 Sep;11(3):136-43. doi: 10.1089/lrb.2013.0012. Epub 2013 Sep 11. No abstract available.
- Background: PubMed 19283590Diego MA, Field T. Moderate pressure massage elicits a parasympathetic nervous system response. Int J Neurosci. 2009;119(5):630-8. doi: 10.1080/00207450802329605.
- Background: PubMed 29332747Amoroso Borges BL, Bortolazzo GL, Neto HP. Effects of spinal manipulation and myofascial techniques on heart rate variability: A systematic review. J Bodyw Mov Ther. 2018 Jan;22(1):203-208. doi: 10.1016/j.jbmt.2017.09.025. Epub 2017 Oct 3.
- BackgroundAlnefaie HA, Alserahi YS, Kattan MI, Alsaedi SS, Shafei SI, Alotaibi AA, Alfahemy MM, Alqethmi FS, Alkhattabi AH (2025). Physiotherapy in the management of musculoskeletal disorders: a systematic review. The review of diabetic studies 21:102-114.
- Individual participant dataSharing planned: Undecided
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing "Manual Pressure Protocol", Manual Therapy Protocols (DLM, light and moderate-pressure massage) and Graded Sustained Pressure in people with Healthy Participants, run by Universidad Europea de Madrid at 1 site in Spain.
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 5 inclusion and 9 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: opening soon, as of the sponsor's last update on 6 Feb 2026. 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 Spain. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Elena Velarde Dr, Byology Doctor ((34) 0912115268, elena.velarde@universidadeuropea.es), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in heart rate variability (HRV) index (time frame: Baseline and after10 min). 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 NCT07393815, which also lists 11 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 6 Feb 2026.