Carotid Sinus Massage in Trendelenburg Position for Headache Relief (C-SMART)

Effectiveness of Carotid Sinus Massage in Modified Trendelenburg Position for Acute Headache Episodes: A Pilot Study

Headaches significantly impact patients' quality of life, with tension-type headaches and migraines being among the most prevalent types. There is growing evidence suggesting that blood pressure regulation and baroreceptor activity play a role in headache pathophysiology. Carotid sinus massage (CSM), particularly when combined with the modified Trendelenburg position, may modulate autonomic nervous system activity to relieve headache symptoms.

An initial open-label pilot study (n = 17) was completed, and the results were published in a preprint server for health sciences, the Medical Research Archive (medRxiv), demonstrating the feasibility, safety, and promising preliminary efficacy of CSM+T. Based on these findings, a follow-up randomized, sham-controlled, parallel-arm trial will further evaluate the efficacy of the treatment.

Study Overview

• Status: Recruiting
• Conditions: Migraine; Tension-Type Headache
• Intervention / Treatment: Procedure: Arm A - Carotid Sinus Massage + Trendelenburg (CSM+T); Procedure: Arm B - Sham CSM+T

Detailed Description

This protocol includes two study phases:

1. Pilot Phase (Completed): A single-arm, open-label pilot study was conducted in 17 participants to assess the feasibility and safety of CSM+T for the relief of headaches. Results have been published in medRxiv and support continued investigation.
2. Parallel-Arm Phase (Planned): A randomized, sham-controlled, parallel-arm clinical trial will now be implemented to evaluate efficacy. This phase will enroll 18 participants (9 per arm) to detect a clinically meaningful difference in headache relief with 80% power (α = 0.05, two-sided), accounting for potential attrition.

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Heberto J Suarez-Roca, MD, PhD; Phone Number: +1 (919) 6815688; Email: heberto.suarez.roca@duke.edu

Study Locations

• Argentina
  • Buenos Aires
    • Trenque lauquen, Buenos Aires, Argentina, 6400
      • Recruiting
      • Hospital Pedro T.Orellana, Trenque Lauquen
      • Contact: Heberto J Suarez-Roca, MD, PhD; Phone Number: +1 (919) 6815688; Email: heberto.suarez.roca@duke.edu
      • Contact: Pablo D Anaya, MD; Phone Number: +54 (2392) 400954; Email: pdanaya@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

INCLUSION CRITERIA:

• Participants must be at least 16 years of age.

• Must have a diagnosis of one of the following, according to the International Classification of Headache Disorders (ICHD-3):

  • Migraine
  • Tension-type headache
  • Mixed headache
• The headache episode must have started within the past 24 hours.

EXCLUSION CRITERIA:

• Any contraindication to carotid sinus massage, including:

  • Carotid bruits
  • Recent myocardial infarction
  • History of stroke
  • Known or suspected carotid artery stenosis

• Any contraindication to the Trendelenburg position, including:

  • Increased intracranial pressure
  • Respiratory distress
  • Congestive heart failure
  • History of syncope
  • History of cardiac arrhythmias

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A - Carotid Sinus Massage + Trendelenburg (CSM+T); Participants will receive carotid sinus massage (CSM) while positioned in a 10-15° Trendelenburg position. The massage is applied to the carotid sinus area for approximately 5 seconds and may be repeated up to three times, separated by one-minute intervals. Pain intensity and vital signs are assessed before and after the intervention.	Procedure: Arm A - Carotid Sinus Massage + Trendelenburg (CSM+T); Manual stimulation of the carotid sinus area combined with head-down tilt positioning to activate baroreceptors for headache relief.
Sham Comparator: Arm B - Sham CSM+T; In the control group, patients will be placed in the supine position. Then, a sham neck massage will be performed by lightly touching the skin in a circular motion away from the carotid sinus, for the same duration and intervals as in the experimental procedure. This sham approach will ensure that any observed effects are attributable to carotid sinus stimulation rather than mere tactile stimulation of the neck. Participants who do not report pain relief after the sham procedure will be offered rescue therapy, which may include the real CSM+Trendelenburg intervention or pharmacologic treatment, as clinically appropriate. The rescue response will be recorded for secondary analysis.	Procedure: Arm B - Sham CSM+T; Light neck contact, avoiding carotid sinus pressure, paired with identical body positioning to mimic the experimental intervention.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in headache pain intensity	Change in self-reported pain intensity using a 10-point Visual Analog Scale (VAS)	Baseline to 15 minutes post-intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in blood pressure	Difference in systolic and diastolic blood pressure (mmHg) from baseline to 15 minutes after the intervention.	Baseline to 15 minutes post-intervention
Change in heart rate	Difference in heart rate (beats per minute) measured before and after the intervention to assess autonomic or cardiovascular effects of the treatment.	Baseline to 15 minutes post-intervention
Change in oxygen saturation	Difference in peripheral oxygen saturation (SpO₂, %) measured by pulse oximetry before and after the intervention.	Baseline to 15 minutes post-intervention
Headache recurrence rate	Proportion of participants who experience recurrence of headache symptoms within 24 hours following the intervention.	24 hours post-intervention
Incidence of adverse events	Number and type of adverse events reported within 24 hours of the intervention, including any hemodynamic instability, discomfort, or other complications.	Up to 24 hours post-intervention
Percentage of participants with complete pain relief (VAS = 0)	Proportion of participants reporting a Visual Analog Scale (VAS) pain score of 0-indicating complete headache relief-15 minutes after the intervention. VAS scores range from 0 (no pain) to 10 (worst possible pain)	15 minutes post-intervention

Collaborators and Investigators

• Sponsor: Hospital Municipal Pedro T. Orellana
• Collaborators: Duke University Medical Center, Durham, NC
• Investigators: Principal Investigator: Pablo D Anaya, MD, Hospital Municipal Pedro T. Orellana; Study Director: Heberto J Suarez-Roca, MD, PhD, Dule University Medical Center, Dept. of Anesthesiology, Center for Translational Pain Medicine

Study record dates

Study Major Dates

• Study Start (Actual): December 21, 2024
• Primary Completion (Estimated): December 30, 2025
• Study Completion (Estimated): December 30, 2025

Study Registration Dates

• First Submitted: December 13, 2024
• First Submitted That Met QC Criteria: December 17, 2024
• First Posted (Actual): December 20, 2024

Study Record Updates

• Last Update Posted (Actual): June 15, 2025
• Last Update Submitted That Met QC Criteria: June 11, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Autonomic Nervous System; Trendelenburg; Carotid Sinus Massage
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Headache; Tension-Type Headache
• Other Study ID Numbers: HMPTOrellana

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) related to study outcomes will be shared, including pain scores, physiological measurements (such as heart rate, blood pressure, and oxygen saturation), and adverse event reports. Data will be made available upon reasonable request after publication of the primary results.
• IPD Sharing Time Frame: IPD will be made available beginning 6 months after publication of the primary results and will remain available for a minimum of 5 years thereafter.
• IPD Sharing Access Criteria: Qualified researchers may request access to the data by submitting a data use proposal, which should include a brief description of the study objectives and statistical plan. Requests will be reviewed by the study investigators or a designated data access committee. Data will be shared via secure transfer methods, subject to a data use agreement, to ensure participant confidentiality.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No