Tickle Stimulation in Disorders of Consciousness (DoC) (TICKLING-DOC)

Behavioural and Physiological Responses to Tickling in Patients With Disorders of Consciousness

The aim of this project is to investigate whether tickling stimulations can have a short-term effect on the responsiveness of patients with Disorders of Consciousness due to Severe Acquired Brain Injury and to compare this effect with that of neutral tactile stimulations that do not induce tickling.

Study Overview

• Status: Recruiting
• Conditions: Disorders of Consciousness
• Intervention / Treatment: Behavioral: Tickle stimulation; Device: Neurophysiological Monitoring with SedLine

Detailed Description

During the experimental session, patients will undergo the CRS-R and the Nociception Coma Scale-Revised (NCS-R) to ensure that any responses to tickling are not influenced by pain sensations. Subsequently, fNIRS detection optodes will be placed using a non-invasive frontal headband. A 10-minute resting-state recording will be performed. Next, patients will be subjected to tickling: they will be tickled bilaterally in the three most ticklish areas identified in a pilot study with healthy subjects-namely, the soles of the feet, the armpits, and the ribs-plus a control area, the forehead. The stimulation will be manual and will be performed by rubbing the targeted body part while opening and closing fingers in pairs in an arched motion. Additionally, patients will also receive a neutral stimulation (in the same body areas), which consists of simply touching the area without inducing tickling. The order of stimulations will follow a randomized list. Each stimulation will last for 5 seconds, followed by 5 seconds of rest, repeated twice. In total, patients will be stimulated for 10 seconds plus 5 seconds of rest (15 seconds in total) for each body area. There will be a 1-minute pause between each area. Afterward, an additional 10 minute resting-state fNIRS recording will be conducted. During the experimental session, patients will be filmed so that the videos can be analyzed by two different experimenters, who will assess differences between stimulations based on facial expressions, verbalizations/vocalizations, body movements, and changes in emotional state (e.g., crying, smiling, grimacing). At the end of the protocol, the fNIRS optodes will be removed. In total, the experiment will last approximately one hour and fifteen minutes: 30 minutes for CRS-R/NCS-R and 45 minutes for the tickling protocol and fNIRS recording.

• Study Type: Observational
• Enrollment (Estimated): 45

Contacts and Locations

• Study Contact: Name: Simona Abagnale, PhD; Phone Number: +393487520258; Email: sabagnale@dongnocchi.it

Study Locations

• Belgium
  • Liege, Belgium, 4000
    • Completed
    • Coma Science Group - University of Liege
• Italy
  • Avellino
    • Sant'Angelo dei Lombardi, Avellino, Italy, 83054
      • Recruiting
      • Fondazione Don Gnocchi

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

All patients with DoC who are consecutively admitted to the participating centers of the study.

Description

Inclusion Criteria:

• Diagnosis of disorders of consciousness (DoC) based on the CRS-R scale;
• Age ≥18 years;
• Time since the event ≥ 28 days

Exclusion Criteria:

• Large craniectomy that may interfere with fNIRS recording; Unstable clinical conditions (e.g., respiratory failure, fever, status epilepticus, etc.);
• Fractures, paralysis, injuries, or muscular dystrophy that prevent proper stimulation of the aforementioned body parts;
• Lack of informed consent from the legal representative.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Patients with Disorders of Consciousness (DoC); All patients with disorders of consciousness who are consecutively admitted to the participating centers of the study will be enrolled with a diagnosis of disorders of consciousness based on the CRS-R scale, with an age ≥18 years and a time since the event ≥ 28 days.

Behavioral: Tickle stimulation; Patients will be subjected to tickling: they will be tickled bilaterally in three areas, the soles of the feet, the armpits, and the ribs-plus a control area, the forehead. The stimulation will be manual and performed by rubbing the targeted body part while opening and closing the fingers in pairs in an arched motion. Additionally, patients will also undergo a neutral stimulation (in the same body areas), which consists of simply touching the area without inducing tickling.; Device: Neurophysiological Monitoring with SedLine; SedLine is a portable, non-invasive EEG monitoring device used to record electrical brain activity through frontal electrodes. In the TICKLING-DOC study, SedLine is used to assess cortical responses in patients with disorders of consciousness (DoC) during manual tactile stimulation, specifically tickling, and neutral touch. The EEG data are recorded before, during, and after stimulation to detect neural reactivity and possible correlations with behavioral responses. The goal is to investigate whether tickle-evoked EEG activity reflects residual consciousness and contributes to diagnostic and rehabilitative strategies. SedLine allows continuous monitoring in a bedside setting, offering safe, real-time assessment of brain function.; Other Names: SedLine EEG Monitor; Masimo SedLine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Behavioral Response Scores During Tickling and Neutral Stimulation (Video Coding)	Behavioral responses will be evaluated from video recordings by two blinded raters, based on predefined observational categories (e.g., facial expressions, vocalizations, etc).	Day 1 (single session)
Hemodynamic Response Changes Measured by fNIRS During Tickling and Neutral Stimulation	Oxygenated and deoxygenated hemoglobin changes (HbO/HbR) will be recorded using functional near-infrared spectroscopy (fNIRS) in response to tactile stimulation. Signal changes in prefrontal regions will be analyzed and compared across stimulation types.	Day 1 (single session)
Cortical EEG Activation Patterns During Tickling and Neutral Stimulation (SedLine)	EEG data will be acquired with SedLine during stimulation sessions. Spectral power in defined frequency bands (e.g., alpha, beta) will be analyzed and compared between conditions.	Day 1 (single session)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Coma Recovery Scale-Revised (CRS-R) Total Score Prior to Tickling Stimulation	Coma Recovery Scale-Revised (CRS-R) total score assessed before the stimulation protocol to determine baseline level of consciousness.The Coma Recovery Scale-Revised (CRS-R) is a standardized behavioral assessment tool used to determine the level of consciousness in patients with disorders of consciousness. Scores range from 0 to 23, with higher scores indicating better consciousness and functional responsiveness.	Day 1 (baseline)
Nociception Coma Scale-Revised (NCS-R) Total Score Prior to Stimulation	NCS-R will be administered before tactile stimulations to assess nociceptive reactivity. The Nociception Coma Scale-Revised (NCS-R) is a standardised behavioural tool used to assess nociceptive responses in patients with disorders of consciousness. It includes three subscales (motor, verbal, and facial responses). Scores range from 0 to 9, with higher scores indicating greater responsiveness to nociceptive stimuli.	Day 1 (baseline)

Collaborators and Investigators

• Sponsor: Anna Estraneo
• Investigators: Principal Investigator: Anna Estraneo, MD, Fondazione Don Gnocchi; Principal Investigator: Olivia Gosseries, PhD, Professor, University of Liege

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2023
• Primary Completion (Estimated): July 31, 2025
• Study Completion (Estimated): October 31, 2025

Study Registration Dates

• First Submitted: March 26, 2025
• First Submitted That Met QC Criteria: April 3, 2025
• First Posted (Actual): April 10, 2025

Study Record Updates

• Last Update Posted (Actual): April 23, 2025
• Last Update Submitted That Met QC Criteria: April 17, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Disorders of Consciousness; Behavioural evaluation; Tickle stimulation; Neurophysiological evaluation
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Neurobehavioral Manifestations; Neurocognitive Disorders; Consciousness Disorders
• Other Study ID Numbers: TICKLING-DOC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD collected throughout the trial (CRS-R, NCS-R, video recordings outcomes, fNIRS data)
• IPD Sharing Time Frame: From the first patient recording data until the last patient.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

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