Olfactory Stimulation in Severe Brain Injury

NCT05747170 | Completed

• 1 other identifier: 4376
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The management of patients with disorders of consciousness (DoC) represents a topic of great importance and topicality in the medical-scientific field because of the complexity and extent of associated disabilities and the difficulty in identifying effective therapeutic approaches. Despite significant advances in neuroscience, much remains to be elucidated about the mechanisms that regulate consciousness, and which of these to act on to stimulate plasticity and thus promote responsiveness and functional recovery in patients. Evidence on treatments that promote arousal and communication skills in individuals with DoC is still limited. Among the possible interventions proposed in the literature, sensory stimulation would act by stimulating synaptic plasticity, counteracting the sensory deprivation to which these patients are exposed. Published studies on the topic have produced results that are not unique and difficult to compare across different stimulation protocols (content, intensity, frequency, modality), settings and patient populations.

Conditions

Disorder of Consciousness

Keywords

Acquired Brain Injury; Disorder of Consciousness; Olfactory stimulation

Outcome Measures

Primary Outcomes (1)

• Sympathetic Skin Response (SSR)

  SSR is a physiologic measurement to record the electrical potential through an electrode placed on the palm of the hand after median nerve stimulation. The test is based on the temporary change in skin electrical resistance in response to activation of the sweat glands when exposed to a stimulus. It allows assessment of the ANS response through the study of sympathetic cholinergic efferent pathways

  Change from baseline SSR at 2 weeks

Secondary Outcomes (4)

• Electrodermal Activity (EDA)

  Change from baseline EDA at 2 weeks

• Heart Rate Variability (HRV)

  Change from baseline HRV at 2 weeks

• Electrocortical activity

  Change from baseline EEG-HD at 2 weeks

• Coma Recovery Scale-revised

  Change from baseline CRS-r at 2 weeks

Study Arms (2)

Group natural_neutral_chemical

EXPERIMENTAL

The recruited subjects (DoC patients and healthy subjects) will be evaluated inside a quiet, well-ventilated room and will be subjected to olfactory stimulation using odors with different characteristics a "natural" type odor, e.g., mint, a "chemical" type odor, e.g., gasoline, and a "neutral" type odor, e.g., water. Stimulation will have, for each odor the duration of 5 minutes. It will always be carried out within the same time slot (between 8:00 am and 4:00 pm) for 5 consecutive days for 2 weeks. Before and after the administration of each odor, a neutral odor (water) will be administered as a control in the same manner as described above. The sequence of odor administration will be: natural odor (mint) for 5 minutes, neutral odor (water) for 5 minutes, chemical odor (gasoline) for 5 minutes.

Other: Olfactory sstimulation

Group chemical:neutral_natural

EXPERIMENTAL

The recruited subjects (DoC patients and healthy subjects) will be evaluated inside a quiet, well-ventilated room and will be subjected to olfactory stimulation using odors with different characteristics a "natural" type odor, e.g., mint, a "chemical" type odor, e.g., gasoline, and a "neutral" type odor, e.g., water. Stimulation will have, for each odor the duration of 5 minutes. It will always be carried out within the same time slot (between 8:00 am and 4:00 pm) for 5 consecutive days for 2 weeks. Before and after the administration of each odor, a neutral odor (water) will be administered as a control in the same manner as described above. The sequence of odor administration will be: chemical odor (gasoline) for 5 minutes, neutral odor (water) for 5 minutes, natural odor (mint) for 5 minutes.

Other: Olfactory sstimulation

Interventions

Olfactory sstimulation OTHER

The odors being tested (natural odor, neutral odor, chemical odor) are part of the 40 fragrances made by International Flavors and Fragrances (IFF) and each is contained in an approximately 15-mL glass bottle. The selected odors will be administered using a small paper strip (15 cm length and 0.7 cm width) that will be soaked in the selected odor and placed under the subject's nose at a minimum distance to prevent direct contact of the strip with the skin; the strip will be moved alternately from one nostril to the other. Stimulation will have, for each odor the duration of 5 minutes. It will always be carried out within the same time slot (between 8:00 am and 4:00 pm) for 5 consecutive days for 2 weeks. Before and after the administration of each odor, a neutral odor (water) will be administered as a control in the same manner as described above. The sequence of odor administration will be randomized according to a computer-generated sequence.

Group chemical:neutral_natural; Group natural_neutral_chemical

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 18 and 90 years;
• Glasgow Come Scale (GCS) score between 8 and 13;
• Level of Cognitive Function (LCF) score between 2 and 3;
• Latency from the acute event of not more than 2 months;
• Spontaneous eye opening.

You may not qualify if:

• Documented history of brain injury prior to the one that resulted in hospitalization;
• Documented history of uncorrected visual or hearing impairment;
• Documented history of chronic rhinosinusitis with or without the presence of naso-sinus polyps;
• Previous history of psychiatric and/or neurological disorders that resulted in significant disability prior to the acute event;
• Acute pathology at the time of recruitment, head injury, or ischemic or expansive injury with suspected peripheral olfactory tract involvement.

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead

Study Sites (1)

Fondazione Policlinico Universitario A. Gemelli IRCCS

Roma, RM, 00168, Italy

Location

MeSH Terms

Conditions

Consciousness Disorders; Brain Injuries

Condition Hierarchy (Ancestors)

Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders; Brain Diseases; Central Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Study Officials

• Luca Padua, MD, phD

  Fondazione Policlinico Universitario A. Gemelli, IRCCS

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 17, 2023
• First Posted: February 28, 2023
• Study Start: October 15, 2021
• Primary Completion: April 30, 2022
• Study Completion: June 30, 2024
• Last Updated: March 20, 2025

Record last verified: 2024-02

Locations

IT (1)