Clinical trial NCT06689345: Effect of Non-Invasive Neuromodulation on Primary Chronic Pain, Including Post-COVID-19
Official title: Effects of Non-invasive Neuromodulation on Post-COVID-19 Syndrome: Multicenter Study
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: NA
Conditions: Post COVID Condition
Chronic Pain
Healthy
Keywords: neuromodulation
chronic pain
covid-19
TMS-EEG
vagal nerve
Lead sponsor: Federal University of ABC
Sponsor class: OTHER
Collaborators: name: University of Sao Paulo
name: Coordination for the Improvement of Higher Education Personnel
First posted: 2024-11-14
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: First, we will test the savety and effects of neuromodulation using four different tecniques on autonomous system of healthy people.

Then, we will test the effect of neuromodulation through, vagal stimulation, on pain, fatigue, mental healthy and disautonomy of people with primary chronic pain and/or post-COVID syndrom. For this, active and sham stimulations will be compared.
Primary purpose: TREATMENT

Brief summary: The aim of this study is to analyse whether there is an advantage in adding low-intensity electrical stimulations to the vagus nerve with electrodes in the outer ear to control pain and fatigue in people with primary chronic pain, and in people who have had COVID-19. Several studies have shown that many people with primary chronic pain and also people who have had COVID patients continue to have pain and fatigue that may be due to changes that occur in the brain and the vagus nerve that passes through the neck might cause inflammation. Therefore the aim of this study is to investigate if these electrical stimulations can help improve the condition of the brain and nerve and consequently, the inflammation so that these complaints improve.

This study will be organized as the following: It will begin with an assessment, divided into a part with questionnaires and another with specific tests. The questionnaires are aimed at understanding volunteer's characteristics, pain, fatigue, inflammation, sleep, quality of life, and the presence of symptoms of anxiety and depression. Next, the volunteer will undergo two tests to assess the behavior of his/her brain. They are performed using EEG electroencephalography and transcranial magnetic stimulation (TMS).

* Quantitative EEG at rest - In this technique, a cap with electrodes is placed on volunteer's head, in contact with hair, which are connected through a gel. The volunteer needs to remain still for 6 minutes with eyes closed, sitting in a comfortable chair.
* TMS with EEG - First, the volunteer will be asked to honestly answer the questions in the safety questionnaire for using this technique. Honest answers will eliminate the risks associated with this evaluation. Next, the volunteer's skin will be cleaned with alcohol and a special paste and place three self-adhesive electrodes on the muscle of the volunteer's hand, in a muscle called the interosseous, on the side where he/she writes. These electrodes will only capture the electrical activity of the muscle. Next, a series of magnetic pulses will be administered to the volunteer's skull, in the area that controls the hand muscle. It will contract with each pulse and, with this, so that the functioning of this connection can be understood. At the same time, the EEG device will capture the brain activities that occur during this TMS stimulation. During this exam, the volunteer may feel anything from no stimulation to muscle contractions that move his/her hand. Some people also experience redness under the electrodes, fatigue, or muscle/joint pain.

After the assessments, volunteers will be randomly selected to receive neuromodulation sessions using low-intensity electrical stimulation of the vagus nerve, using electrodes in the outer ear (active group), or sessions that only simulate this neuromodulation (sham, or placebo, group). This will occur for five consecutive days, starting on the day of the assessment. This stimulation is very weak and may not even be felt by the person receiving it. This technique is safe and the most that may occur is redness or itching of the skin. A few people may also experience tingling, a burning sensation or momentary local pain, fatigue, drowsiness, difficulty concentrating and a feeling of nervousness during or after the stimulation.

At the end of the 5 days of electrical stimulation, the same initial assessments will be repeated to see if anything has changed in the volunteer's brain, heart rate, blood pressure, pain, fatigue, inflammation, sleep, quality of life, depression, and anxiety.


Eligibility criteria: Inclusion Criteria:

* Healthy individuals, both sexes, aged between 18 and 40 years (first arm).
* Diagnosis of primary chronic pain (for more than 3 months), such as fibromyalgia (chronic widespread pain), primary chronic headache and orofacial pain, chronic primary visceral pain, post-COVID pain, and chronic primary musculoskeletal pain;
* In the case of post-COVID-19 pain, the symptoms must be present for at least 12 weeks. The complaints of pain, fatigue, and/or changes in mental health should have started after infection by SARS-Cov-2.

Exclusion Criteria:

* Individuals who present dysautonomia;
* obese individuals with a high abdominal fat index characterized by a waist/hip ratio of 0.80 for women and 0.95 for men;
* heart disease;
* diabetes mellitus;
* vestibular alterations characterized by the Dix-Hallpike maneuver, supine rotation test, arc test, side-lying maneuver, and post-head-shake nystagmus;
* diagnosis of epilepsy or first-degree family history of epilepsy
* fever;
* chronic consumption of alcohol, or other recreational drugs;
* presence of contraindications for the use of non-invasive neuromodulation;
* those who become ill with COVID-19 during the data collection period;
* those who are unable to answer the evaluation questionnaires;
* those with clinical instability;
* those who have a previous history of chronic pain or fatigue before contracting COVID-19;
* those who have neuropathic pain.

Primary outcomes:
measure: Pain
timeFrame: 5 days
Secondary outcomes:
measure: Heart rate variability and blood preasure
timeFrame: 5 days
measure: Pressure pain threshold.
timeFrame: 5 days
measure: TMS-Evoked potential
timeFrame: 5 days
measure: Disautonomy, fatigue and mental health
timeFrame: 5 days
Other outcomes:
Locations:
city: Sâo Bernardo do Campo
country: Brazil
facility: Federal University of ABC
state: Sao paulo
Study officials:
affiliation: Federal University of ABC
name: Tiago S Lopes, PhD
role: STUDY_CHAIR
References: