Tic DisordersNCT05263414
Neuromodulation of Inhibitory Control in Tic Disorders
A study testing tVNS in people with Tic Disorders, run by IRCCS Eugenio Medea at 1 site in Italy.
Trial summary
The present study aims to assess the effects of non invasive electrical stimulation of the vagus nerve via transcutaneous vagus nerve stimulation (tVNS) on cognitive functions, inhibitory and tic control in patients with tic disorders. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Tic Disorders
- What is being tested?
- tVNS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 26 participants
- Where
- 1 siteItaly
- Study dates
- 1 Jun 2022to 30 Apr 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- adults who aged 18-50 years;
- Diagnosis of Tic disorders
Who cannot join
- Presence of contraindication to tVNS (history of epilepsy in the last two years, severe brain trauma; presence of metal in the brain/skull or implanted neurostimulator, cardiac pacemaker; state of pregnancy);
- Recent changes in drugs therapy due to the intake of or the withdrawal from some drugs potentially changing the seizure threshold;
- Presence of comorbidity with an important medical condition;
- Severe sensorial, motor and/or behavioural problems that could interfere with the tasks
Trial locations and contacts
1 site in 1 country.
Italy1 site
Scientific Institute, IRCCS E. Medea,
Pasian di Prato, Udine, 33037
Alessandra Finisguerra, PhD, +390432693111, alessandra.finisguerra@lanostrafamiglia.it
Cosimo Urgesi, cosimo.urgesi@uniud.it
About this study
Official title: Modulation of Neurocognitive Mechanisms Involved in Inhibitory Control in Tic Disorders
The present study aims to assess the effects of non invasive electrical stimulation of the vagus nerve via transcutaneous vagus nerve stimulation (tVNS) on cognitive functions, inhibitory and tic control in patients with tic disorders. Taking into account the role that GABA plays in inhibitory control, the presence of alteration of GABA neurotransmission in Tic disorders and the possibility to increase GABA release with tVNS, the investigators hypothesized that tVNS might improve behavioral control in Tic disorders. Moreover, as suggested by previous studies investigating the effects of tVNS in other patient populations, the investigators expected that tVNS will be safe and well tolerated. Such results would encourage the use of tVNS in Tic disorders.
Read the detailed description
The investigators planned a single centre, randomized, double-blind, sham- controlled, crossover (within subject) design.
Adults with Tic Disorders will be recruited and randomly assigned to two different groups: the active-tVNS group and the sham-tVNS group. Each group will undergo a two-sessions intervention during which active tVNS followed by sham tVNS or sham tVNS followed by active tVNS will be delivered in the active and sham tVNS group, respectively. The stimulation will be delivered during the execution of an inhibitory task and an attentional task. For the inhibitory task a Contextual Go No-Go paradigm will be used. During this task, participants will be presented with visual stimuli representing everyday actions embedded within congruent or incongruent context. For example, stimuli could consist in precision or grasping actions suggesting the intention to eat or to move the object in another place. For each stimulus, there will be a kinematic component consisting in the movement performed by the model and a contextual component, consisting in the embedding scenario of the action (a breakfast scenario, or a cleaning scenario). Participants will be instructed to press a button when a specific intention (go) will be suggested by the video and not to press a button for the opposite intention (no go), either according to the kinematics or to the context, depending on the experimental block. This way, it will be possible to assess inhibitory control at response level. Crucially, kinematics and context of the visual stimuli could point toward the same (congruent) or opposite (incongruent) intentions, thus allowing to assess inhibitory control at the stimulus level. For the attentional task, the attentional network test (ANT; Fan et al.,2002) will be used. The task is a modified version of a Flanker task and it allows measuring orienting, alerting and executive control components. To assess the clinical, neuropsychological and behavioural profiles, the Yale Global Tic Severity Rating Scale (YGTSS), the EuroQol quality of life questionnaire, the Raven Matrix, the Autism Quotient, the Barratt Impulsiveness scale and the Navon Task will be used. The effects of tVNS on patients' behavioural control (as assessed through the Contextual Go No-Go task and the ANT) will be related to clinical, neuropsychological and behavioural profile, for identifying best the features tVNS responder patients. Side effects will be tested after each session.
The protocol will allow testing the efficiency of tVNS in:
- enhancing inhibition at response level (response selection) in Tic disorders;
- enhancing inhibition at stimulus level (response inhibition) in Tic disorders;
- improving alerting, orienting or executive control in Tic disorders;
- improving patients' quality of life and Tic control;
- further investigating the safety and tolerability of tVNS.
- Conditions
- Tic Disorders
- Being tested
- tVNS
- Keywords
- Transcutaneous vagus nerve stimulation, Tic disorders, Tourette syndrome, Inhibition, Tic control
- Medical subject headings
- Tic Disorders, Tourette Syndrome, Inhibition, Psychological
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tVNSDevice
tVNS allows the non-invasive activation of the Vagus Nerve by delivering electrical pulses to the sensory afferent fibers of the auricular, thick-myelinated, branch of the vagus nerve in the outer ear. TVNS seems to engage the same neural pathways of invasive VNS methods and may provide a novel, bottom-up NIBS method to promote GABA release. tVNS will be performed by using a CE marked tVNS device. It consists in a programmable stimulation unit connected to two titan ear electrodes that are mounted on a gel frame, allowing to generate and transfer electric impulses from the stimulation unit to the surface of the skin, where the electrodes are applied.
| Study group | Role | What they receive |
|---|---|---|
| Active tVNS | Active comparator | In the active tVNS session, tVNS will be delivered via a programmable stimulation unit connected to two titan ear electrodes mounted on a gel frame. Active tVNS will be delivered over the cymba conchae of the left ear for a 70 minutes session. Stimulation intensity will be set at an intensity corresponding to individual sensitivity threshold. The intensity of the stimulation will be gradually increased in order to reach the intensity of stimulation with a ramping-up phase of 30 secs. During the stimulation, participants will perform the tasks. At the end of the stimulation session participants will be asked to report possible side effects occurring during tVNS and to rate their feeling on several visual analogue scales. Receives: Device: tVNS |
| Sham tVNS | Sham comparator | In the sham tVNS session tVNS will be delivered via a programmable stimulation unit connected to two titan ear electrodes mounted on a gel frame. Sham tVNS will be delivered over the left lobe auricle area, which is free from cutaneous vagal innervation. It will last 70 minutes. Stimulation intensity will be set at the intensity corresponding to the individual sensitivity threshold, as it will be defined on the left ear lobe. The intensity of the stimulation will be gradually increased to reach the intensity of the stimulation with a ramping up phase of 30 secs. During the sham stimulation, the tasks will be performed. At the end of the stimulation session participants will be asked to report possible side effects occurring during tVNS and to rate their feeling on several visual analogue scales. Receives: Device: tVNS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Contextual Go No-Go
Performance in the contextual go no go task, consisting in the accuracy in making the response in the presence of a go stimulus, and not responding in the presence of a no-go stimulus (Response selection) as a function of different level of congruency between the kinematics and the contextual cues (stimulus selection). Change in inhibition at response level (response selection) and at stimulus level (response inhibition) after active tVNS.
Measured: Time 1- at the end the active session vs Time 0- at the end of the sham session
Attentional Network Test
Performance in the ANT tasks, with respect to the three components: alerting, orienting, executive control. For the alerting component, the mean RT of the correct trials in the double-cues conditions will be subtracted from the mean RT of the no-cue condition. For the Orienting component, the effect will be calculated by subtracting the mean RT of the spatial cue condition from the mean RT of the central cue condition. For the executive control component, the effect will be obtained by subtracting the mean RT of the incongruent flanking condition from the mean RT of the congruent flanking condition.Change in alerting, orienting, executive control after active tVNS.
Measured: Time 1- at the end the active session vs Time 0- at the end of the sham session
Secondary outcomes (3)
Tic control
Scores in the YBTCCS after each session will be compared.
Measured: Time 1- at the end the active tVNS session vs Time 0- at the end of the sham session
tVNS feasibility
Evaluation of the number of dropouts: number of patients who renounce to complete the two sessions. Evaluation of the number of sessions completed per patient: total number of sessions performed in front of the total number proposed of two sessions
Measured: Time 1- at the end the active tVNS session vs Time 0- at the end of the sham session
tVNS acceptability
Ad-hoc questionnaire completed by participants to assess subjective evaluation of tVNS discomfort (10 cm Visual Analogue scales with higher values corresponding to greater discomfort).
Measured: Time 1- at the end the active tVNS session
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2022
- Study start1 Jun 2022 (estimated)
- Primary completion31 Mar 2023 (estimated)
- Study completion30 Apr 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Tic DisordersStudies of the same condition, open and under way.
- More trials run by IRCCS Eugenio MedeaThe sponsor's other registered studies.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 26 participants (estimated)
Sponsor and investigators
- Lead sponsor
- IRCCS Eugenio Medea
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05263414
- Sponsor's protocol ID
- 847
- Status last verified
- Feb 2022
- First submitted
- 21 Feb 2022
- Last updated
- 2 Mar 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Anonymized dataset will be availabe at https://osf.io/
Study at a glance
From the registry record, last updated by the sponsor on 2 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Modulation of Neurocognitive Mechanisms Involved in Inhibitory Control in Tic Disorders
- ClinicalTrials.gov ID
- NCT05263414
- Acronym / sponsor ID
- 847
- Conditions
- Tic Disorders
- Keywords
- Transcutaneous vagus nerve stimulation, Tic disorders, Tourette syndrome, Inhibition, Tic control
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 26 participants (estimated)
- Lead sponsor
- IRCCS Eugenio MedeaUniversity, hospital or other
- Study start
- 1 Jun 2022 (estimated)
- Primary completion
- 31 Mar 2023 (estimated)
- Study completion
- 30 Apr 2023 (estimated)
- First posted
- 2 Mar 2022 (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.
The present study aims to assess the effects of non invasive electrical stimulation of the vagus nerve via transcutaneous vagus nerve stimulation (tVNS) on cognitive functions, inhibitory and tic control in patients with tic disorders. Taking into account the role that GABA plays in inhibitory control, the presence of alteration of GABA neurotransmission in Tic disorders and the possibility to increase GABA release with tVNS, the investigators hypothesized that tVNS might improve behavioral control in Tic disorders. Moreover, as suggested by previous studies investigating the effects of tVNS in other patient populations, the investigators expected that tVNS will be safe and well tolerated. Such results would encourage the use of tVNS in Tic disorders.
Detailed description
The investigators planned a single centre, randomized, double-blind, sham- controlled, crossover (within subject) design.
Adults with Tic Disorders will be recruited and randomly assigned to two different groups: the active-tVNS group and the sham-tVNS group. Each group will undergo a two-sessions intervention during which active tVNS followed by sham tVNS or sham tVNS followed by active tVNS will be delivered in the active and sham tVNS group, respectively. The stimulation will be delivered during the execution of an inhibitory task and an attentional task. For the inhibitory task a Contextual Go No-Go paradigm will be used. During this task, participants will be presented with visual stimuli representing everyday actions embedded within congruent or incongruent context. For example, stimuli could consist in precision or grasping actions suggesting the intention to eat or to move the object in another place. For each stimulus, there will be a kinematic component consisting in the movement performed by the model and a contextual component, consisting in the embedding scenario of the action (a breakfast scenario, or a cleaning scenario). Participants will be instructed to press a button when a specific intention (go) will be suggested by the video and not to press a button for the opposite intention (no go), either according to the kinematics or to the context, depending on the experimental block. This way, it will be possible to assess inhibitory control at response level. Crucially, kinematics and context of the visual stimuli could point toward the same (congruent) or opposite (incongruent) intentions, thus allowing to assess inhibitory control at the stimulus level. For the attentional task, the attentional network test (ANT; Fan et al.,2002) will be used. The task is a modified version of a Flanker task and it allows measuring orienting, alerting and executive control components. To assess the clinical, neuropsychological and behavioural profiles, the Yale Global Tic Severity Rating Scale (YGTSS), the EuroQol quality of life questionnaire, the Raven Matrix, the Autism Quotient, the Barratt Impulsiveness scale and the Navon Task will be used. The effects of tVNS on patients' behavioural control (as assessed through the Contextual Go No-Go task and the ANT) will be related to clinical, neuropsychological and behavioural profile, for identifying best the features tVNS responder patients. Side effects will be tested after each session.
The protocol will allow testing the efficiency of tVNS in:
- enhancing inhibition at response level (response selection) in Tic disorders;
- enhancing inhibition at stimulus level (response inhibition) in Tic disorders;
- improving alerting, orienting or executive control in Tic disorders;
- improving patients' quality of life and Tic control;
- further investigating the safety and tolerability of tVNS.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active tVNS | Active comparator | Device: tVNSIn the active tVNS session, tVNS will be delivered via a programmable stimulation unit connected to two titan ear electrodes mounted on a gel frame. Active tVNS will be delivered over the cymba conchae of the left ear for a 70 minutes session. Stimulation intensity will be set at an intensity corresponding to individual sensitivity threshold. The intensity of the stimulation will be gradually increased in order to reach the intensity of stimulation with a ramping-up phase of 30 secs. During the stimulation, participants will perform the tasks. At the end of the stimulation session participants will be asked to report possible side effects occurring during tVNS and to rate their feeling on several visual analogue scales. |
| Sham tVNS | Sham comparator | Device: tVNSIn the sham tVNS session tVNS will be delivered via a programmable stimulation unit connected to two titan ear electrodes mounted on a gel frame. Sham tVNS will be delivered over the left lobe auricle area, which is free from cutaneous vagal innervation. It will last 70 minutes. Stimulation intensity will be set at the intensity corresponding to the individual sensitivity threshold, as it will be defined on the left ear lobe. The intensity of the stimulation will be gradually increased to reach the intensity of the stimulation with a ramping up phase of 30 secs. During the sham stimulation, the tasks will be performed. At the end of the stimulation session participants will be asked to report possible side effects occurring during tVNS and to rate their feeling on several visual analogue scales. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- adults who aged 18-50 years;
- Diagnosis of Tic disorders
Key exclusion criteria (4 listed)
- Presence of contraindication to tVNS (history of epilepsy in the last two years, severe brain trauma; presence of metal in the brain/skull or implanted neurostimulator, cardiac pacemaker; state of pregnancy);
- Recent changes in drugs therapy due to the intake of or the withdrawal from some drugs potentially changing the seizure threshold;
- Presence of comorbidity with an important medical condition;
- Severe sensorial, motor and/or behavioural problems that could interfere with the tasks
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 |
|---|---|---|
| tVNStVNS allows the non-invasive activation of the Vagus Nerve by delivering electrical pulses to the sensory afferent fibers of the auricular, thick-myelinated, branch of the vagus nerve in the outer ear. TVNS seems to engage the same neural pathways of invasive VNS methods and may provide a novel, bottom-up NIBS method to promote GABA release. tVNS will be performed by using a CE marked tVNS device. It consists in a programmable stimulation unit connected to two titan ear electrodes that are mounted on a gel frame, allowing to generate and transfer electric impulses from the stimulation unit to the surface of the skin, where the electrodes are applied. | Device | Active tVNS, Sham tVNS |
Primary outcome
Contextual Go No-Go
Time frame: Time 1- at the end the active session vs Time 0- at the end of the sham session
Performance in the contextual go no go task, consisting in the accuracy in making the response in the presence of a go stimulus, and not responding in the presence of a no-go stimulus (Response selection) as a function of different level of congruency between the kinematics and the contextual cues (stimulus selection). Change in inhibition at response level (response selection) and at stimulus level (response inhibition) after active tVNS.
Attentional Network Test
Time frame: Time 1- at the end the active session vs Time 0- at the end of the sham session
Performance in the ANT tasks, with respect to the three components: alerting, orienting, executive control. For the alerting component, the mean RT of the correct trials in the double-cues conditions will be subtracted from the mean RT of the no-cue condition. For the Orienting component, the effect will be calculated by subtracting the mean RT of the spatial cue condition from the mean RT of the central cue condition. For the executive control component, the effect will be obtained by subtracting the mean RT of the incongruent flanking condition from the mean RT of the congruent flanking condition.Change in alerting, orienting, executive control after active tVNS.
3 secondary outcomes
Tic control
Time frame: Time 1- at the end the active tVNS session vs Time 0- at the end of the sham session
tVNS feasibility
Time frame: Time 1- at the end the active tVNS session vs Time 0- at the end of the sham session
tVNS acceptability
Time frame: Time 1- at the end the active tVNS session
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Mar 2022.
- Individual participant dataSharing planned: Yes. Anonymized dataset will be availabe at https://osf.io/
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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. This study is not recruiting at the moment.
Scientific Institute, IRCCS E. Medea,
Pasian di Prato, Italy
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing tVNS in people with Tic Disorders, run by IRCCS Eugenio Medea at 1 site in Italy.
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 2 inclusion and 4 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: status not confirmed, as of the sponsor's last update on 2 Mar 2022. 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 Italy. 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. Some participants in this study may receive a placebo. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Contextual Go No-Go (time frame: Time 1- at the end the active session vs Time 0- at the end of the sham session). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 Mar 2022.