Clinical trial NCT05086380: Modulation of Sense of Agency With Non-invasive Brain Stimulation and Mindfulness-based Stress Reduction Therapy
Official title: Modulation of the Sense of Agency Across Different Neurological Disorders Using Non-invasive Brain Stimulation and Mindfulness-based Stress Reduction Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Functional Neurological Symptom Disorder
Neurological Diseases or Conditions
Lead sponsor: University of Fribourg
Sponsor class: OTHER
Collaborators: name: Insel Gruppe AG, University Hospital Bern
First posted: 2021-10-20
Enrollment: 190
Sex: ALL
Minimum age (years): 17
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: A conversion disorder is a dysfunction of the nervous system in which no structural damage can be demonstrated. However, it must be distinguished from other psychiatric disorders such as psychosis or depression. There are a variety of signs of the disease, such as muscle paralysis, uncontrolled tremors or cramps. In rarer cases, blindness, deafness or numbness may occur. Diagnosing this complex disorder has always been a challenge for neurologists and psychiatrists.

This study investigates the effects of transcranial magnetic stimulation (TMS) on the general well-being and symptoms of conversion disorder and other neurological disorders and in comparison to healthy subjects. The TMS method allows to target specific areas of the brain by means of magnetic fields. This technique is not painful and does not have long-lasting effects.

In addition, the study investigates the effects of mindfulness-based stress reduction on the general well-being and symptoms of conversion disorder and other neurological disorders and compared to healthy subjects. This technique is not painful and has no long-lasting effects.

Furthermore, the study examines movement patterns and symptoms of patients compared to healthy controls while they are in a virtual reality.

Finally, the study examines patients' brain activity while playing a game targeting the sense of agency in real time, which is recorded with an MRI scanner.

The study includes a maximum of twelve sessions in total (ten sessions of approximately 1.5-2 hours each and two sessions each overnight). The planned study methods include TMS, (real-time and normal) magnetic resonance tomography of the brain (MRI "tube"), virtual- and augmented reality (AR/VR), questionnaires, blood, saliva, and motion sensors (e.g., fitness bracelet), and participation in the 8-week mindfulness program.


Eligibility criteria: Inclusion Criteria:

Patients:

* A diagnosis of a functional disorder (such as FND, GTS, PPD, anxiety or depression or others) according to DSM-5 diagnostic and ICD-11 criteria, or
* A diagnosis of an organic neurological disorder such as stroke, multiple sclerosis (MS), neuromuscular, or movement disorder
* Aged \> 16 years old
* Willing to participate in the study (by signing the ICF)
* Capable of judgement

healthy controls:

* Aged \> 16 years old
* Willing to participate in the study (by signing the ICF)
* Capable of judgement

Exclusion Criteria:

* Presence of comorbid psychiatric disorders such as psychosis, current major and severe depression episode, autistic spectrum disorder
* Past surgery in the brain
* History of alcohol or drug abuse
* Botulinum toxin injection in last 3 month
* Inability to follow the procedure of the study, e.g., due to language problems
* For organic disorders only: Active severe aphasia, dementia, neglect and acute confusional state, severe pain
* For female participants: breastfeeding, pregnancy or intention to become pregnant (assessed with standard urine test prior to the enrolment in the experiment and before each visit)
* For MRI and TMS part only: Past surgery in the brain
* For MRI and TMS part only: Implanted medical devices not-compatible with MRI or TMS (e.g., cochlear implants, infusion pumps, neurostimulators, cardiac pacemakers)
* For TMS part only: History of actual or suspected epilepsy
* For TMS part only: Suspected or diagnosed labile or hypertensive blood pressure
* For Virtual Reality only: No cybersickness

Primary outcomes:
measure: Change in objective Performance Agency Task (TMS)
timeFrame: Visit 1 (at baseline), visit 2 (one week after baseline), visit 3 (two weeks after baseline), visit 7 to 11 (12 - 16 weeks)
measure: Change in subjective Performance Agency Task (TMS)
timeFrame: Visit 1 (at baseline), visit 2 (one week after baseline), visit 3 (two weeks after baseline), visit 7 to 11 (12 - 16 weeks)
measure: Change in objective Performance Agency Task (MBSR)
timeFrame: Visit 4 (at least 1 week after visit 3), visit 5 (8 weeks after visit 4), visit 7 to 11 (12 - 16 weeks)
measure: Change in subjective Performance Agency Task (MBSR)
timeFrame: Visit 4 (at least 1 week after visit 3), visit 5 (8 weeks after visit 4), visit 7 to 11 (12 - 16 weeks)
Secondary outcomes:
measure: task-based fMRI measures TMS
timeFrame: Visit 1 (at baseline), visit 2 (one week after baseline), visit 3 (two weeks after baseline)
measure: resting-state fMRI measures TMS
timeFrame: Visit 1 (at baseline), visit 2 (one week after baseline), visit 3 (two weeks after baseline)
measure: DTI measures TMS
timeFrame: Visit 1 (at baseline), visit 2 (one week after baseline), visit 3 (two weeks after baseline)
measure: task-based fMRI measures MBSR
timeFrame: Visit 4 (at least 1 week after visit 3), visit 5 (8 weeks after visit 4)
measure: resting-state fMRI measures MBSR
timeFrame: Visit 4 (at least 1 week after visit 3), visit 5 (8 weeks after visit 4)
measure: DTI measures MBSR
timeFrame: Visit 4 (at least 1 week after visit 3), visit 5 (8 weeks after visit 4)
measure: Subjective Agency TMS
timeFrame: Visit 1 (at baseline), visit 2 (one week after baseline), visit 3 (two weeks after baseline)
measure: Subjective Agency MBSR
timeFrame: Visit 4 (at least 1 week after visit 3), visit 5 (8 weeks after visit 4)
measure: Neurological Examination TMS
timeFrame: Visit 1 (at baseline), visit 2 (one week after baseline), visit 3 (two weeks after baseline)
measure: Neurological Examination MBSR
timeFrame: Visit 4 (at least 1 week after visit 3), visit 5 (8 weeks after visit 4)
measure: Objective stress parameters pre/post
timeFrame: Visit 4 (at least 1 week after visit 3), visit 5 (8 weeks after visit 4)
measure: Subjective stress parameters pre/post
timeFrame: Visit 4 (at least 1 week after visit 3), visit 5 (8 weeks after visit 4)
measure: Sleep
timeFrame: Visit 4 (at least 1 week after visit 3), visit 5 (8 weeks after visit 4)
measure: Neurofeedback
timeFrame: Visit 7 to 11 (12 - 16 weeks)
measure: Long-term effects on task-based fMRI measures MBSR
timeFrame: At follow-up (6 month after visit 5)
measure: Long-term effects on resting-state fMRI measures MBSR
timeFrame: At follow-up (6 month after visit 5)
measure: Long-term effects on DTI measures MBSR
timeFrame: At follow-up (6 month after visit 5)
measure: Long-term effects on subjective agency MBSR
timeFrame: At follow-up (6 month after visit 5)
measure: Long-term effects on neurological examination MBSR
timeFrame: At follow-up (6 month after visit 5)
measure: Long-term effects on objective performance
timeFrame: At follow-up (6 month after visit 5)
measure: Long-term effects on subjective performance
timeFrame: At follow-up (6 month after visit 5)
measure: Neurophysiological measures: MEP
timeFrame: Visit 1 (at baseline), visit 2 (one week after baseline), visit 3 (two weeks after baseline), visit 4 (at least 1 week after visit 3), visit 5 (8 weeks after visit 4) and follow up (6 month after visit 5)
measure: Neurophysiological measures: MT
timeFrame: Visit 1 (at baseline), visit 2 (one week after baseline), visit 3 (two weeks after baseline), visit 4 (at least 1 week after visit 3), visit 5 (8 weeks after visit 4) and follow up (6 month after visit 5)
measure: Neurophysiological measures: SICI
timeFrame: Visit 1 (at baseline), visit 2 (one week after baseline), visit 3 (two weeks after baseline), visit 4 (at least 1 week after visit 3), visit 5 (8 weeks after visit 4) and follow up (6 month after visit 5)
measure: Neurophysiological measures: LICI
timeFrame: Visit 1 (at baseline), visit 2 (one week after baseline), visit 3 (two weeks after baseline), visit 4 (at least 1 week after visit 3), visit 5 (8 weeks after visit 4) and follow up (6 month after visit 5)
measure: Neurophysiological measures CSP
timeFrame: Visit 1 (at baseline), visit 2 (one week after baseline), visit 3 (two weeks after baseline), visit 4 (at least 1 week after visit 3), visit 5 (8 weeks after visit 4) and follow up (6 month after visit 5)
measure: Neurophysiological measures: PAS
timeFrame: Visit 1 (at baseline), visit 2 (one week after baseline), visit 3 (two weeks after baseline), visit 4 (at least 1 week after visit 3), visit 5 (8 weeks after visit 4) and follow up (6 month after visit 5)
measure: Epigenetic profile
timeFrame: 1st visit (baseline)
measure: Long-term fluctuations of objective stress parameters
timeFrame: at follow-up (6 month after visit 5)
measure: Long-term fluctuations of subjective stress parameters
timeFrame: at follow-up (6 month after visit 5)
measure: Position of focus of attention
timeFrame: at visit 6 (at least one week after visit 5)
measure: Kinematics of limb movements
timeFrame: at visit 6 (at least one week after visit 5)
measure: Stability
timeFrame: Visit 1 (at baseline), and follow up (8 month after visit 1)
measure: Cognition
timeFrame: Visit 1 (at baseline), and follow up (8 month after visit 1)
measure: Pain processing
timeFrame: Visit 1 (at baseline), and follow up (8 month after visit 1)
Other outcomes:
Locations:
city: Fribourg
country: Switzerland
facility: University of Fribourg
Study officials:
affiliation: University of Fribourg
name: Selma Aybek, MD
role: PRINCIPAL_INVESTIGATOR
References: