Study of Biomorkers and Rehabilitation Strategies in Functional Motor Disorders (FMD)

NCT06328790 | Recruiting

• 1 other identifier: PNRR-MAD-2022-12376826
• Study Type: observational
• Target: 450
• Locations: 1 country
• Sites: 3

Brief Summary

Functional motor disorders (FMD) are prevalent and highly disabling conditions characterized by abnormal movements (functional weakness, tremor, dystonia) significantly altered by distractive manoeuvres and incongruent with movement disorders seen in specific neurological diseases. FMDs are still misunderstood, diagnosed with delay, and not adequately treated, leading to reduced independence and high healthcare costs. Symptoms are physiologically associated with voluntary movement (distractibility, resolution with placebo) but are reported as involuntary. How this happens is yet a matter of debate. Identifying diagnostic and prognostic disease-specific biomarkers is an unmet need. The investigators will investigate motor, exteroceptive and interoceptive domains in a large cohort of FMD patients by a comprehensive set of behavioural, neurophysiological, and MRI tests. Ad-hoc eXplainable Artificial Intelligence (XAI) methods will develop disease-specific diagnostic and prognostic biomarker algorithms.

Conditions

Functional Motor Disorders

Keywords

Non motor symptoms; Motor symptoms; Exteroception; Interoception; Neurophysiological; MRI assessment; Diagnosis; Behavioral

Outcome Measures

Primary Outcomes (24)

• Simplified Functional Movement Disorders Rating Scale (S-FMDRS) score

  Objective-rated validated scale to rate the duration and severity of functional motor symptoms (range: 0-54; higher = worse).

  Before the intensive 5-day rehabilitation protocol (T0) and after 3 months of the intensive 5-day rehabilitation protocol (T1).

• Multidimensional Fatigue Inventory Scale (MFI-20) score

  It evaluates fatigue differentiating general, physical, reduced-activity, reduced-motivation, and mental fatigue (subscale range: 4-20; higher = worse).

  Before the intensive 5-day rehabilitation protocol (T0) and after 3 months of the intensive 5-day rehabilitation protocol (T1).

• Brief Pain Inventory (BPI) score

  It evaluates pain intensity (range: 0-40; higher = worse) and interference (range: 0-70; higher = worse).

  Before the intensive 5-day rehabilitation protocol (T0) and after 3 months of the intensive 5-day rehabilitation protocol (T1).

• Beck Anxiety Inventory (BAI) score

  It evaluates anxiety (range: 0-63; higher = worse).

  Before the intensive 5-day rehabilitation protocol (T0) and after 3 months of the intensive 5-day rehabilitation protocol (T1).

• Beck Depression Inventory (BDI-II) score

  It evaluates depression (range: 0-63; higher = worse).

  Before the intensive 5-day rehabilitation protocol (T0) and after 3 months of the intensive 5-day rehabilitation protocol (T1).

• 12-item Short-Form Health Survey (SF-12) score

  The health-Related QoL will be evaluated by the Mental Health and Physical functioning of the 12-item Short-Form Health Survey (SF-12) (range: 0-100; higher = better).

  Before the intensive 5-day rehabilitation protocol (T0) and after 3 months of the intensive 5-day rehabilitation protocol (T1).

• Toronto Alexithymia Scale (TAS-20) score

  It evaluates the level of alexithymia (range: 20-100; higher = worse).

  Before the intensive 5-day rehabilitation protocol (T0) and after 3 months of the intensive 5-day rehabilitation protocol (T1).

• Direct adn indirect index of Sensory Attenuation (SA)

  Sensory attenuation (SA) will be used to collect data

  Before the intensive 5-day rehabilitation protocol (T0) and after 3 months of the intensive 5-day rehabilitation protocol (T1).

• Joint angle at the elbow vibrated and reproduced

  Tonic vibration reflex (TVR) will be used to collect data

  Before the intensive 5-day rehabilitation protocol (T0) and after 3 months of the intensive 5-day rehabilitation protocol (T1).

• N2/P2 amplitude

  Laser evoked potentials (LEP) will be used to collect data

  Before the intensive 5-day rehabilitation protocol (T0) and after 3 months of the intensive 5-day rehabilitation protocol (T1).

• Objective/Subjective heart rate ratio

  Heartbeat Perception Task (HPT) will be used to collect data

  Before the intensive 5-day rehabilitation protocol (T0) and after 3 months of the intensive 5-day rehabilitation protocol (T1).

• Cortical thickness and gray matter volumes

  Brain 3 Tesla MRI will be used to collect data

  Before the intensive 5-day rehabilitation protocol (T0) and after 3 months of the intensive 5-day rehabilitation protocol (T1).

• Clinical Global Impression (CGI) score

  Self-rated perception of change will be assessed with the 7-point Clinical Global Impression (CGI) scale with scores from 1 (very much improved) to 7 (very much worse).

  After 3 months of the intensive 5-day rehabilitation protocol (T1).

• Gait speed (cm/sec)

  Gait analysis will be used to collect gait speed (cm/s).

  Before the intensive 5-day rehabilitation protocol (T0) and after 3 months of the intensive 5-day rehabilitation protocol (T1).

• Swing time (%)

  Gait analysis will be used to collect swing time (%).

  Before the intensive 5-day rehabilitation protocol (T0) and after 3 months of the intensive 5-day rehabilitation protocol (T1).

• Stride time (s)

  Gait analysis will be used to collect stride time (s).

  Before the intensive 5-day rehabilitation protocol (T0) and after 3 months of the intensive 5-day rehabilitation protocol (T1).

• Stride length (cm)

  Gait analysis will be used to collect stride length (cm).

  Before the intensive 5-day rehabilitation protocol (T0) and after 3 months of the intensive 5-day rehabilitation protocol (T1).

• Sway area (mm2)

  An electronic monaxial stabilometric platform will be used to collect sway area (mm2).

  Before the intensive 5-day rehabilitation protocol (T0) and after 3 months of the intensive 5-day rehabilitation protocol (T1).

• Stance time (sec)

  An electronic monaxial stabilometric platform will be used to collect stance time (sec).

  Before the intensive 5-day rehabilitation protocol (T0) and after 3 months of the intensive 5-day rehabilitation protocol (T1).

• Total excursion path (mm)

  An electronic monaxial stabilometric platform will be used to collect total excursion path (mm): area of oscillations of the Center of Pressure (CoP), CoP perimeter length

  Before the intensive 5-day rehabilitation protocol (T0) and after 3 months of the intensive 5-day rehabilitation protocol (T1).

• Velocity of Cop displacement in the anteroposterior directions (mm/s)

  An electronic monaxial stabilometric platform will be used to collect the velocity of Cop displacement in the anteroposterior directions.

  Before the intensive 5-day rehabilitation protocol (T0) and after 3 months of the intensive 5-day rehabilitation protocol (T1).

• Velocity of Cop displacement in the mediolateral directions (mm/s)

  An electronic monaxial stabilometric platform will be used to collect the velocity of Cop displacement in the mediolateral directions.

  Before the intensive 5-day rehabilitation protocol (T0) and after 3 months of the intensive 5-day rehabilitation protocol (T1).

• Autism spectrum Quotient (AQ)

  It is a 50-item self-report measure used to assess traits of autism in adults and adolescents aged 16 years and over (Total score: 0-50; cut-off: \> 29).

  Before the intensive 5-day rehabilitation protocol (T0)

• Schizotypal Personality Questionnaire (SPQ)

  It is a scale for the assessment of schizotypal personality based on DSM-III-R criteria (Total score: 0-74; cut-off: \< 8 \& \> 42).

  Before the intensive 5-day rehabilitation protocol (T0)

Other Outcomes (2)

• Number of drop-out

  Before the intensive 5-day rehabilitation protocol (T0) and after 3 months of the intensive 5-day rehabilitation protocol (T1).

• Number of patients who refuse the treatment

  Before the intensive 5-day rehabilitation protocol (T0) and after 3 months of the intensive 5-day rehabilitation protocol (T1).

Study Arms (4)

Functional Motor Disorder rehabilitation group (FMD)

Patients with FMD (subject to current diagnostic criteria) will undergo experiment 3.

Other: Multidisciplinary Rehabilitation Training

Healthy Controls group (HC)

Healthy subjects at least 18 years old will undergo experiment 1.

Behavioral: Cross-sectional study on patients with FMD and healthy controls (HC)

"Organic" Motor Disorders group

Patients with "organic" motor disorders (weakness due to peripheral neuromuscular disorders, essential tremor, or idiopathic adult-onset dystonia, all according to current diagnostic criteria) will undergo experiment 2.

Behavioral: Cross-sectional study on patients with FMD and patients with structural/organic diseases

Functional Motor Disorder group (FMD)

Patients with FMD (subject to current diagnostic criteria) will undergo experiment 1.

Behavioral: Cross-sectional study on patients with FMD and healthy controls (HC)

Interventions

Multidisciplinary Rehabilitation Training OTHER

34 Patients will attend the in-person 5-day rehabilitation program (2 h/day) followed by a 12-weeks telemedicine program (1 h/week).

Also known as: Experiment 3

Functional Motor Disorder rehabilitation group (FMD)

Cross-sectional study on patients with FMD and patients with structural/organic diseases BEHAVIORAL

Each subject will undergo behavioural, neurophysiological, and Magnetic Resonance Imaging (MRI) tests exploring the motor, exteroceptive and interoceptive domains.

Also known as: Experiment 2

"Organic" Motor Disorders group

Cross-sectional study on patients with FMD and healthy controls (HC) BEHAVIORAL

Each subject will undergo a set of behavioural, neurophysiological, and Magnetic Resonance Imaging (MRI) tests exploring the motor, exteroceptive and

Also known as: Experiment 1

Functional Motor Disorder group (FMD); Healthy Controls group (HC)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Experiments 1 and 3: Functional Motor Disorders Experiment 2: patients with "organic" motor disorders (weakness due to peripheral neuromuscular disorders, essential tremor, or idiopathic adult-onset dystonia)

You may qualify if:

• Age higher or equal to 18 years
• Clinically definite diagnosis of FMD

You may not qualify if:

• Mini-Mental State Examination score lower or equal to 24
• Physical impairment precluding signing the informed consent for participation
• Certified other neurological and/or psychiatric comorbidities
• Contraindications for 3T MRI
• \- Age higher or equal to 18 years
• Physical impairment precluding signing the informed consent for participation
• Certified neurological and/or psychiatric comorbidities
• Contraindications for 3T MRI
• Experiment 2
• Age higher or equal to 18 years
• Clinically definite diagnosis of "organic" motor disorders: weakness due to peripheral neuromuscular disorders, essential tremor, or idiopathic adult-onset dystonia.
• Score\>2 on the Tremor Research Group Essential Tremor Rating Assessment Scale for patients with essential tremor
• Rest tremors and other neurological signs
• Current or past exposure to tremorgenic drugs
• Mini-Mental State Examination score lower or equal to 24

Sponsors & Collaborators

• Michele Tinazzi, MD, PhD: lead
• IRCCS Ospedale San Raffaele: collaborator
• Azienda Ospedaliera OO.RR. S. Giovanni di Dio e Ruggi D'Aragona: collaborator

Study Sites (3)

Azienda Ospedaliera OO.RR. S. Giovanni di Dio e Ruggi D'Aragona

Salerno, Campania, 84131, Italy

RECRUITING

IRCCS Ospedale San Raffaele

Milan, Lombardy, 20132, Italy

RECRUITING

Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona

Verona, 37131, Italy

RECRUITING

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MeSH Terms

Conditions

Disease; Behavior

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Michele Tinazzi, PhD

  Universita di Verona

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michele Tinazzi, PhD

CONTACT

3480172554; michele.tinazzi@univr.it

Marialuisa Gandolfi, PhD

CONTACT

3491656108; marialuisa.gandolfi@univr.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 18, 2024
• First Posted: March 25, 2024
• Study Start: May 31, 2023
• Primary Completion: May 1, 2025
• Study Completion: May 1, 2025
• Last Updated: March 26, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (3)