Conversion DisorderNCT03398070
Neuroimaging Biomarkers of Prognosis in Motor Functional Neurological Disorders
An observational study of Conversion Disorder, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
Functional Neurological Disorder (FND/ Conversion Disorder) is a highly prevalent and disabling neuropsychiatric condition. Motor FND symptoms include Nonepileptic Seizures, Functional Movement Disorders and Functional Weakness. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Conversion Disorder
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Sep 2017to 20 Jan 2023
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Recruitment will occur from patients receiving care in the Massachusetts General Hospital (MGH) Functional Neurological Disorders Clinic
Who may be able to join
- clinically established motor functional neurological disorder, including individuals with functional movement disorders, functional limb weakness and psychogenic nonepileptic seizures
Who cannot join
- active suicidality
- major medical/neurological comorbidities with known central nervous system (CNS) consequences
- active drug use or alcohol dependence
- known history of a primary psychotic disorder
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
Functional Neurological Disorder (FND/ Conversion Disorder) is a highly prevalent and disabling neuropsychiatric condition. Motor FND symptoms include Nonepileptic Seizures, Functional Movement Disorders and Functional Weakness. Clinical research across these motor FND subtypes, including research studies from the candidate's laboratory, suggest that these populations share many clinical and phenotypic similarities that warrant increased research integration. Furthermore, despite the prevalence of motor FND, little is known about the underlying pathophysiology of this condition, which is a prerequisite for the development of biologically informed prognostic and treatment response biomarkers. Across 3 published neurobiologically focused articles, the candidate proposed a framework through which to conceptualize motor FND. It is suggested that motor FND develops in the context of structural and functional alterations in neurocircuits mediating emotion awareness/expression, bodily awareness, viscerosomatic processing and behavioral regulation. The overall goal of this project is to comprehensively investigate structural and functional magnetic resonance imaging (MRI) biomarkers of prognosis across motor FND. Multimodal structural and functional MRI techniques (including voxel-based morphometry, cortical thickness, resting-state functional connectivity and diffusion tensor imaging tractography) will be used to systemically probe brain-prognosis relationships. Novel aspects of this proposal include the study of the full spectrum of motor FND, consistent with a trans-diagnostic approach.
Read the detailed description
Functional Neurological Disorder (FND) (Conversion Disorder) is a poorly understood and prevalent somatoform disorder, making up 16% of outpatient neurology referrals. Patients with motor FND (mFND) are difficult to treat, result in major morbidity, and are costly to the US. An estimated $256 billion is spent annually treating this population. mFND includes Nonepileptic Seizures (NES), Functional Movement Disorders (FMD) and Functional Weakness (FW). An impediment to managing mFND is the lack of a neurobiological understanding for this disorder. The diagnosis of mFND is currently based on qualitative aspects of behaviors, which may be difficult to interpret, and the absence of findings characteristic of other neuropsychiatric disorders on laboratory studies such as electroencephalography (EEG) and magnetic resonance imaging (MRI).
A major step forward would be the identification of neuroimaging biomarkers for mFND. mFND is understudied compared to other disorders, but recent studies point to distributed neurocircuit alterations associated with mFND. This project aims to advance our biological understanding of mFND by investigating neuroimaging biomarkers linked to prognosis. An improved understanding of the pathophysiology of mFND will provide a critical step in elucidating diagnostic, prognostic and treatment response biomarkers.
Aim:
Identify structural and functional biomarkers of prognosis at 6-months in patients with motor functional neurological disorders receiving an updated standard of care.
H1: Favorable mFND prognosis at 6 months post initial evaluation will be predicted by the degree of preserved baseline gray matter in limbic-paralimbic regions, particularly those part of the salience network.
H2: Favorable mFND prognosis at 6 months post initial evaluation will be predicted by the degree of preserved baseline resting-state functional connectivity in limbic/paralimbic areas, particularly those part of the salience network.
H3: Favorable mFND prognosis at 6 months will correlate with the degree of preserved baseline cingulum bundle and cingulum-insular tract integrity.
- Conditions
- Conversion Disorder
- Being tested
- Standard of Care
- Keywords
- Functional Neurological Disorder, Functional Movement Disorder, Psychogenic Nonepileptic Seizures, Functional Limb Weakness
- Medical subject headings
- Conversion Disorder, Psychogenic Nonepileptic Seizures
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standard of CareOther
The standard of care interventions for Functional Neurological Disorders (FND) include:
- delivery of a rule-in diagnosis
- providing educational materials
- referring to physical therapy (PT) and/or occupational therapy (OT) as clinically indicated
- referring to FND-related cognitive behavioral therapy (CBT)
- psychotropic medication management based on standard psychiatric care
| Study group | Role | What they receive |
|---|---|---|
| Motor Functional Neurological Disorder. | The cohort will consist of patients with clinically established motor functional neurological disorder, which includes individuals with functional movement disorders, psychogenic nonepileptic seizures and functional limb weakness.
Patients will be receiving the standard of care within the Massachusetts General Hospital (MGH) Functional Neurological Disorders Clinic.
The updated standard of care that patient's receive in the MGH Functional Neurological Disorders Clinic includes the following:
1. Delivery of a positive "rule-in" diagnosis of functional neurological disorder
2. Individuals are provided with educational materials on functional neurological disorders
3. Referred to physical therapy and/or occupational therapy as clinically indicated
4. FND related cognitive behavioral therapy (CBT) referral when appropriate
5. Psychotropic medication management based on standard psychiatric care Receives: Other: Standard of Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Gray Matter Volume Biomarkers of 6 Month Prognosis as Measured by Voxel Based Morphometry - Within Group Comparison
Correcting for multiple comparisons in structural analyses, baseline structural grey matter volumes in limbic/paralimbic regions (particularly those affiliated with the salience network), would relate to clinical outcome in individuals receiving the standard of care at 6 months. Analyses reported refer to change in either mental health or physical health scores and baseline gray matter volume. The number presented is the peak voxel z-score as also reported in Supplementary Table 4 of the published manuscript.
Z-scores are presented in absolute values (with the lowest value being 0). A higher z-score represents a stronger correlation between a given gray matter volume value (at the peak voxel) and the measure of interest (in case mental health or physical health scores). The entry under "row title" specifies if the association is a "positive" vs a "negative" association.
Measured: baseline and 6 months
Resting State Functional Connectivity Strength Biomarkers of 6 Month Prognosis - Within Group Comparison
Correcting for multiple comparisons in resting state connectivity analyses, baseline functional connectivity strength (t-statistic scores) across limbic/paralimbic regions (particularly those affiliated with the salience network), would relate to clinical outcome in individuals receiving the standard of care at 6 months. Here, we tested if link-step connectivity from primary motor areas or amygdala nuclei related to change in clinical outcome. Specifically, we are providing the t-statistic for the connectivity strength between left centromedial amygdala to right anterior insula.
Functional connectivity strength is based on the correlation of low frequency brain oscillations measured at rest. A large t-statistic value reflects greater connectivity between brain voxels.
Measured: baseline and 6 months
The Integrity of Specific White Matter Tracts (Fractional Anisotropy) as Measured by Diffusion Tensor Imaging (DTI) Tractography Will Relate to 6-month Prognosis
Baseline integrity of the cingulum bundle and cingulate-insular tracts, as measured by fractional anisotropy, would relate to 6 month prognosis in patients with Functional Neurological Disorders (FND) receiving the standard of care.
Outcome was not assessed - no time to analyze data given prior challenges with the pandemic. Unable to report data in any table as the white matter images have not been analyzed.
Measured: baseline and 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2018
- Study start1 Sep 2017
- Primary completion20 Jan 2023
- Study completion20 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Conversion DisorderStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, David Lewis Perez, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03398070
- Sponsor's protocol ID
- 1K23MH111983-01A1
- Status last verified
- Aug 2023
- First submitted
- 15 Dec 2017
- Last updated
- 29 Aug 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Diez I, Ortiz-Teran L, Williams B, Jalilianhasanpour R, Ospina JP, Dickerson BC, Keshavan MS, LaFrance WC Jr, Sepulcre J, Perez DL. Corticolimbic fast-tracking: enhanced multimodal integration in functional neurological disorder. J Neurol Neurosurg Psychiatry. 2019 Aug;90(8):929-938. doi: 10.1136/jnnp-2018-319657. Epub 2019 Mar 8.
PubMed 30850473Perez DL, Williams B, Matin N, Mello J, Dickerson BC, LaFrance WC Jr, Keshavan MS. Anterior hippocampal grey matter predicts mental health outcome in functional neurological disorders: an exploratory pilot study. J Neurol Neurosurg Psychiatry. 2018 Nov;89(11):1221-1224. doi: 10.1136/jnnp-2017-317305. Epub 2018 Jan 11. No abstract available.
PubMed 29326291
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neuroimaging Biomarkers of Prognosis in Motor Functional Neurological Disorders
- ClinicalTrials.gov ID
- NCT03398070
- Acronym / sponsor ID
- 1K23MH111983-01A1
- Conditions
- Conversion Disorder
- Keywords
- Functional Neurological Disorder, Functional Movement Disorder, Psychogenic Nonepileptic Seizures, Functional Limb Weakness
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- 1 Sep 2017 (actual)
- Primary completion
- 20 Jan 2023 (actual)
- Study completion
- 20 Jan 2023 (actual)
- First posted
- 12 Jan 2018 (actual)
- Results
- Posted 29 Aug 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Functional Neurological Disorder (FND/ Conversion Disorder) is a highly prevalent and disabling neuropsychiatric condition. Motor FND symptoms include Nonepileptic Seizures, Functional Movement Disorders and Functional Weakness. Clinical research across these motor FND subtypes, including research studies from the candidate's laboratory, suggest that these populations share many clinical and phenotypic similarities that warrant increased research integration. Furthermore, despite the prevalence of motor FND, little is known about the underlying pathophysiology of this condition, which is a prerequisite for the development of biologically informed prognostic and treatment response biomarkers. Across 3 published neurobiologically focused articles, the candidate proposed a framework through which to conceptualize motor FND. It is suggested that motor FND develops in the context of structural and functional alterations in neurocircuits mediating emotion awareness/expression, bodily awareness, viscerosomatic processing and behavioral regulation. The overall goal of this project is to comprehensively investigate structural and functional magnetic resonance imaging (MRI) biomarkers of prognosis across motor FND. Multimodal structural and functional MRI techniques (including voxel-based morphometry, cortical thickness, resting-state functional connectivity and diffusion tensor imaging tractography) will be used to systemically probe brain-prognosis relationships. Novel aspects of this proposal include the study of the full spectrum of motor FND, consistent with a trans-diagnostic approach.
Detailed description
Functional Neurological Disorder (FND) (Conversion Disorder) is a poorly understood and prevalent somatoform disorder, making up 16% of outpatient neurology referrals. Patients with motor FND (mFND) are difficult to treat, result in major morbidity, and are costly to the US. An estimated $256 billion is spent annually treating this population. mFND includes Nonepileptic Seizures (NES), Functional Movement Disorders (FMD) and Functional Weakness (FW). An impediment to managing mFND is the lack of a neurobiological understanding for this disorder. The diagnosis of mFND is currently based on qualitative aspects of behaviors, which may be difficult to interpret, and the absence of findings characteristic of other neuropsychiatric disorders on laboratory studies such as electroencephalography (EEG) and magnetic resonance imaging (MRI).
A major step forward would be the identification of neuroimaging biomarkers for mFND. mFND is understudied compared to other disorders, but recent studies point to distributed neurocircuit alterations associated with mFND. This project aims to advance our biological understanding of mFND by investigating neuroimaging biomarkers linked to prognosis. An improved understanding of the pathophysiology of mFND will provide a critical step in elucidating diagnostic, prognostic and treatment response biomarkers.
Aim:
Identify structural and functional biomarkers of prognosis at 6-months in patients with motor functional neurological disorders receiving an updated standard of care.
H1: Favorable mFND prognosis at 6 months post initial evaluation will be predicted by the degree of preserved baseline gray matter in limbic-paralimbic regions, particularly those part of the salience network.
H2: Favorable mFND prognosis at 6 months post initial evaluation will be predicted by the degree of preserved baseline resting-state functional connectivity in limbic/paralimbic areas, particularly those part of the salience network.
H3: Favorable mFND prognosis at 6 months will correlate with the degree of preserved baseline cingulum bundle and cingulum-insular tract integrity.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Motor Functional Neurological Disorder. | – | Other: Standard of CareThe cohort will consist of patients with clinically established motor functional neurological disorder, which includes individuals with functional movement disorders, psychogenic nonepileptic seizures and functional limb weakness. Patients will be receiving the standard of care within the Massachusetts General Hospital (MGH) Functional Neurological Disorders Clinic. The updated standard of care that patient's receive in the MGH Functional Neurological Disorders Clinic includes the following: 1. Delivery of a positive "rule-in" diagnosis of functional neurological disorder 2. Individuals are provided with educational materials on functional neurological disorders 3. Referred to physical therapy and/or occupational therapy as clinically indicated 4. FND related cognitive behavioral therapy (CBT) referral when appropriate 5. Psychotropic medication management based on standard psychiatric care |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Recruitment will occur from patients receiving care in the Massachusetts General Hospital (MGH) Functional Neurological Disorders Clinic
Key inclusion criteria (1 listed)
- clinically established motor functional neurological disorder, including individuals with functional movement disorders, functional limb weakness and psychogenic nonepileptic seizures
Key exclusion criteria (4 listed)
- active suicidality
- major medical/neurological comorbidities with known central nervous system (CNS) consequences
- active drug use or alcohol dependence
- known history of a primary psychotic disorder
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 |
|---|---|---|
| Standard of CareThe standard of care interventions for Functional Neurological Disorders (FND) include: 1. delivery of a rule-in diagnosis 2. providing educational materials 3. referring to physical therapy (PT) and/or occupational therapy (OT) as clinically indicated 4. referring to FND-related cognitive behavioral therapy (CBT) 5. psychotropic medication management based on standard psychiatric care | Other | Motor Functional Neurological Disorder. |
Primary outcome
Gray Matter Volume Biomarkers of 6 Month Prognosis as Measured by Voxel Based Morphometry - Within Group Comparison
Time frame: baseline and 6 months
Correcting for multiple comparisons in structural analyses, baseline structural grey matter volumes in limbic/paralimbic regions (particularly those affiliated with the salience network), would relate to clinical outcome in individuals receiving the standard of care at 6 months. Analyses reported refer to change in either mental health or physical health scores and baseline gray matter volume. The number presented is the peak voxel z-score as also reported in Supplementary Table 4 of the published manuscript. Z-scores are presented in absolute values (with the lowest value being 0). A higher z-score represents a stronger correlation between a given gray matter volume value (at the peak voxel) and the measure of interest (in case mental health or physical health scores). The entry under "row title" specifies if the association is a "positive" vs a "negative" association.
Resting State Functional Connectivity Strength Biomarkers of 6 Month Prognosis - Within Group Comparison
Time frame: baseline and 6 months
Correcting for multiple comparisons in resting state connectivity analyses, baseline functional connectivity strength (t-statistic scores) across limbic/paralimbic regions (particularly those affiliated with the salience network), would relate to clinical outcome in individuals receiving the standard of care at 6 months. Here, we tested if link-step connectivity from primary motor areas or amygdala nuclei related to change in clinical outcome. Specifically, we are providing the t-statistic for the connectivity strength between left centromedial amygdala to right anterior insula. Functional connectivity strength is based on the correlation of low frequency brain oscillations measured at rest. A large t-statistic value reflects greater connectivity between brain voxels.
The Integrity of Specific White Matter Tracts (Fractional Anisotropy) as Measured by Diffusion Tensor Imaging (DTI) Tractography Will Relate to 6-month Prognosis
Time frame: baseline and 6 months
Baseline integrity of the cingulum bundle and cingulate-insular tracts, as measured by fractional anisotropy, would relate to 6 month prognosis in patients with Functional Neurological Disorders (FND) receiving the standard of care. Outcome was not assessed - no time to analyze data given prior challenges with the pandemic. Unable to report data in any table as the white matter images have not been analyzed.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 30850473Diez I, Ortiz-Teran L, Williams B, Jalilianhasanpour R, Ospina JP, Dickerson BC, Keshavan MS, LaFrance WC Jr, Sepulcre J, Perez DL. Corticolimbic fast-tracking: enhanced multimodal integration in functional neurological disorder. J Neurol Neurosurg Psychiatry. 2019 Aug;90(8):929-938. doi: 10.1136/jnnp-2018-319657. Epub 2019 Mar 8.
- Results publication: PubMed 29326291Perez DL, Williams B, Matin N, Mello J, Dickerson BC, LaFrance WC Jr, Keshavan MS. Anterior hippocampal grey matter predicts mental health outcome in functional neurological disorders: an exploratory pilot study. J Neurol Neurosurg Psychiatry. 2018 Nov;89(11):1221-1224. doi: 10.1136/jnnp-2017-317305. Epub 2018 Jan 11. No abstract available.
- See Figure 5 for relevant resultsLink provided by the sponsor.
- See Figure 1 for relevant resultsLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Conversion Disorder, run by Massachusetts General Hospital at 1 site in United States.
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 1 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: finished, as of the sponsor's last update on 29 Aug 2023. 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 United States. 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. 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?
Yes. Results are posted in the registry (first posted 29 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Gray Matter Volume Biomarkers of 6 Month Prognosis as Measured by Voxel Based Morphometry - Within Group Comparison (time frame: baseline and 6 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03398070, which also lists 2 linked publications.
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 29 Aug 2023.