Psychosocial, Behavioral, and Radiologic Changes Following Radiosurgery for Benign Neurologic Disease

• ClinicalTrials.gov Identifier: NCT04688554
• Recruitment Status: Recruiting
• First Posted: December 30, 2020
• Last Update Posted: December 30, 2020
• Sponsor: Vanderbilt University Medical Center
• Collaborator: Varian Medical Systems
• Information provided by (Responsible Party): Mohamed Khattab, Vanderbilt University Medical Center

Study Description

Brief Summary:

A number of studies from the literature suggest important behavioral, psychosocial, or radiologic changes occur following significant neurologic events or interventions such as stroke, neurosurgery, medications, radiation, systemic therapy, or injury. The purpose of this study is to describe these changes with advanced neurologic imaging and targeted neurologic and neuropsychiatric assessments. This is a non-interventional observational study of minimal risk to participants as there is no medical intervention. The results of this study will be used to inform patients, scientists, and society in the development of future treatments.

Condition or disease	Intervention/treatment
Obsessive-Compulsive Disorder; Pain, Intractable; Depression	Diagnostic Test: fMRI and DTI; Behavioral: Behavioral questionnaires; Behavioral: Disease-Specific Patient-Reported Outcomes; Behavioral: Behavioral tests

Detailed Description:

Functional magnetic resonance imaging (fMRI) and diffusion tensor tractography (DTI) have rapidly expanded since its emergence two decades ago. fMRI is well established as the single most powerful method for detecting changes in neural activity in vivo, albeit indirectly by detection of changes in blood oxygenation level dependent (BOLD) signals that reflect hemodynamic changes subsequent to neural activity. A conventional fMRI experiment involves the comparison of two or more brain states followed by statistical tests to identify which brain regions were involved in a particular task. The identification of patterns of highly correlated low-frequency MRI signals in the resting brain provides a powerful approach to delineate and describe neural circuits, and an unprecedented ability to assess the manner in which distributed regions work together to achieve specific functions. Since the first reports of temporal correlations in BOLD baseline signals, several distinct cortical long-range networks have been identified and characterized in the resting state, including a default mode network. Moreover, observations of altered resting state connectivity in several disorders and as a function of behavior or cognitive skills suggest these correlations reflect an important level of brain organization and may play a fundamental role in the execution and maintenance of various brain functions. DTI is also an exceedingly important imaging modality that has elucidated the neural connectivity inherent between various cortical and subcortical structures. DTI is routinely used and has enhanced our understanding of functional connections between various parts of the brain. Prior to interventions, DTI is commonly obtained, so that interventionists can avoid critical circuitry. There is suggestion that both fMRI and DTI imaging is influenced by organic or interventional variables, however this is understudied. The neuroscientists and clinicians would greatly value information that would expand our working knowledge of the basic neural substrates and functional neural changes that occur in patients organically or after interventions. A non-invasive, non-interventional, observational study is needed to show the changes that happen to patients organically or in standard of care settings. A greater working understanding of the neural connectivity and changes that happen in the brain is of great future benefit to patients, science, and society as well as future therapeutic development such as post-stroke care, rehabilitation, post-traumatic brain injury, or post-treatment care in the brain that has previously been influenced by intervention or disease.

Study Design

• Study Type: Observational
• Estimated Enrollment: 50 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Psychosocial, Behavioral, and Radiologic Changes Following Neurologic Events or Interventions: A Prospective, Non-Interventional, Observational Study
• Actual Study Start Date: August 25, 2020
• Estimated Primary Completion Date: August 25, 2025
• Estimated Study Completion Date: August 25, 2025

Groups and Cohorts

Group/Cohort	Intervention/treatment
Refractory Obsessive Compulsive Disorder; fMRI, DTI, behavioral, psychological, and disease-specific changes following radiosugical capsulotomy	Diagnostic Test: fMRI and DTI; Neurologic imaging correlates; Behavioral: Behavioral questionnaires; RAND 36-item Quality of Life survey, Mini Mental Status Exam, MOCA Cognitive Exam; Behavioral: Disease-Specific Patient-Reported Outcomes; Y-BOCS Survey, QUEST, PDQ39, PHQ2 Depression Screening, PHQ9 Depression Inventory, Beck's Depression Inventory, PROMIS Pain Intensity Short Form 3, McGill Pain Scale, Visual Analog pain scale, FTM (Tremor Scale); Behavioral: Behavioral tests; Behavioral tests may include one or more of the following procedures: Upper extremity testing, Perdue Peg Board testing, Hand tactile detection and discrimination test, Temperature and pain threshold testing, Lower extremity Testing, Myomotion Inertial Motion Testing.
Refractory Pain; fMRI, DTI, behavioral, psychological, and disease-specific changes following radiosugical cingulotomy	Diagnostic Test: fMRI and DTI; Neurologic imaging correlates; Behavioral: Behavioral questionnaires; RAND 36-item Quality of Life survey, Mini Mental Status Exam, MOCA Cognitive Exam; Behavioral: Disease-Specific Patient-Reported Outcomes; Y-BOCS Survey, QUEST, PDQ39, PHQ2 Depression Screening, PHQ9 Depression Inventory, Beck's Depression Inventory, PROMIS Pain Intensity Short Form 3, McGill Pain Scale, Visual Analog pain scale, FTM (Tremor Scale); Behavioral: Behavioral tests; Behavioral tests may include one or more of the following procedures: Upper extremity testing, Perdue Peg Board testing, Hand tactile detection and discrimination test, Temperature and pain threshold testing, Lower extremity Testing, Myomotion Inertial Motion Testing.
Refractory Tremor; fMRI, DTI, behavioral, psychological, and disease-specific changes following radiosugical thalamotomy	Diagnostic Test: fMRI and DTI; Neurologic imaging correlates; Behavioral: Behavioral questionnaires; RAND 36-item Quality of Life survey, Mini Mental Status Exam, MOCA Cognitive Exam; Behavioral: Disease-Specific Patient-Reported Outcomes; Y-BOCS Survey, QUEST, PDQ39, PHQ2 Depression Screening, PHQ9 Depression Inventory, Beck's Depression Inventory, PROMIS Pain Intensity Short Form 3, McGill Pain Scale, Visual Analog pain scale, FTM (Tremor Scale); Behavioral: Behavioral tests; Behavioral tests may include one or more of the following procedures: Upper extremity testing, Perdue Peg Board testing, Hand tactile detection and discrimination test, Temperature and pain threshold testing, Lower extremity Testing, Myomotion Inertial Motion Testing.
Refractory Depression; fMRI, DTI, behavioral, psychological, and disease-specific changes following radiosugical cingulotomy	Diagnostic Test: fMRI and DTI; Neurologic imaging correlates; Behavioral: Behavioral questionnaires; RAND 36-item Quality of Life survey, Mini Mental Status Exam, MOCA Cognitive Exam; Behavioral: Disease-Specific Patient-Reported Outcomes; Y-BOCS Survey, QUEST, PDQ39, PHQ2 Depression Screening, PHQ9 Depression Inventory, Beck's Depression Inventory, PROMIS Pain Intensity Short Form 3, McGill Pain Scale, Visual Analog pain scale, FTM (Tremor Scale); Behavioral: Behavioral tests; Behavioral tests may include one or more of the following procedures: Upper extremity testing, Perdue Peg Board testing, Hand tactile detection and discrimination test, Temperature and pain threshold testing, Lower extremity Testing, Myomotion Inertial Motion Testing.

Outcome Measures

Primary Outcome Measures :

1. Describe changes in Obsessive Compulsive Disorder disease burden after stereotactic radiosurgery. [ Time Frame: Every 3 months for 1 year or through study completion ]
   Yale-Brown Obsessive Compulsive Scale questionnaire
2. Describe changes in Depression disease burden after stereotactic radiosurgery. [ Time Frame: Every 3 months for 1 year or through study completion ]
   Beck's Depression inventory
3. Describe changes in Pain disease burden after stereotactic radiosurgery. [ Time Frame: Every 3 months for 1 year or through study completion ]
   McGill Pain Scale

Secondary Outcome Measures :

1. Describe changes in cognition after stereotactic radiosurgery. [ Time Frame: Every 3 months for 1 year or through study completion ]
   Montreal Cognitive Assessment
2. Describe changes in radiologic parameters after stereotactic radiosurgery. [ Time Frame: Every 6 months for 1 year or through study completion ]
   Brain MRI

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

VUMC adult patients with neurologic disease or patients with neurologic interventions such as neurosurgical procedures or radiation therapy. Men and women of any ethnicity, race or socioeconomic status who meet inclusion criteria will be offered enrollment into the study. Patient will be greater than 18 years of age and meet inclusion and exclusion criteria. Patients eligible for this study will include patients with neurologic events, including but not limited to stroke, depression, infections, psychiatric disease. Intervention is not part of this study, however, patients receiving neurologic interventions, such as neurosurgical procedures or radiation therapy, would be eligible.

Criteria

Inclusion Criteria:

• Age ≥ 18 years old and willing and able to sign a written informed consent.
• Eligible for Brain MRI
• History of neurologic event or intervention OR future planned neurologic intervention

Exclusion Criteria:

• Contraindications to MRI of the brain
• Patient declining participation in study

Contacts and Locations

Contacts

Contact: Mohamed H Khattab, MD; (615) 322-2555; mohamed.khattab@vumc.org

Contact: Alexander D Sherry, MD; (615) 322-2555; alexander.d.sherry@vanderbilt.edu

Locations

United States, Tennessee

Vanderbilt University Medical Center; Recruiting

Nashville, Tennessee, United States, 37232-5671

Contact: Mohamed H Khattab, MD 615-322-2555 mohamed.khattab@vumc.org

Principal Investigator: Mohamed H Khattab, MD

Sub-Investigator: Anthony J Cmelak, MD

Sub-Investigator: William Petrie, MD

Sub-Investigator: Jonathan E Becker, DO

Sub-Investigator: Alexander D Sherry, MD

Sponsors and Collaborators

Vanderbilt University Medical Center

Varian Medical Systems

Investigators

• Principal Investigator: Mohamed H Khattab, MD; Vanderbilt University Medical Center
• Study Chair: Anthony J Cmelak, MD; Vanderbilt University Medical Center

  Study Documents (Full-Text)

Documents provided by Mohamed Khattab, Vanderbilt University Medical Center:

Study Protocol and Statistical Analysis Plan  [PDF] May 18, 2020

More Information

• Responsible Party: Mohamed Khattab, Chief Resident, Department of Radiation Oncology, Vanderbilt University Medical Center
• ClinicalTrials.gov Identifier: NCT04688554
• Other Study ID Numbers: 200209
• First Posted: December 30, 2020
• Last Update Posted: December 30, 2020
• Last Verified: December 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Research data will be shared upon reasonable request to the principal investigator.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)
• Time Frame: Data will become available after the publication of the study results.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Mohamed Khattab, Vanderbilt University Medical Center:

Stereotactic Radiosurgery; Cingulotomy; Capsulotomy

Additional relevant MeSH terms:

Pain, Intractable; Obsessive-Compulsive Disorder; Mental Disorders; Anxiety Disorders; Pain; Neurologic Manifestations