Physiologic Volume and Atrophy of Brain and Spinal Cord Measured by Magnetic Resonance Imaging

July 26, 2020 updated by: Dana Horakova

Physiologic Interindividual Variability of Volume and Atrophy in Central Nervous System Structures With Focus on Spinal Cord as Measured by Quantitative Magnetic Resonance Imaging.

Spinal cord (SC) involvement is prevalent in multiple sclerosis (MS) and contributes importantly to disease progression. To be able reliably evaluate spinal cord volume and its changes in MS patients we need to understand variability of these parameters in sex and age matched healthy controls (HC). To date, no generally available data about these parameters in HC are available.

The objective of this study is to investigate age and sex matched HC by MRI to get the basic set of the data representing both cross sectional values and its longitudinal changes.

The present study will also investigate different strategies how to normalize the absolute spinal cord and brain volume data, what is a relationship between spinal cord volume and brain volume and what is the best protocol to be used in a routine clinical practice.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Multiple sclerosis (MS) is a chronic immune-mediated inflammatory and neurodegenerative disease that affects central nervous system. Magnetic resonance imaging (MRI) is the main paraclinical examination used to monitor disease activity and response to treatment. However, there is only limited correlation between the clinical symptoms and findings seen on the conventional MRI - a phenomena called clinical-radiological paradox. Measuring whole and regional brain atrophy provides additional information to MRI and seems to correlate better with clinical course and prognosis. In the last two decades, brain atrophy in MS has been exten sively studied, cut-offs for brain volume loss over time has been established and it is likely that it will become an important outcome measure in both clinical studies and routine practice.

Compared to brain atrophy, spinal cord (SC) atrophy and its relation to MS-related disability has been given less attention. This is partly due to technical challenges such as inhomogeneous magnetic field in this region, small physical dimensions of SC and artefacts caused by motion of the SC within the spinal canal together with the flow of cerebrospinal fluid and periodic motion due to respiratory and cardiac cycles. Moreover, focal spinal cord MS lesions may cause both swelling and shrinking of SC that influence its absolute volume, resulting in problems with interpretation of absolute SC volume in MS. Despite all these challenges, it is possible to identify SC lesions and reliably measure SC volume, but there is no "gold standard" (standardized) software for SC volume measurement and no agreement on the SC level (segments) that is most suitable for SC volume loss measurement.

During 2016 we have developed an in-house semiautomatic pipeline for measurement of cervical spinal cord volume that is a part of Scanview program. The segmentation is performed on T2-weighted images. In the first step, a marker is manually placed in a center of an intervertebral disc C3-4 (sagittal plane). Subsequently a cord straightening (manual rotation of the cord to achieve a perpendicular orientation of spinal cord to dorsal part of C3 vertebral body), that enable to reduce partial volume due to the cord orientation. After this centering and straightening,transformation matrix is saved and all subsequent steps are fully automatized. These steps include: 1. Sub-pixel division, 2. Reversing the contrast of T2-weighted images and smoothing by applying a set of median, Gaussian and edge-enhancing filters and 4. Cubic spline interpolation to find a curve that represents a border of a spinal cord with highest probability. Finally, a sum of mean areas of 21 1-mm slices is calculated (1 center slice fixed at center of a intervertebral disc C3-4 and 2 x 10 slices in cranial and caudal direction. Using this new software we have assessed 1,036 MS patients during 2016 and 2017. The intra- and inter-rater variability of SC volume assessment was done by using the intraclass correlation coefficient (ICC) with a two-way mixed absolute agreement and single-measures design. The analysis confirmed very good consistency (> 98%) of the method. The preliminary results showed a significant correlation between spinal cord volume and different clinical phenotypes.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
102

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Czechia
      • Prague, Czechia, 12000
        • Dpt of Neurology, Charles University and General University Hospital in Prague

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Each participant must provide informed consent in accordance with local regulations
  2. Age 18-60 years.

Exclusion Criteria:

  1. Not able to undergo MRI examination
  2. Not able to be examined 4 times, i.e. M 0, 12, 24, 36 during the next 3 years
  3. Pregnancy at the time of enrollment into the study
  4. Other disease or medical condition that can influence the volume of brain or spinal cord

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: MRI and Neuropsychologic testing

102 healthy controls will be examined by magnetic resonance imaging (MRI) of brain, spinal and thoracic cord at month 0, 12, 24 and 36.

102 healthy controls will be examined by neuropsychological and walking testing designed for patients with multiple sclerosis at month 0, 12, 24 and 36.
Other: Magnetic resonance imaging
At month 0, 12, 24 and 36 participants will be examined by quantitative magnetic resonance imaging of brain, cervical and part of thoracic spine.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Measure Spinal Cord Volume Change at 12 months during 3 years follow-up in Healthy Controls
Time Frame: Baseline, 12, 24, 36 months
Evaluation of Magnetic Resonance Imaging from each visit
Baseline, 12, 24, 36 months
Measure Spinal Cord Atrophy Change at 12 months during 3 years follow-up in Healthy Controls
Time Frame: Baseline, 12, 24, 36 months
Evaluation of Magnetic Resonance Imaging from each visit
Baseline, 12, 24, 36 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Measure Whole Brain Volume and Atrophy at 12 months during 3 years follow-up in Healthy Controls
Time Frame: Baseline, 12, 24, 36 months
Evaluation of Magnetic Resonance Imaging from each visit
Baseline, 12, 24, 36 months
Measure Regional Brain Volumes and Atrophies at 12 months during 3 years follow-up in Healthy Controls
Time Frame: Baseline, 12, 24, 36 months
Evaluation of Magnetic Resonance Imaging from each visit
Baseline, 12, 24, 36 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Dana Horakova

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Dana Horakova, MD, PhD, Dpt of Neurology, Charles University and General University Hospital in Prague

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 15, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 14, 2018

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 17, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 12, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 15, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 29, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 26, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • KHL 182/2017

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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