Natalizumab and Chronic Inflammation

Assessing the Effect of Natalizumab of Magnetic Resonance Imaging Measures of Blood Brain Barrier Permeability and Myelin Integrity

In this study the investigators will assess the ability of Natalizumab, a medication given to treat multiple sclerosis (MS), to restore blood brain barrier integrity and repair subtle leakages of the blood brain barrier (BBB).

Study Overview

• Status: Terminated
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: Natalizumab 300 MG in 15 ML Injection

Detailed Description

The investigators will image a cohort of persons with relapsing remitting multiple sclerosis (pwRRMS) using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and selective inversion recovery quantitative magnetization transfer imaging (SIR-qMT). pwRRMS will be imaged at baseline and at month-3 and month-12, after starting treatment with natalizumab. Changes in ktrans, a measure of BBB permeability derived from DCE-MRI, and in pool saturation ratio (PSR) a measure of myelin integrity derived from SIR-qMT will be computed to assess the ability of natalizumab to fully restore BBB integrity.

As a corollary aim, the investigators will assess changes in quality of life (QoL) measurements and the relation between those measurements and those derived from the above detailed quantitative MRI methods. QoL will be measured using the Visual Analogue Scale. This questionnaire entails 13 questions regarding the perceived effect of Tysabri, but also level of pain, fatigue, anxiety, depression before and during treatment with natalizumab. The answer to each question is rated on a color-coded bar the range of which is between 0 to 100.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Francesca Bagnato; Phone Number: 615-875-9572; Email: francesca.r.bagnato@vumc.org

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37215
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. multiple sclerosis
2. clinical eligibility to treatment with Natalizumab
3. no previous exposure to Natalizumab treatment

Exclusion Criteria:

1. inability to perform an MRI with contrast
2. inability to undergo a paper-pencil questionnaires and blood work

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Treatment Single Arm; SINGLE ARM: 30 patients with multiple sclerosis treated with Natlizumab infusion given monthly at the dose of 300 mg IV	Drug: Natalizumab 300 MG in 15 ML Injection; Disease modifying agent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of Natalizumab on Magnetic Resonance Imaging Measures of Blood Brain Barrier Permeability: K-trans	To measure changes in k-trans between baseline (pre-treatment) and month-3 and month-12 post-treatment scan	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of Natalizumab on Magnetic Resonance Imaging Measures of Myelin Integrity: Pool Saturation Ratio (PSR)	To measure changes in PSR between baseline (pre-treatment) and month-3 and month-12 post-treatment scan	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of Natalizumab on Questionnaire Derived Measures of Quality of Life	To explore changes in QoL measurements and the relations between these changes and those seen in ktrans and natalizumab serum levels.	12 months

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Collaborators: Biogen
• Investigators: Principal Investigator: Francesca Bagnato, MDPhD, Vanderbilt University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): September 16, 2022
• Primary Completion (Actual): April 5, 2023
• Study Completion (Actual): April 5, 2023

Study Registration Dates

• First Submitted: December 13, 2021
• First Submitted That Met QC Criteria: December 29, 2021
• First Posted (Actual): January 5, 2022

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: multiple sclerosis, MRI, blood brain barrier, myelin
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Physiological Effects of Drugs; Immunologic Factors; Natalizumab
• Other Study ID Numbers: 201600

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Upon reasonable request from qualified investigators the PI will release all data listed below.
• IPD Sharing Time Frame: [per PDBP policy]
• IPD Sharing Access Criteria: [per PDBP policy]
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No