Glymphatic Kinetics In Healthy Adult Volunteers

Evaluation Of Brain Glymphatic Kinetics Following Intrathecal Administration Of Gadolinium In Healthy Adult Volunteers

This study is being done in order to see how gadolinium-based MRI contrast (Magnevist) travels through the central nervous system (CNS) when injected through the spinal column, and to compare differences between two age groups (age 20-50, and 51-80). This will allow investigators to evaluate how much contrast has crossed into the tissue surrounding the brain. Such information will help investigators determine whether this kind of contrast can be used to model how other drugs might travel through the CNS and evaluate its use as an illustrative imaging marker that mirrors the glymphatic system.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Other: MR Imaging; Other: CT-guidance

Detailed Description

This is a prospective, longitudinal study of MR imaging of intrathecally delivered gadolinium contrast (Magnevist, Gd-DTPA) in healthy adult male and female subjects. Subjects will be divided into two groups (20-50 years old and 51-80 years old) both of which will receive intrathecal injection of the drug Magnevist (Gd-DTPA), followed by serial MR imaging over the course of 10-12 hours. The purpose of the study is determine the transport kinetics of Central Nervous System (CNS) exposure to gadolinium contrast injected into the lumbar intrathecal space (lower back) and evaluate changes with age. This will allow investigators to evaluate the brain parenchymal penetration of gadolinium as an illustrative imaging marker that mirrors the glymphatic system. Investigators hypothesize the exposure and penetration patterns of the neuraxis to neurotherapeutic drugs can be modeled using gadolinium intrathecal contrast administered in the lumbar intrathecal space.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Weill Cornell Medical College

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Deemed healthy and able to undergo MR imaging by the Site Investigator, based on screening assessments:

   medical history, physical examination, vital signs, and clinical laboratory values

2. Age 20-80
3. Willing to undergo multiple imaging sessions
4. Normal screening MRI to exclude subjects with a mass (e.g., disk herniation), congenital malformation (e.g., Chiari malformation), or an abnormal curvature of the spine that could alter CSF flow.
5. If female of childbearing age: negative pregnancy test
6. Normal Basic metabolic Panel and CBC (Platelet count > 150,000; Hb >8)
7. Willing to undergo LP procedure. -

Exclusion Criteria:

1. Kyphosis
2. Claustrophobia
3. Chronic cough
4. Active infection with fever (>101.5), to limit risk of meningitis. Infections could include pneumonia, pharyngitis, skin infection, UTI, etc.
5. History of CNS tumor or anomaly
6. History of radiation therapy to the CNS
7. History of hydrocephalus
8. Abnormality on MRI that could impede CSF flow (i.e., extruded disk)
9. Laboratory finding of prolonged coagulation times
10. Pregnant/nursing
11. Prior spine or brain surgery or trauma
12. Inability to lay still and supine
13. Recent lumbar puncture within 1 month of planned LP.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: Healthy Normal Subjects; Healthy normal subjects 20-80 years old. All subjects will undergo the same procedures: intrathecal injection, using CT-guidance, with an MRI contrast. After injection subjects will undergo six sessions of MR imaging over a 10-12 hour period	Other: MR Imaging; All subjects will undergo six sessions of MR imaging over a 10-12 hour period; Other: CT-guidance; All subjects will be injected, intrathecally using CT-guidance, with an MRI contrast.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Drug distribution over time	The drug distribution of gadolinium contrast throughout the Central Nervous System over time (12 hours)	6 time-points over 12 hours

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Collaborators: Biogen
• Investigators: Principal Investigator: J. Levi Chazen, MD, Weill Medical College of Cornell University

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 6, 2017
• Primary Completion (ACTUAL): February 6, 2018
• Study Completion (ACTUAL): February 8, 2018

Study Registration Dates

• First Submitted: July 7, 2017
• First Submitted That Met QC Criteria: July 11, 2017
• First Posted (ACTUAL): July 14, 2017

Study Record Updates

• Last Update Posted (ACTUAL): February 12, 2018
• Last Update Submitted That Met QC Criteria: February 9, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: healthy; central nervous system; Glymphatic network
• Other Study ID Numbers: 1609017536

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No Current Plan

Drug and device information, study documents

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