Clinical trial NCT03218111: Glymphatic Kinetics In Healthy Adult Volunteers
Official title: Evaluation Of Brain Glymphatic Kinetics Following Intrathecal Administration Of Gadolinium In Healthy Adult Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy
Keywords: Glymphatic network
healthy
central nervous system
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
Collaborators: name: Biogen
First posted: 2017-07-14
Enrollment: 19
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Drug distribution over time
timeFrame: 6 time-points over 12 hours
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
Study officials:
affiliation: Weill Medical College of Cornell University
name: J. Levi Chazen, MD
role: PRINCIPAL_INVESTIGATOR
References: