Tracking Peripheral Immune Cell Infiltration of the Brain in Central Inflammatory Disorders Using [Zr-89]Oxinate-4-labeled Leukocytes.

This study will use brain Positron Emission Tomography/ Magnetic Resonance Imaging (PET/MRI) and an investigational radioactive drug called [Zr-89]oxine to track the location of white blood cells (also called leukocytes) in the body. PET/MRI will be used to visualize labeled white blood cells and determine if they enter the central nervous system in conditions associated with brain inflammation (also called neuroinflammation). By better understanding the role of neuroinflammation in fibromyalgia, chronic fatigue syndrome, and multiple sclerosis, the investigator hopes to be able to better diagnose and treat patients in the future.

Study Overview

• Status: Recruiting
• Conditions: Multiple Sclerosis; Healthy; Fibromyalgia; Chronic Fatigue Syndrome
• Intervention / Treatment: Drug: [Zr-89]Oxine-labeled leukocytes PET/MRI

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Evan Hudson, BS; Phone Number: 205-934-6499; Email: evanhudson@uabmc.edu
• Study Contact Backup: Name: Jonathan McConathy, MD, PhD; Phone Number: 205-996-7115; Email: jmcconathy@uabmc.edu

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Recruiting
      • UAB
      • Contact: Evan Hudson, BS; Phone Number: 205-934-6499; Email: evanhudson@uabmc.edu
      • Principal Investigator: Jonathan McConathy, MD,PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1.18 to 65 years of age 2.Healthy volunteer OR

• Clinical diagnosis of Multiple Sclerosis (MS) OR
• Meets 2016 American College of Rheumatology (ACR) case definition criteria for fibromyalgia OR
• Meets 1994 Fukuda case definition criteria for Chronic Fatigue Syndrome

Exclusion Criteria:

1. Contraindication to MRI
2. Pregnancy
3. Lactation
4. Individuals who are unable to participate in the imaging portion due to severity of their medical condition
5. Chronic infectious disease (e.g. HIV, HCV)
6. Viral or bacterial illness requiring medical attention and/or antibiotics within 1 month of study participation
7. Diagnosis of cancer, including leukemia
8. Blood or blood clotting disorder
9. Except for individuals with MS, a diagnosis of autoimmune disease is exclusionary
10. Positive urine pregnancy test day of procedure or a serum pregnancy test within 48 hours prior to the administration of Zirconium-89 Oxinate-4-labeled leukocytes
11. Currently enrolled in a clinical trial utilizing experimental therapies
12. Contraindication to gadolinium based contrast agents

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healthy Controls	Drug: [Zr-89]Oxine-labeled leukocytes PET/MRI; All study participants will undergo an investigational imaging study using autologous [Zr-89]-labeled leukocytes and brain PET/MRI. Participants will undergo a venous blood draw, and the leukocytes in the blood sample will be isolated for labeling using [Zr-89]oxine. The labeled leukocytes (7.4- 18.5 megabecquerel (MBq), 200-500 uCi) will be re-injected into the participant followed by brain PET/MRI at 24-48 hours after injection. Participants will be asked to have a second brain imaging study 3-6 days after this injection, but this second imaging study is optional.
Experimental: Fibromyalgia	Drug: [Zr-89]Oxine-labeled leukocytes PET/MRI; All study participants will undergo an investigational imaging study using autologous [Zr-89]-labeled leukocytes and brain PET/MRI. Participants will undergo a venous blood draw, and the leukocytes in the blood sample will be isolated for labeling using [Zr-89]oxine. The labeled leukocytes (7.4- 18.5 megabecquerel (MBq), 200-500 uCi) will be re-injected into the participant followed by brain PET/MRI at 24-48 hours after injection. Participants will be asked to have a second brain imaging study 3-6 days after this injection, but this second imaging study is optional.
Experimental: Chronic Fatigue Syndrome	Drug: [Zr-89]Oxine-labeled leukocytes PET/MRI; All study participants will undergo an investigational imaging study using autologous [Zr-89]-labeled leukocytes and brain PET/MRI. Participants will undergo a venous blood draw, and the leukocytes in the blood sample will be isolated for labeling using [Zr-89]oxine. The labeled leukocytes (7.4- 18.5 megabecquerel (MBq), 200-500 uCi) will be re-injected into the participant followed by brain PET/MRI at 24-48 hours after injection. Participants will be asked to have a second brain imaging study 3-6 days after this injection, but this second imaging study is optional.
Experimental: Multiple Sclerosis	Drug: [Zr-89]Oxine-labeled leukocytes PET/MRI; All study participants will undergo an investigational imaging study using autologous [Zr-89]-labeled leukocytes and brain PET/MRI. Participants will undergo a venous blood draw, and the leukocytes in the blood sample will be isolated for labeling using [Zr-89]oxine. The labeled leukocytes (7.4- 18.5 megabecquerel (MBq), 200-500 uCi) will be re-injected into the participant followed by brain PET/MRI at 24-48 hours after injection. Participants will be asked to have a second brain imaging study 3-6 days after this injection, but this second imaging study is optional.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Regional brain distribution of radiolabeled white blood cells	Descriptive statistics (means and standard deviations) of standardized uptake values (SUVs) will be presented for the patient groups and healthy controls in the following regions: whole brain, gray matter, white matter, atlas-based regions of interest, and lesions (MS patients only). Normality of the SUV distribution will be tested using Shapiro-Wilk tests, and the data will be transformed to normal distribution if necessary.	3 years

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Investigators: Principal Investigator: Jonathan McConathy, MD,PhD, University of Alabama at Birmingham

Study record dates

Study Major Dates

• Study Start (Actual): October 5, 2021
• Primary Completion (Estimated): October 5, 2024
• Study Completion (Estimated): October 5, 2025

Study Registration Dates

• First Submitted: January 14, 2019
• First Submitted That Met QC Criteria: January 14, 2019
• First Posted (Actual): January 17, 2019

Study Record Updates

• Last Update Posted (Estimated): February 14, 2024
• Last Update Submitted That Met QC Criteria: February 13, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Muscular Diseases; Neuromuscular Diseases; Encephalomyelitis; Neuroinflammatory Diseases; Multiple Sclerosis; Fibromyalgia; Fatigue Syndrome, Chronic
• Other Study ID Numbers: R18-179

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.: Yes