Brain Peripheral Benzodiazepine Receptors in Patients With Multiple Sclerosis

NCT00432900 | Completed Phase 1

• 2 other identifiers: 07009207-N-0092
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

This study will use positron emission tomography (PET) to measure a brain protein called peripheral benzodiazepine receptor (PBR) in patients with multiple sclerosis. PBR is created during the inflammation process, and brain inflammation is a key feature of multiple sclerosis (MS). PBR usually affects one type of brain cell, but it can also cause damage to surrounding areas of the brain in patients with MS. PET studies of PBRs and brain inflammation may help elucidate the role of these brain cells in patients with MS. Healthy normal volunteers and patients with MS between 18 and 70 years of age may be eligible for this study. Patients with MS must have had onset of disease between 18 and 40 years of age. Patients with MS undergo the following procedures: Visit 1: Medical history, physical examination, blood tests and magnetic resonance imaging (MRI). Visit 2: Blood tests and PET scan. Visits 3 and 4: MRI and physical examination. Visit 5: PET scan and blood tests. Visit 6: MRI and physical examination. Healthy volunteers undergo the following: Visit 1: Medical history, physical examination, blood tests. Visits 2 and 3: PET and blood tests. Magnetic Resonance Imaging MRI uses a magnetic field and radio waves to produce images of body tissues and organs. For this procedure, the subject lies on a table that can slide in and out of the scanner (a metal cylinder), wearing earplugs to muffle loud knocking noises that occur during the scanning process. The procedure lasts about 90 minutes; the patient is asked to lie still for up to 25 minutes at a time. The subject can communicate with the MRI staff at all times during the scan. During part of the scan a contrast agent is administered through a catheter (plastic tube) placed in an arm vein to enhance the images. Positron Emission Tomography (PET) The PET scan gives information on brain and body chemistry and function. The subject lies on a bed that slides in and out of the doughnut-shaped scanner. A catheter is placed in a vein in the arm and another is placed in an artery in the wrist or elbow area. The catheter in the arm is used for injecting a radioactive material that the scanner detects, and the other is used to collect blood samples. A custom-molded plastic mask is used to support the head and prevent it from moving during the procedure. The subject may be asked to perform various tasks during the PET scan or to lie quietly. The scan lasts about 2.5 hours.

Conditions

Multiple Sclerosis

Keywords

Inflammation; Neuroimmunology; Multiple Sclerosis; MS; Healthy Volunteer; HV

Outcome Measures

Primary Outcomes (2)

• Correspondence between increased PBR expression measured by [11C]PBR28 PET and gadolinium-enhancing lesions on MRI.

  At time of dosing

• Correspondence between increased PBR expression and previously and/or persistently gadolinium-enhancing lesions on MRI.

  At time of dosing

Secondary Outcomes (2)

• Correspondence between PBR expression and other MRI defined pathology including T2-weighted hyperintense and T1-weighted hypointense lesions.

  Follow-up (~Month 4)

• Correspondence between PBR expression and normal appearing white and gray matter on MRI.

  Follow-up (~Month 4)

Study Arms (2)

Healthy Volunteer

ACTIVE COMPARATOR

Healthy Volunteers

Radiation: [(11)C]PBR28

Patient

EXPERIMENTAL

Multiple Sclerosis Patients

Radiation: [(11)C]PBR28

Interventions

[(11)C]PBR28 RADIATION

PET Ligand

Healthy Volunteer; Patient

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ages between 18 and 70, inclusive.
• Diagnosis of definite MS according to published criteria.
• The presence of at least one gadolinium-enhancing lesion on the screening brain magnetic resonance image (MRI), and T2 lesion load volume greater than 5 cc.
• Subjects must be able to provide written, informed consent prior to any testing under this protocol, including screening and baseline investigations that are not considered part of routine patient care.

You may not qualify if:

• Prior participation in other research protocols or clinical care in the last year such that radiation exposure would exceed the annual guidelines.
• Homozyous for the low- affinity binding form of TSPO by TSPO genotype analysis ( Ala147Thr polymorphism in rs6971 SNP in exon 4 of the TSPO gene).
• Pregnancy and breast-feeding.
• Presence of ferromagnetic metal in the body or heart pacemaker.
• ECG with clinically significant abnormalities.
• Positive HIV test.
• Positive pregnancy test.
• Concurrent medical conditions including hepatic cirrhosis, end-stage renal disease or any acute and severe decompensation of disease that in the opinion of the investigator would compromise the safety of the patient.
• Subjects with cognitive impairment who are unable to provide written, informed consent.
• Subjects who have received immunomodulatory/disease-modifying therapy, including investigational MS therapy, within 12 weeks prior to PET imaging or who have received corticosteroids within 6 weeks prior to PET imaging.
• All subjects must be healthy and aged 18-70 years.
• Homozyous for the low- affinity binding form of TSPO by TSPO genotype analysis ( Ala147Thr polymorphism in rs6971 SNP in exon 4 of the TSPO gene).
• Current psychiatric illness, substance abuse or severe systemic disease based on history and physical exam.
• ECG with clinically significant abnormalities. Any existing physical exam and ECG within one year will be reviewed and if none already exists in the chart, these will be obtained and reviewed.
• Laboratory tests with clinically significant abnormalities.

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, McFarland HF, Paty DW, Polman CH, Reingold SC, Sandberg-Wollheim M, Sibley W, Thompson A, van den Noort S, Weinshenker BY, Wolinsky JS. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001 Jul;50(1):121-7. doi: 10.1002/ana.1032.

  PMID: 11456302 BACKGROUND

• Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG. Multiple sclerosis. N Engl J Med. 2000 Sep 28;343(13):938-52. doi: 10.1056/NEJM200009283431307. No abstract available.

  PMID: 11006371 BACKGROUND

• Cotton F, Weiner HL, Jolesz FA, Guttmann CR. MRI contrast uptake in new lesions in relapsing-remitting MS followed at weekly intervals. Neurology. 2003 Feb 25;60(4):640-6. doi: 10.1212/01.wnl.0000046587.83503.1e.

  PMID: 12601106 BACKGROUND

MeSH Terms

Conditions

Multiple Sclerosis; Inflammation

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Steven Jacobson, Ph.D.

  National Institute of Neurological Disorders and Stroke (NINDS)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH

Study Record Dates

• First Submitted: February 7, 2007
• First Posted: February 8, 2007
• Study Start: February 5, 2007
• Primary Completion: May 23, 2013
• Study Completion: May 29, 2013
• Last Updated: December 12, 2019

Record last verified: 2014-04-22

Locations

US (1)