Measuring Active Microglia in Progressive Multiple Sclerosis

NCT02207075 | Completed FDA Drug

• 1 other identifier: 1309014365
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This is pilot study designed to quantifying the innate immune inflammatory burden in a cohort of secondary progressive multiple sclerosis subjects. Innate immunity is recognized as a major cause of tissue injury in central nervous system (CNS) disease. Our hypothesis is that the innate immune response is heightened in SPMS as compared to healthy controls (HC's) and this activity increases over time and correlates with ongoing neuronal loss and disability. The investigators will test this hypothesis by using highly specific molecular imaging techniques, specifically PET, in conjunction with high field MRI. The investigators will utilize the PET radioligand \[11C\]PK11195 which will be used as a marker of activated macrophages/microglia. The investigators will correlate \[11C\]PK11195 uptake with conventional measures of inflammation and neuronal integrity on high-resolution MRI. SPMS subjects will have two baseline \[11C\]PK-11195 PET scans (separated by 24 to 72 hours, test-retest) and subsequent scans at 6, 12 and 24 months. SPMS Subjects will have brain MRI's at baseline, 6, 12 and 24 months. Healthy Controls will have 2 baseline PET scans and one MRI.

Conditions

Secondary Progressive Multiple Sclerosis

Keywords

SPMS; Myelin Water Fraction; activated microglia

Outcome Measures

Primary Outcomes (1)

• Measure the level of baseline and change of whole brain uptake of [11C]PK-11195 at 6, 12 and 24 months in SPMS subjects.

  24 months

Secondary Outcomes (3)

• To correlate the change in T2-hyperintense lesion volume at 6,12 and 24 months of with whole brain uptake of [11C]PK-11195 on PET (at the 6,12 and 24 months) in SPMS subjects.

  24 months

• To correlate the change of conventional MRI measures of neuronal integrity (Gray Matter Fraction, White Matter Fraction, whole brain volume, T1-hypointense lesion volume) at 6,12 and 24 months with whole brain PET uptake of [11C]PK-11195 (at the 6,12 and

  24 months

• To correlate the change in whole brain PET uptake of [11C]PK-11195 (at the 6,12 and 24 months) and level in disability, as measured by a change in EDSS at 6, 12, and 24 months in SPMS subjects.

  24 months

Study Arms (2)

Subjects with SPMS

Secondary progressive MS Subjects either untreated or on consistent treatment for six months prior to enrollment. SPMS subjects will have two baseline \[11C\]PK-11195 PET scans (separated by 24 to 72 hours, test-retest) and subsequent scans at 6, 12 and 24 months. SPMS Subjects will have brain MRI's at baseline, 6, 12 and 24 months.

Drug: [C11]PK-1195 PET scan

Normal Control Subjects

Healthy Controls will have 2 baseline \[C11\]PK-1195 PET scans and 1 MRI.

Drug: [C11]PK-1195 PET scan

Interventions

[C11]PK-1195 PET scan DRUG

PET scan with tracer \[C11\]PK-1195

Normal Control Subjects; Subjects with SPMS

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Approximately 36 subjects (with SPMS and controls) including screen failures will be enrolled regardless of gender

You may qualify if:

• Subjects age 18-80
• Secondary progressive MS subjects either untreated or on consistent treatment for six-months prior to enrollment
• Norman Controls

You may not qualify if:

• Subjects pregnant or woman of child-bearing age not utilizing effective birth control
• Primary progressive MS subjects
• Relapsing remitting MS subjects
• Unstable SPMS subject for which treatment change within the 24 months is likely
• Age-Healthy controls will be excluded if have any of the following medical conditions:
• Any central nervous system disorder
• Any systemic auto-immune disorder
• Pregnant or woman of child-bearing age not utilizing effective birth control
• Subjects will be withdrawn from the study if treatment is changed during the 24-month study

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Genzyme, a Sanofi Company: collaborator

Study Sites (1)

Weill Cornell Medical College

New York, New York, 10021, United States

Location

MeSH Terms

Conditions

Multiple Sclerosis, Chronic Progressive

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Susan Gauthier, DO

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2014
• First Posted: August 1, 2014
• Study Start: July 1, 2014
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2020
• Last Updated: January 18, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)