A Study of FolateScan in Patients With Knee Osteoarthritis

Study of 99mTc-EC20 Imaging (FolateScan) in Participants With Knee Osteoarthritis

The purpose of this study is to evaluate 99mTc - EC20 imaging (FolateScan), a Nuclear Medicine imaging technology that enables localization of activated macrophages in the joints of participants with knee osteoarthritis (OA). Twenty five participants with symptomatic unilateral or bilateral knee OA will undergo a one-time evaluation of the knee as follows: knee radiography, FolateScan of the knees and whole body, musculoskeletal exam, questionnaires, sampling of blood, urine and synovial fluid for analysis of inflammatory markers. Data analysis will be cross-sectional and include a comparison of the location and intensity of EC20 uptake with the following: radiographic knee OA severity, clinical measures of disease severity, cytokine expression, and synovial fluid cell count.

Study Overview

• Status: Completed
• Conditions: Knee Osteoarthritis
• Intervention / Treatment: Drug: 99mTc-EC20

Detailed Description

Each study day will on average last one day per individual and each individual will be followed for development of an Adverse Event for 7 days

• Study Type: Observational
• Enrollment (Actual): 25

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Males and females over the age of 18 years with at least one symptomatic knee with evidence of osteoarthritis on radiograph.

Description

Inclusion Criteria: Unilateral or bilateral knee OA; Kellgren Lawrence grade 1-4; Knee pain on most days of any one-month in the last year in at least one knee; Age > 18 years old.

Exclusion Criteria: Arthroscopic knee surgery within the previous 12 months; Intra-articular injection or systemic (oral, IV, IM) steroid within previous 6 months; Any knee replacement; Current enrollment in, or discontinued within the last 30 days from, a clinical trial involving an off-label use of an investigational drug or device (other than the study drug used in this study); Pregnancy; Positive serum beta HCG within 48 hours prior to 99mTc-EC20 administration and/or lactation; Rheumatoid arthritis or other inflammatory arthropathy; Avascular necrosis; Periarticular fracture; Current anticoagulant therapy; Current immune modulator therapy, or any such therapy within 4 weeks of study procedures; Inability to discontinue use of NSAIDS within 3 days of study procedures (low dose aspirin of up to 325 mg per day is permitted); Must be able to stop Folic Acid containing vitamins 24 hrs before study; Paget's disease; Villonodular synovitis; Joint infection; Ochronosis; Neuropathic arthropathy; Acromegaly; Hemochromatosis; Wilson's disease; Osteochondromatosis; Personnel directly affiliated with this study or their immediate family members; Concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Knee Osteoarthritis; Unilateral or bilateral knee osteoarthritis on radiograph associated with knee pain on most days of any one-month in the last year in at least one knee. Study participants underwent a one-time evaluation by FolateScan which entailed a single intravenous injection of 99mTc-EC20 (total volume of 1.0 to 2.0 ml administered over a period of 30 seconds with radioactive dose between 20 and 25 mCi).

Drug: 99mTc-EC20; Study participants underwent a one-time evaluation by FolateScan which entailed a single intravenous injection of 99mTc-EC20 (total volume of 1.0 to 2.0 ml administered over a period of 30 seconds with radioactive dose between 20 and 25 mCi). A total of three imaging scans were acquired: an early phase (at ~1 minute) SPECT/CT of both knees; a late phase (at ~60 minutes) SPECT/CT image of both knees; and a late phase (at ~80 minutes) planar image of the whole body was performed (anterior-posterior, and postero-anterior).; Other Names: (FolateScan Imaging Drug)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of knee uptake of 99mTc-EC20	These data will be collected at a single timepoint (baseline) only and participants will not be further followed.	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intensity and location of uptake of 99mTc-EC20	These data will be collected at a single timepoint (baseline) only and participants will not be further followed.	Baseline
Correlation of knee symptoms and knee uptake of 99mTc-EC20	This analysis will be performed from data collected at a single timepoint (baseline) only and participants will not be further followed.	Baseline
Correlation of 99mTc-EC20 uptake and biomarkers	This analysis will be performed from data collected at a single timepoint (baseline) only and participants will not be further followed.	Baseline
Correlation of knee radiographic OA and knee uptake of 99mTc-EC20	This analysis will be performed from data collected at a single timepoint (baseline) only and participants will not be further followed.	Baseline

Collaborators and Investigators

• Sponsor: Virginia Kraus
• Collaborators: Eli Lilly and Company; Endocyte
• Investigators: Principal Investigator: Virginia B Kraus, MD, PhD, Duke University

Publications and helpful links

General Publications

• Matteson EL, Lowe VJ, Prendergast FG, Crowson CS, Moder KG, Morgenstern DE, Messmann RA, Low PS. Assessment of disease activity in rheumatoid arthritis using a novel folate targeted radiopharmaceutical Folatescan. Clin Exp Rheumatol. 2009 Mar-Apr;27(2):253-9.
• Haraden CA, Huebner JL, Hsueh MF, Li YJ, Kraus VB. Synovial fluid biomarkers associated with osteoarthritis severity reflect macrophage and neutrophil related inflammation. Arthritis Res Ther. 2019 Jun 13;21(1):146. doi: 10.1186/s13075-019-1923-x.
• Kraus VB, McDaniel G, Huebner JL, Stabler TV, Pieper CF, Shipes SW, Petry NA, Low PS, Shen J, McNearney TA, Mitchell P. Direct in vivo evidence of activated macrophages in human osteoarthritis. Osteoarthritis Cartilage. 2016 Sep;24(9):1613-21. doi: 10.1016/j.joca.2016.04.010. Epub 2016 Apr 12.

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): October 1, 2011
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: October 26, 2010
• First Submitted That Met QC Criteria: November 8, 2010
• First Posted (Estimate): November 9, 2010

Study Record Updates

• Last Update Posted (Estimate): November 27, 2012
• Last Update Submitted That Met QC Criteria: November 26, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: osteoarthritis; nuclear medicine; macrophages
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: Pro00018123; Protocol H7L-MC-MDAB(b) (Other Grant/Funding Number: Eli Lilly and Company)