A Longitudinal Study of Osteoarthritis (OA) Disease Progression Measured by MRI, dGEMRIC, and Radiography

Sponsor

University of California, San Francisco (Other)

Overall Status

Completed

CT.gov ID

NCT00505297

Collaborator

Pfizer (Industry)

Enrollment

Location

Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

In order to design future disease modifying osteoarthritis drug (DMOAD) proof of concept studies, this study is being conducted to assess magnetic resonance imaging (MRI) measurements of cartilage morphology and glycosaminoglycan (GAG) content as it relates to the progression of disease in subjects with potentially rapidly progressing OA. The subject population is selected to have higher likelihood of having rapidly progressing OA (i.e., a more rapid joint space narrowing (JSN) compared to general knee OA population and thus, may be more likely to have changes in GAG content and/or cartilage volume. The results of this study may provide a reasonable means to assess DMOAD activity of drugs in development. The non-OA controls are included to determine the rate of change for subjects of similar age. Ideally, results of this study will identify reliable methods for delayed Gadolinium Enhanced MRI of cartilage (dGEMRIC) and MRI cartilage assessment that correlate with OA disease progression as compared to x-ray changes.

Condition or Disease	Intervention/Treatment	Phase
Osteoarthritis

Detailed Description

The objective of the study are:

Evaluate OA progression by evaluating cartilage morphology, cartilage glycosaminoglycan (GAG) content, and joint space changes measured by MRI (3.0T), dGEMRIC index, and radiography, respectively using age-matched control subjects to identify disease related changes.
Identify subject characteristics associated with more rapidly progressing OA.
Identify most sensitive efficacy endpoints for future DMOAD proof of concept (POC) studies.
Establish time interval for future studies based on MRI endpoints.
Evaluate the effect of contrast agent on MRI cartilage morphology and T2 measurements
Define criteria for classifying cartilage legions/deficits using dGEMRIC and T2 measurements.
Collect biofluid samples for future validation of disease specific biomarkers.

Study Design

Study Type:

Observational

Actual Enrollment :

18 participants

Observational Model:

Case-Control

Time Perspective:

Other

Official Title:

A Longitudinal Study of Osteoarthritis (OA) Disease Progression Measured by MRI, dGEMRIC, and Radiography

Study Start Date :

Aug 1, 2004

Actual Study Completion Date :

Jul 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
A Subjects with potentiall rapidl progressing OA
B Age-matched healthy subjects with no knee pain

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Female patients evaluated to be relatively in good health
40 years old and above
Negative pregnancy test

Additional inclusion criteria for OA patients:

Frequent knee symptoms in the past year, defined as:
pain, aching, or stiffness on most days of a month during the past year
use od medication (all types) for treatment of knee pain on most days of a month during the past year
Kellgren & Lawrence Grades 2 or 3 of the study knee (with either the same or less severe OA , or no OA in the contralateral knee)
Body mass index (BMI) of 30 and above
Medial joint space width of 2 mm and above

Additional inclusion criteria for age-matched controls:

BMI of 28 and above
No evidence of knee OA in either knee (i.e., Kellgren & Lawrence Grade 0 diagnosed by x-ray on AP view; infrequent knee pain, aching, stiffness during the past year; infrequent use of medication (all types) for treatment of knee pain during the past year.

Exclusion Criteria:

Anticipated need for knee surgery in the next 2 years
OA predominantly in the lateral tibiofemoral compartment measured by PA x-ray view of the study knee
Intra-articular steroids to study joint (3 month washout), intra-articular hyaluronic acid to the study joint (3 month-washout), doxycycline (3 month washout), or arthroscopy within the last 6 months
Medial joint space width less than 2 mm measured by PA view of knee x-ray
History of joint replacement, intra-articular fracture, osteotomy, arthroplasty, or meniscectomy of the study knee
History of other diseases that may involve the study joint including inflammatory joint diseases, crystalline disease, endocrinopathies, metabolic, diseases, knee infection of the study knee, neuropathic disorders, avascular necrosis, Paget's disease, or tumors (chondrocalcinosis is acceptable; treated thyroid disease is acceptable)
Systemic inflammatory diseases (e.g., Rheumatoid arthritis)
Other pain that the principal investigator feels can not be distinguished from knee pain (e.g., lumbar pain, hip pain, trochanteric bursitis)
Musculoskeletal pain that may preclude the subject from remaining motionless for the MRI acquisitions
Unable to undergo an MRI exam of the knee because of contraindications
Unable to receive gadopentate contrast agent injection because of contraindications. A study subject who displays any sign of an allergic reaction to the contrast agent will be withdrawn from the dGEMRIC part of the protocol and will not receive any subsequent contrast agent injection. The subject may continue to complete the remainder fo the study, which includes MR morphometry scan, collection of blood and urine sample for biomarker assays, and completion of study questionnaires.
Clinical chemistry laboratory values more than 2 times the upper limit of normal
Participation in clinical trial with a study during in the past 14 days
Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with trial participation or may interfere with the interpretation of trial results and, in the judgment of the investigator, would make the subject inappropriate for entry in the this trial

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California - San Frnacisco	San Francisco	California	United States	94107

Sponsors and Collaborators

University of California, San Francisco
Pfizer

Investigators

Principal Investigator: Sharmila Majumdar, PhD, University of California, San Francisco
Principal Investigator: Thomas M. Link, M.D., University of California, San Francisco