Clinical trial: fMRI Evaluation of Pain Central Sensitization Phenomena in Subjects With Knee Osteoarthritis (NCT01700634)

Eligibility criteria:
Inclusion Criteria:

          -  Patients:

               1. A diagnosis of knee OA and suitable for the study as determined by a responsible
                  physician, based on a medical evaluation including medical history, physical
                  examination, laboratory tests and cardiac monitoring.

               2. Have a radiological and clinical diagnosis of knee OA based upon American College
                  of Rheumatology (ACR) criteria (1986) affecting at least one knee of a minimum of
                  3 months in symptom duration prior to screening.

               3. Subject is either male or female and at least 45 years of age.

               4. A minimum of 4 out of 10 on the numerical rating scale (Brief Pain Inventory- BPI
                  item 5) at screening and/ or a requirement for the use of an analgesic for the
                  pain in the OA knee. In addition, baseline pain must be stable for at least 72
                  hours prior to fMRI assessment or fMRI assessment may be delayed.

               5. A maximum of 8 out of 10 on the NRS at screening. Enrolment may be delayed if, in
                  the opinion of the investigator, the severity of pain represents an isolated
                  incident.

               6. A female subject is eligible to participate if she is of non-childbearing
                  potential.

               7. Body weight <120kg.

               8. Capable of giving written informed consent, which includes compliance with the
                  requirements and restrictions listed in the consent form.

               9. Subject demonstrates an understanding of the study and a willingness to
                  participate as evidenced by voluntary written informed consent.

          -  Controls:

               1. Subject is either male or female and at least 45 years of age.

               2. Absence of clinically relevant neurologic and psychiatric disease and history of
                  head trauma with loss of consciousness.

               3. Absence of non-compensated medical diseases and pain disorders that may
                  relevantly affect brain function and pain perception.

               4. No clinical evidence of knee OA.

               5. A female subject is eligible to participate if she is of non-childbearing
                  potential.

               6. Body weight <120kg.

               7. Capable of giving written informed consent, which includes compliance with the
                  requirements and restrictions listed in the consent form.

               8. Subject demonstrates an understanding of the study and a willingness to
                  participate as evidenced by voluntary written informed consent.

        Exclusion Criteria:

          1. - Subjects will not be permitted to heavily exercise for 12 hours prior to fMRI
             assessment

          2. - Subjects will be required to refrain from the following treatments: I.- Analgesic
             and anti-inflammatory drugs for 3 days prior to fMRI assessment except for rescue
             medication. Rescue medication will be based on paracetamol (dosed 1g/8h), which in any
             case must be withdrawn for a minimum of 24 h prior to fMRI assessment or the fMRI
             assessment may be delayed.

        II.- Steroid injections into the joint or muscle for three months prior to fMRI assessment
        III.- Hyaluronan injections into index knee within the previous 6 months prior fMRI
        assessment IV.- Non-pharmacological treatments, such as heat wraps or massage for 24 hours
        prior to fMRI assessment.

        V.- Antidepressants not allowed: MAOIs, Tricyclic antidepressants, mixed 5HT & NE reuptake
        inhibitors (eg. Duloxetine). SISR are not allowed as a recent prescription, moreover they
        are allowed in case of chronic use (more than 6 weeks). If those drugs are used for less
        than 6 weeks, patients could participate in the study after a washout period.

        VI.- Anticonvulsant indicated as a pain killer are not allowed, but patients could
        participate in the study after a washout period.

        VII.- Patients can take low doses of hypnotic drugs (eg. Lorazepam 1mg/OD or Diazepam
        5mg/OD) if they are used as a chronic prescription (more than 6 weeks). If they are used
        for less than 6 weeks, patients could participate in the study after a washout period.

        Subjects will be allowed to take their chronic (non-analgesic and non-anti-inflammatory)
        medications if the treatments have been used continuously for at least six weeks prior to
        assessment.
No condition on gender to be admitted to the trial.
Accepts Healthy Volunteers
Subject must be at least 45 Years old.


Patient description (medical language): A 47-year-old woman comes to the office complaining of pain in the calf and knee when she bends down. The pain limits her activity. Her medical history is significant for osteoarthritis, for which she uses nonsteroidal anti-inflammatory drugs (NSAIDs) for the past two years. She is living with her husband and has 3 children. She doesn't smoke but drinks alcohol occasionally. Her vital signs are normal. On physical examination, there is a small effusion in the right knee. The effusion grew a little larger and she developed a tender swelling in the popliteal fossa and calf. Both the pain and swelling worsened as she bent and straightened her knee.

Patient description (patient's own words): I'm a 47-year-old woman, married with 3 kids. I don't smoke and I drink occasionally. I went to the doctor because of pain in my calf and knee when I was bending down. This has been limiting my daily activities. I have been diagnosed with osteoarthritis for which I have taken anti-inflammatory drugs for the past 2 years. The doctor saw a small fluid buildup in my right knee. This buildup became a bit bigger and I have a swollen calf. The pain is worse when I bend and straighten my knee.

Does the patient match the trial criteria? Entailment