Patient case (clinical description): A 66-year-old woman comes to the office due to joint pain in the hands and periodic morning stiffness that lasts less than 15 minutes.  The pain is moderately severe and worsens with daily activity. The patient used Tylenol with minimal relief.  Past medical history is notable for hypertension and hypercholesteremia.  Physical examination shows firm nodules over the distal interphalangeal joints, bilaterally. The patient has pain in her knees as well. The knees are stiff in the morning for less than 30 minutes and become worse with climbing stairs. She has some sensation of bone friction during activity. X-ray shows narrowing of the joint space, subchondral bone sclerosis and osteophyte formation along the joints.

Patient's own account: I'm a 66-year-old woman and I went to my doctor's office because of a bloody joint pain in my hands that has been lasting for a while. The pain comes and go in the morning usually. I feel like a stiffness that last less than 15 minutes. The pain is moderately severe but it gets worse when I'm using my hands. I used Tylenol which helped a little. Apart from that, I suffer from hypertension and high cholesterol. The doctor made me notice that I have bumps around both of my hand joints. I also suffer from my knees and they are also stiff in the morning for around 30 min. It's even worse when I climb up the stairs! I also feel like my bones are rubbing against each other when I'm moving. The X-ray showed that I have narrow joint space, I have sclerosis, and abnormal growths of bone along my joints.

Clinical trial: Safety, Tolerability, and Efficacy of IA Verapamil in the Treatment of Joint Pain in Subjects With Osteoarthritis of the Knee

Eligibility criteria:
Inclusion Criteria:

        Subjects must meet all of the following inclusion criteria to participate in the study:

          1. Be 35-75 years of age and in good general medical and psychological health.

          2. Be able to speak, read, write, and understand English, understand the consent form,
             complete study-related procedures, and communicate with the study staff.

          3. Have OA of at least 1 knee (target knee) for at least 6 months and meet all the
             following criteria:

               -  OA documented by standing X-rays anterior-posterior patella-femoral view taken
                  within 1 month of screening visit indicating Kellgren-Lawrence Grade 2 to
                  early-stage Grade 4 radiographic stage of the knee;

               -  Have pain associated with OA of the target knee for at least 25 of the last 30
                  days; c. Meet the American College of Rheumatology clinical classification
                  criteria, defined as having pain in the target knee and at least 3 of the
                  following 6 items:

                    -  Age > 50;

                    -  Morning stiffness <30 minutes;

                    -  Crepitus on active motion;

                    -  Bony tenderness;

                    -  Bony enlargement;

                    -  No palpable warmth of synovium.

          4. Target knee does not have any type of orthopedic and/or prosthetic device.

          5. Based on standard physical examination of the target knee, does not have any
             neurovascular deficits, any skin abnormalities, any meniscal abnormalities, or any
             ligament instability.

          6. At treatment visit 2 prior to randomization, have a score of at least 20 on the WOMAC
             pain subscale (questions 1-5) for the target knee and an in-clinic average pain
             intensity score of at least 4/10 on the 0-10 NRS for the 24-hour recall.

          7. Be willing to maintain any present stable treatment modalities (e.g., acupuncture or
             physical therapy) and be willing to refrain from initiating any new treatment
             modalities.

          8. Be willing to stop taking nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids
             for the duration of the study.

          9. If female of child-bearing potential (ie, not medically or surgically sterilized or
             not post-menopausal more than 1 year) or fertile male with sexual partner of
             childbearing potential, be willing to use adequate and reliable contraception
             throughout the study (eg, abstinence or barrier with additional spermicidal foam or
             jelly, or the use of intrauterine device or hormonal contraception by female subjects
             and partners of male subjects).

         10. Not be enrolled in any other clinical trial and not have used any investigational drug
             within 1 month.

        Exclusion Criteria:

        Subjects who meet any of the following criteria will not be eligible to participate:

          1. Have a Kellgren-Lawrence Grade 1 radiographic stage of the knee or have
             Kellgren-Lawrence Grade 4 radiographic end stage of the knee with bone on bone, ie,
             less than 2 mm joint space.

          2. Be a candidate for knee replacement within next 6 months.

          3. Have a body mass index > 35 kg/m2.

          4. Have a Hospital Anxiety and Depression Scale score >12 on either subscale or have an
             established history of major depressive disorder not controlled with medication.

          5. Have, in the Investigator's opinion, clinically significant abnormalities in clinical
             laboratory tests (hematology, clinical labs, urinalysis).

          6. Have a positive urine drug test for illegal drug substances at screening.

          7. Have, in the Investigator's opinion, clinically significant abnormalities in
             electrocardiogram readings

          8. If a female of childbearing potential, have a positive pregnancy test at screening.

          9. Have significant pain outside the target knee, including significant hip or back pain
             (bilateral knee OA will be allowed as long as target knee pain can be distinguished
             from contralateral knee pain and contralateral knee does not require treatment).

         10. Have pain affecting the target knee that is due to any etiology other than OA.

         11. Have documented history of inflammatory arthritis, including rheumatoid arthritis.

         12. Have a meniscal tear in the target knee.

         13. Have had viscosupplementation with hyaluronic acid products within 6 months prior to
             screening.

         14. Have failed to respond to prior treatment with viscosupplementation with hyaluronic
             acid products.

         15. Have had IA corticosteroid injections within 12 weeks or intramuscular or oral
             steroids within 4 weeks prior to screening.

         16. Have had surgery of the target knee within 6 months prior to screening.

         17. Have used opioids 4 or more days per week during in the past month prior to screening.

         18. Are allergic to, or intolerant of, acetaminophen.

         19. Have used verapamil within the past 4 weeks or are allergic or intolerant to
             verapamil.
No condition on gender to be admitted to the trial.
Accepts Healthy Volunteers
Subject must be at least 35 Years old.
Subject must be at most 75 Years

Eligibility (NLI label): Entailment