Milnacipran for Chronic Pain in Knee Osteoarthritis

If you are in this study, you will be placed in one of two study groups: one group will
receive the study drug and one will receive a placebo. You will be assigned a study group by
chance using a process similar to the flip of a coin.

At the first visit (week one) we will review and sign the informed consent, obtain your
medical health history, and conduct a brief physical exam. You will also complete several
questionnaires about your pain. You will be assessed for your eligibility to participate in
this study. If you are eligible, we will conduct some physical and sensory tests and
collect a blood sample. The physical tests include a stair climb, 6-minute treadmill test
and a 1-minute sit to stand test. The sensory tests allow us to understand your perception
of various stimuli such as vibration, light touch, pinprick, heat, cold, hot pain, and cold
pain. At the end of the first visit you will be given an electronic diary to record your
pain throughout the study. We will also ask you to wear a device in a T-shirt, similar to
an accelerometer, that will be used to record your sleep quality and physical activity for 2
days.

At the second (week two) and third visits (week nine) you will be asked to complete the same
questionnaires, physical and sensory tests as during the first visit. You will also have to
wear the t-shirt with the device for 2 days after each visit.

Inclusion Criteria:

- Knee pain and osteophytes on radiographs OR

- Knee pain plus patient age of 40 years or older, morning stiffness lasting 30
minutes or less, and crepitus (cracking sound) during motion

- Experiences chronic pain for 6 months or longer

- Average pain rating of worse knee is equal to 4 or greater on a 0-10 scale

- If female, is not pregnant or breast feeding, and not currently attempting to
conceive; if of childbearing potential, use of a highly effective method of birth
control (as determined by Pl)

- Able to walk at least ½ a city block a day, and agrees to try and slowly increase
that over the course of study

- Able to read and speak English and provide informed consent

- Able to understand and comply with all data collection methodology including
electronic diary

- Subject agrees to 1) continue their stable drug regimen with no changes during the
course of study, 2) only use Tylenol 325 mg of tablets (a maximum of 8 tablets a day)
for breakthrough pain, and 3) not use Tylenol or any other pain medicines 12 hours
before testing.

Exclusion Criteria:

- Subject takes SNRIs (Savella, Cymbalta, Venlafaxine) or other neuroamine re-uptake
blockers for mood disorders

- Subject is allergic to SSRIs, SNRIs, or milnacipran

- Subject has severe or untreated psychiatric disturbance (e.g. mania, depression,
anxiety, substance dependence)

- Subject is medicated with 'triptans, MAOIs, SSRIs, other SNRIs, tricyclic or
heterocyclic antidepressants, lithium, epinephrine, norepinephrine, clonidine or
digoxin during the trial

- Subject has a clinical diagnosis of fibromyalgia

- Subject has severe ongoing or unaddressed medical conditions (e.g. Renal or
Hepatic disease [creatinine>1.5 ml/dl; AST or ALT> 3x normal limit], uncontrolled
hypertension, severe cardiac rate or rhythm disorders, rheumatologic disease (e.g.
polymyalgia rheumatica), narrow angle glaucoma, hyponatremia, clotting disorders,
uncontrolled seizure disorder or urinary retention)

- Subject has cardiac implants

- Subject has a knee replacement

- Subject plans to start new pain treatments or therapies during the study (e.g. new
pain medication, injections, PT, surgery)