Placebo In Chronic Back Pain - Double-Blind Randomized Control Trial

Below is a detailed description of what the study would entail (in other words, what would
be expected during each visit for the duration of the study).

- Visit 1 (week -2): Pre-treatment screening (180 min). Participants will complete the
informed consent process and are evaluated for inclusion/exclusion criteria. A
medical/pain history and physical examination will be completed and participants will
be asked to assess current back pain intensity on a VAS scale (0-100mm, no pain to
worst possible pain). Participants complete questionnaires and return within 2 weeks
for baseline MR imaging scans. Blood will be drawn for a baseline screen to obtain a
complete blood count, chemistry panel, and liver function tests. Participants will be
asked to discontinue their current pain medications 14 days (2 weeks) prior to their
baseline visit and take only acetaminophen rescue medication during this time.

- Visit 2 (week 0): Baseline visit (60-90 min). Participants complete the VAS pain scale,
and if their pain is above a designated level and no changes in clinical status are
reported, they complete a battery of questionnaires and undergo fMRI procedures
(anatomical and functional scans). Participants will then be randomized to one of three
groups: active treatment, or placebo, or no-treatment groups; this is done in a
partially blind fashion (explained below), with medication dispensed in sufficient
quantities until the next visit. The placebo group will receive two placebo capsule
bid, and the standard of care group will receive one naproxen capsule (500mg) and one
esomeprazole capsule (20 mg) bid for the treatment period. The active and placebo
treatment groups are double-blinded, meaning that neither the participant nor the
researchers will know which treatment participants are receiving (in part through the
use of identical re-encapsulation of study agents). The no-treatment group allocation
is not blind, as both participants and study staff will be aware that these
participants are not receiving study agent. The no treatment group and all participants
assigned to a treatment group will continue to receive rescue medication (n=20).

- Visit 3 (week 2): End of Treatment Period 1/Washout (60-90 min). All procedures will be
performed as described for Visit 2. A set of questionnaires will be administered.
Adherence will be assessed by pill counts, use of rescue medication documented, and
participants will be queried about any side effects experienced. Only rescue medication
will be dispensed, to all participants, as they will begin a one week washout of
treatment.

- Visit 4 (week 3): End of Washout/Beginning Treatment Period 2 (60-90 min). All
procedures will be performed as described for Visit 3, plus the addition of brain
scans. Adherence will be assessed by use of rescue medication documented, and
participants will be queried about any side effects experienced. Study medication will
be dispensed in sufficient quantities until the next visit. All participants remain
with the same treatment assignment as in Period 1.

- Visit 5 (week 5): End of Treatment Period 2/Washout 2 (60-90 min). All procedures will
be performed as described for Visit 3, with the addition of post-treatment imaging
scans. Adherence will be assessed by pill counts, use of rescue medication documented,
and participants will be queried about any side effects experienced. Only rescue
medication will be dispensed.

- Visit 6 (week 6): End of Washout 2 (90 min). Participants will return to complete
questionnaires but no imaging studies will be conducted. Use of rescue medication and
side effects will be documented. Exit interviews will be conducted at this time.

- Interim periods: During weeks in between visits, participant data will be tracked with
the assistance of a smart phone/computer application designed for the study. Depending
upon preference, the research staff will download an app onto participants' phones or
give them a link to use on their computers; in the case that a participant does not
have a smart phone or easy access to a computer/internet, the study will provide
him/her with a smart phone that has the app already installed. Participants will be
given a login and will be asked to use this application twice a day right after they
take their medication. The app asks participants to rate the severity of their pain and
their mood on a Likert scale, and probes them as to whether or not they took their
medication.

Inclusion Criteria:

- History of low back pain for a minimum of 6 months with signs and symptoms of
radiculopathy: positive straight leg raising test with dermatomal radiation and/or
myotomal weakness and/or reflex asymmetry; pain must radiate into buttock or below.

- Male or female, age greater than18 years, with no racial/ethnic restrictions.

- Must have a Visual Analog Scale (VAS) pain score >50 mm (of 100 mm maximum) at the
baseline visit (for which 0mm = no pain, and 100 mm = worst pain imaginable).

- Must be able to read and speak English and be willing to read and understand
instructions as well as questionnaires.

- Must be in generally stable health.

- Must sign an informed consent document after a complete explanation of the study
documenting that they understand the purpose of the study, procedures to be
undertaken, possible benefits, potential risks, and are willing to participate.

Exclusion Criteria:

- Low back pain associated with any systemic signs or symptoms, e.g., fever, chills.

- Evidence of rheumatoid arthritis, ankylosing spondylitis, acute vertebral fractures,
fibromyalgia, history of tumor in the back.

- Other comorbid chronic pain or neurological conditions.

- Involvement in litigation regarding their back pain or having a disability claim or
receiving workman's compensation or seeking either as a result of their low back
pain.

- Diagnosis of current depression or psychiatric disorder requiring treatment, or such
a diagnosis in the previous 6 months.

- Beck Depression Inventory II score of >28.

- Use of therapeutic doses of antidepressant medications (i.e., tricyclic depressants,
SSRIs, SNRIs; low doses used for sleep may be allowed).

- Significant other medical disease such as unstable diabetes mellitus, congestive
heart failure, coronary or peripheral vascular disease, chronic obstructive lung
disease, or malignancy.

- History of gastrointestinal ulcer during the past year.

- History of myocardial infarction in the past year.

- Uncontrolled hypertension.

- Renal insufficiency.

- Allergic to, or non-tolerant of, NSAIDs.

- History of aspirin-sensitive asthma.

- Regular use of low dose aspirin.

- Current use of recreational drugs or history of alcohol or drug abuse.

- Any change in medication for back pain in the last 30 days.

- High dose opioid prophylaxis, as defined as > 50mg morphine equivalent/day.

- Any medical condition that in the investigator's judgment may prevent the individual
from completing the study or put the individual at undue risk.

- In the judgment of the investigator, unable or unwilling to follow protocol and
instructions.

- Evidence of poor treatment compliance, in the judgment of the investigator.

- Intra-axial implants (e.g. spinal cord stimulators or pumps).

- All exclusion criteria for MR safety: any metallic implants, brain or skull
abnormalities, tattoos on large body parts, and claustrophobia.

- Pregnancy, or inability to use an effective form of contraception in women of
child-bearing age.

- Diabetes (Type I or Type II).

Prohibited Medications:

- Therapeutic doses of antidepressant medications (i.e., tricyclic depressants, SSRIs,
SNRIs; low doses used for sleep may be allowed).

- Oral iron supplementation unless approved by the investigator.