Placebo In Chronic Back Pain (Phase 2)
Condition: Chronic Low Back Pain
MeSH terms: Back Pain; Low Back Pain
Study type: Interventional
Phase: Phase 4

Summary: 
      This study is designed to examine brain properties for placebo response in chronic back pain
      patients. The investigators have preliminary data indicating that, in blinded clinical trial
      studies with neutral instructions regarding treatment, chronic back pain (CBP) patients can
      be subdivided into placebo responders and non-responders, and these differences are
      PREDICTABLE a priori, by brain activity. The results imply that CBP placebo may have clinical
      utility and that its properties can be studied by human brain imaging techniques. In Phase I
      of the study, the investigators seek to identify brain imaging parameters that predict the
      propensity for the placebo response in an independent CBP cohort. In Phase II, the
      investigators will evaluate the interaction between placebo response and medication treatment
      in individuals stratified as placebo responders versus non-responders. This research is
      designed to critically assess the neurobiology of placebo analgesia for chronic pain in a
      partially-blind clinical trial.
    

Detailed description: 
      Visit 1 (week -3): Screening visit (90 min):

      Participants will be evaluated with inclusion/exclusion criteria and complete the informed
      consent documents. A medical/pain history will be taken and physical exam will be completed
      by a physician and participants will be asked to rate their current back pain intensity.
      Participants will complete a set of 10 questionnaires that will ask about health and medical
      history, past and current pain levels, personality, and emotions. Participants will be
      allowed to take breaks and walk around during this time so that participants don't get tired
      while filling out questionnaires. Finally, participants will have blood drawn for screening
      purposes including to see if kidneys and liver are functioning as they should (the
      investigators will take 40 mL or about 8 teaspoons). Participants will be asked to return in
      2 weeks for baseline magnetic resonance imaging (MRI) scans. Participants will be asked to
      discontinue current pain medications 14 days prior to Visit 2 and take only the rescue
      medication ("rescue" medication that is also known as acetaminophen/Tylenol ®), given for
      pain during this time (see below) - this is so that the investigators can assess baseline
      amount of pain. Participants will be informed that they may be randomized in the placebo
      group and/or the no-treatment group (Visit 3) once one qualifies to continue in the study.
      Participants must, therefore,a be willing and able to stop taking the medication for pain for
      up to a maximum of 12 weeks during this study. Participants will be given acetaminophen (500
      mg, up to 4 times per day) to take for pain relief (as rescue medication), a dose that can be
      continued throughout the study. Participants are free to stop participation at any point in
      the study. Participants randomized into the treatment arm may receive the anti-inflammatory
      drug naproxen, since it is known to increase the risk of stomach and intestinal side effects,
      a combined naproxen/esomeprazole drug regimen will be given to participants to provide some
      protection for these types of side effects.

      Visit 2 (week -1): Baseline Scan (90 min):

      Participants will rate their pain intensity, complete questionnaires, and undergo brain
      scanning (anatomical and functional scans). Participants will receive medication, which can
      be used if the pain becomes too much to handle (500 mg four times per day maximum). The
      researcher will ask participants about how often participants used the "rescue" medication
      and any changes in health they may have experienced since the last visit.

      Visit 3 (week 0): Start of Treatment Period and Randomization (30-45 min):

      Participants will rate their pain intensity and complete questionnaires. Participants will be
      randomized into either a drug (placebo or naproxen and esomeprazole) treatment group or no
      treatment group; if participants are assigned to a treatment group (active or placebo),
      neither participants nor the clinical coordinator/assistant will know which group
      participants are allocated in. Enough medication will be given to participants to last until
      the next visit. The placebo group will receive two placebo capsules twice daily and the
      active drug group will receive one naproxen capsule (500mg) and one esomeprazole capsule
      (20mg) twice daily (morning and night) for the treatment period. The medication (Naproxen or
      Placebo) needs to be taken with at least one full glass (8 oz) of water and the other
      medication (Esomeprazole or Placebo) should be taken one hour before a meal. The researcher
      will provide the study medication; if participants were randomized into the no treatment
      group, participants will only receive rescue medication. The researcher will ask participants
      about how often participants used the "rescue" medication and any side effects participants
      experienced since Visit 2 took place. Additional "rescue" medication will be given.

      Visit 4 (week 3): Continuing Assessment (30-45 min). The procedures described for Visit 3
      will be repeated during this visit. The researcher will ask participants about how often they
      used the "rescue" medication and any side effects experienced since Visit 3 took place. As
      well, the researcher will ask how often participants took the study medication (if in a
      treatment group) and document the total pills ingested.

      Visit 5 (week 6): End of Treatment/Start of Washout and Final Scan (60-90 min):

      The procedures described for Visit 2 will be repeated during this visit. The researcher will
      ask participants about how often and reliably participants took the medication (if in a
      treatment group), as well as how often they used the "rescue" medication and any side effects
      experienced since Visit 4 took place. Participants will only receive the "rescue" medication
      for the upcoming 3 weeks.

      Visit 6 (week 9): Final Visit/End of Washout (30-45 min):

      Participants will return to complete questionnaires, but no brain scans will be done. The
      researcher will ask participants about how often they used the "rescue" medication and any
      side effects experienced since Visit 5 took place. If participants are in one of the
      treatment groups, participants will be asked to return all of the study medication and rescue
      medication at this time, and all treatment will be stopped at this visit.
    

Intervention name(s): Naproxen; Omeprazole; Placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Subjects enrolled in the active treatment arm will receive 500mg of Naproxen prescribed twice daily, once in the morning and evening.; Subjects enrolled in the active treatment arm will receive 20mg of Omeprazole prescribed twice daily, once in the morning and evening. Furthermore, subjects should take this one hour before a meal.; Subjects enrolled in the inactive treatment arm will receive two prescriptions, however, there are no active ingredients and are intended to look identical to the active treatment. Therefore, subjects will be instructed exactly the same way as if they were ingesting the active treatment.
Other intervention name(s): Aleve; Anaprox; Antalgin; Feminax Ultra; Flanax; Inza; Midol Extended Relief; Nalgesin; Naposin; Naprelan; Naprogesic; Naprosyn; Narocin; Proxen; Soproxen; Synflex; Xenobid; Prilosec; Iosepine; Sugar Pill
Intervention MeSH terms: Naproxen; Omeprazole
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: chronic; low back; back; pain; brain; MRI