Cyclobenzaprine Extended Release (ER) for Fibromyalgia
Condition: Fibromyalgia; Pain; Sleep; Fatigue
MeSH terms: Fibromyalgia; Myofascial Pain Syndromes; Fatigue
Intervention: cyclobenzaprine ER (AMRIX); placebo
Intervention description: active drug; matching placebo for AMRIX
Intervention MeSH terms: Cyclobenzaprine
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 37.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: fibromyalgia; Pain; Sleep; Fatigue

Summary:

      Amrix (Cyclobenzaprine hydrochloride Extended release capsules) is approved by the FDA as a
      muscle relaxant, indicated for the treatment of muscle spasm associated with acute, painful
      musculoskeletal conditions. Cyclobenzaprine ER (Amrix TM) has a distinct pharmacokinetic
      profile providing early systemic exposure and consistent plasma concentration over several
      hours. Overall, a single dose of Amrix 30 mg is similar to that of cyclobenzaprine immediate
      release 10 mg three times daily. This ER formula should improve compliance, with similar
      efficacy and possibly less side effects as is often the case with slower release
      formulations.

      There are clinical studies showing that cyclobenzaprine can alleviate pain secondary to
      Fibromyalgia induced muscle tone. This multi-layered evidence base suggests that
      cyclobenzaprine may be able to alleviate pain in fibromyalgia. Theoretically in fibromyalgia,
      pain is interpreted centrally and possibly occurs due to said muscle spasm . Cyclobenzaprine
      may relieve this pain, thus allowing patients to function better during the day and sleep
      better at night. Cyclobenzaprine has tricyclic antidepressant structure which may also allow
      pain signal dampening in the spinal cord as well, similar to amitriptyline which is used
      off-label for neuropathic pain as well.

      Fibromyalgia (FM) is an illness that may involve medical, rheumatologic, autoimmune, sleep,
      endocrine and psychiatric pathology. It is a syndrome of recurrent pain at trigger points.
      Greater than 90% of these patients will report fatigue as a key symptom as well. There are
      several investigation lines into the treatment of FM induced pain. Exercise, behavioral
      therapy, amitryptiline, duloxetine, tramadol, sodium oxybate, pregabalin all have randomized
      trials and almost all focus on pain. There are very few studies evaluating cyclobenzaprine
      and none studying to Cyclobenzaprine ER formulation. None evaluate pain reduction, sleep and
      fatigue improvement.

      Cyclobenzaprine is a drug with minimal adverse effects (dry mouth, dizziness, fatigue,
      constipation, somnolence, nausea, and dyspepsia). It may have a safer tolerability profile
      than some of the FM medications noted above. As cyclobenzaprine is often studied and often
      added as an augmentation agent to patients' regimens who suffer from acute painful
      musculoskeletal conditions, the authors feel that cyclobenzaprine would also be effective in
      this population. The authors wish to conduct a study to determine if cyclobenzaprine ER is
      safe and tolerable in the treatment of FM induced pain, and secondary fatigue and insomnia.
      This initial study may allow for continued regulatory studies with this product in FM
      subjects. The authors propose a double-blind placebo controlled study to determine if
      cyclobenzaprine ER is safe and effective in reversing FM induced pain, and secondary fatigue
      and insomnia.
    

Eligibility criteria:

        Inclusion Criteria:

        If possible, 60 subjects will be included in this study.

          -  All males/females of any race are eligible if aged between 18 and 65 and

          -  Subjects must speak English and have capacity to receive and utilize informed consent

          -  Agree to use barrier method contraception or are infertile x 2 years due to medical
             condition or surgery

          -  Have been formally diagnosed by a Board Certified Rheumatologist using the ACR 1990
             research criteria for fibromyalgia

          -  Report that pain is a key distressing symptom of their FM

          -  Have a score of > 4 on the Visual Analogue Pain Scale (VAPS)

        Exclusion Criteria: Subjects cannot

          -  Be pregnant or be attempting to conceive at present (urine bHCG must be negative)

          -  Have an active substance abuse problem with last use within the past 90 days (outside
             of nicotine)

          -  Use cardiac QTc prolonging medications i.e., tricyclic antidepressants

          -  Use p4502D6 major inhibiting medications as cyclobenzaprine levels may increase

          -  Have a known medical condition outside of FM that causes pain, i.e., diabetic
             neuropathy

          -  Have a known medical condition or other medication use that relatively contraindicates
             cyclobenzaprine use (i.e., hypersensitivity concomitant use of monoamine oxidase (MAO)
             inhibitors, seizures, known cardiac abnormalities, recent MI. hepatitis, stroke, or
             psychosis

          -  Has a prior history of cyclobenzaprine use and failure (failure due to side effects
             may be allowed at P.I. discretion)

          -  Be receiving daytime/nighttime sedating medication with clear chronological impact on
             fatigue UNLESS fatigue predates sedating medication or said medication has been
             steadily dosed > 4 weeks

          -  Other medications known to alleviate pain (i.e., Gabapentin, Pregabalin,
             Amitryptiline, Duloxetine,Venlafaxine, Carbamazepine, Tramadol, etc) unless they have
             been at steady dose more than 6 weeks