An Eight Week, Double-Blind Efficacy Study of Armodafinil Augmentation to Alleviate Fibromyalgia Fatigue
Condition: Fibromyalgia, Primary
MeSH terms: Fibromyalgia; Myofascial Pain Syndromes
Intervention: armodafinil; placebo
Intervention description: 50-250mg/d; matching placebo
Intervention MeSH terms: Modafinil
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 55.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: fibromyalgia; fatigue

Summary:

      Armodafinil (NuvigilTM) is an isomer of a drug currently approved by the FDA for the
      treatment of fatigue secondary to narcolepsy, sleep apnea, and shift work sleep disorder
      called modafinil (ProvigilTM). There is considerable off label evidence for modafinil's
      ability to reduce fatigue related to multiple sclerosis, Parkinson's disease, cancer related
      fatigue, and depression related fatigue. There are preclinical studies showing that modafinil
      can alleviate fatigue secondary to medication side effects (diazepam, chlorpromazine). This
      multi-layered evidence base suggests that modafinil may be able to alleviate fatigue
      regardless of medical illness. Armodafinil now has four completed Phase III FDA regulatory
      studies revealing that it is well tolerated and effective for fatigue associated with
      obstructive sleep apnea (Effects of Armodafinil in the Treatment of Residual Excessive
      Sleepiness Associated with Obstructive Sleep Apnea/Hypopnea Syndrome: A 12-Week, Multicenter,
      Double-Blind, Randomized,Placebo-Controlled Study in nCPAP-Adherent Adults. Thomas Roth et
      al. Clinical Therapeutics/Volume 28, Number 5, 2006), shift work sleep disorder, and
      narcolepsy. Armodafinil is not yet FDA approved. It is felt to be a cleaner, safer, more
      potent isomer. Theoretically, fatigue is interpreted and possibly dictated centrally and
      armodafinil's proposed mechanism (similar to that of modafinil) of elevating central
      histamine activity may allow the brain to interpret a lower fatigue state, thus allowing
      patients to function better during the day with less peripheral fatigue.

      Fibromyalgia (FM) is an illness that may involve medical, rheumatological, 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 all have randomized trials and
      almost all focus on pain. There are very few studies, if any, that look at FM induced fatigue
      which certainly ads to FM patients' daily incapacity and lowered productivity/quality of
      life.

      Armodafinil is a drug with minimal adverse effects (headache, insomnia, GI distress, anxiety,
      dry mouth, dizziness and an assumed low level addiction which is comparable to modafinil)
      which is well tolerated in current regulatory studies. It may have a safer tolerability
      profile than the FM medications noted above. As modafinil is often studied and often added as
      an augmentation agent to patients' regimens who suffer from fatigue in other medical
      illnesses, the authors feel that armodafinil would also be effective in this population. The
      authors wish to conduct a study to determine if armodafinil is safe and tolerable in the
      treatment of FM induced fatigue. This initial controlled study may allow for continued
      regulatory studies with this product in FM subjects. We propose a double-blind placebo
      controlled study to determine if armodafinil is safe and effective in reversing FM induced
      fatigue.
    

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 x2 years due to medical
             condition or surgery

          -  Have been formally diagnosed by a Board Certified Rheumatologist using the ACR 1990
             research criteria for fibromylagia

          -  Report that fatigue, in addition to FM pain is a key distressing symptom of their FM

          -  Have a score of >4 on the Brief Fatigue Inventory (BFI)

          -  Women of child bearing potential must agree to use barrier contraception as
             armodafinil may decrease the effectiveness of oral contraceptives

        Exclusion Criteria:

          -  Exclusion: 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 180 days (outside
             of nicotine)

          -  Use other stimulating medication ie stimulants, caffeine products (this refers to OTC
             stimulants OR patients clinically tolerant to and withdrawing from caffeinated
             beverages, bupropion, desipramine, etc UNLESS said drug has been in steady dosing for
             >4 weeks

          -  Have a known medical condition outside of FM that causes fatigue (i.e. obstructive
             apnea, hypothyroidism, depression, etc)

          -  Have a known medical condition or other medication use that relatively contraindicates
             armodafinil use (ie substance abuse, sensitivity to armodafinil, known cardiac
             abnormalities of left ventricular hypertrophy, recent MI, mitral valve prolapse
             dependent on stimulant use, history of psychosis

          -  Has a prior history of modafinil use and failure

          -  Be receiving daytime sedating medication with clear chronological impact on fatigue
             UNLESS fatigue predates sedating medication or said medication has been steadily dosed
             > 4 weeks

          -  Medications that induce/inhibit p450 3A4 as they may alter armodafinil plasma levels,
             and vica versa