An Eight Week, Double-Blind Efficacy Study of Armodafinil Augmentation to Alleviate Fibromyalgia Fatigue
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
- Brief Fatigue Inventory [ Time Frame: 8wk ] [ Designated as safety issue: No ]
|Study Start Date:||August 2007|
|Study Completion Date:||December 2009|
|Primary Completion Date:||June 2009 (Final data collection date for primary outcome measure)|
Placebo Comparator: A,2