An Eight Week, Double-Blind Efficacy Study of Armodafinil Augmentation to Alleviate Fibromyalgia Fatigue

Condition(s) targeted: Fibromyalgia, Primary

Intervention: armodafinil (Drug); placebo (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: State University of New York - Upstate Medical University

Overall contact:
Thomas l schwartz, MD, Phone: 315-464-3166, Email: schwartt@upstate.edu

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: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Brief Fatigue Inventory

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

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

Thomas l schwartz, MD, Phone: 315-464-3166, Email: schwartt@upstate.edu

SUNY Upstate Medical University, Syracuse, New York 13210, United States; Recruiting
Thomas L Schwartz, MD, Phone: 315-464-3166, Email: schwartt@upstate.edu
Thomas L Schwartz, MD, Principal Investigator

Starting date: August 2007
Ending date: December 2009
Last updated: June 29, 2009