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 Overview

• Status: Completed
• Conditions: Fibromyalgia, Primary
• Intervention / Treatment: Drug: placebo; Drug: armodafinil

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A,1; armodafinil	Drug: armodafinil; 50-250mg/d
Placebo Comparator: A,2; placebo	Drug: placebo; matching placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brief Fatigue Inventory	This scale measures overall fatigue due to medical illness. range is 0-80 with 80 being severe fatigue	8 weeks

Collaborators and Investigators

• Sponsor: State University of New York - Upstate Medical University

Study record dates

Study Major Dates

• Study Start: August 1, 2007
• Primary Completion (Actual): June 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: May 13, 2008
• First Submitted That Met QC Criteria: May 14, 2008
• First Posted (Estimate): May 15, 2008

Study Record Updates

• Last Update Posted (Estimate): December 18, 2014
• Last Update Submitted That Met QC Criteria: December 9, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: fatigue; fibromyalgia
• Additional Relevant MeSH Terms: Nervous System Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Muscular Diseases; Neuromuscular Diseases; Fibromyalgia; Myofascial Pain Syndromes; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Central Nervous System Stimulants; Wakefulness-Promoting Agents; Modafinil
• Other Study ID Numbers: ArmoFibro-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No