Clinical trial NCT00087555: Trial Comparing the Effects of Xyrem (Sodium Oxybate) With Placebo for the Treatment of Fibromyalgia
Official title: Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multi-Center Trial Comparing the Effects of Orally Administered Xyrem(R) (Sodium Oxybate) With Placebo for the Treatment of Fibromyalgia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Fibromyalgia
Keywords: Fibromyalgia
Pain
Lead sponsor: Jazz Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2004-07-14
Enrollment: 195
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether Xyrem (sodium oxybate) is effective when used alone to treat the pain and sleep disturbances of fibromyalgia.

Detailed description: Fibromyalgia affects millions of Americans, yet there are no FDA approved drugs to treat this debilitating condition. Besides causing pain, it also disrupts normal sleep patterns in many of its victims. Pain and lack of sleep reinforce each other, making patients progressively more miserable. Xyrem is a potent hypnotic that induces and consolidates sleep. In a few small studies Xyrem has been reported to offer relief to some fibromyalgia patients. This trial is designed to test this hypothesis. Patients who enroll in this study will stop taking any prescription medications for fibromyalgia (over-the-counter pain relievers will be permitted). They will then take either Xyrem alone or placebo alone. Patients will be followed for eight weeks to evaluate any relief of the pain or functional impairment of fibromyalgia from their study treatment. Sleep characteristics will also be assessed subjectively and by polysomnographic recordings at baseline and twice during the treatment phase.

Eligibility criteria: Inclusion Criteria

* Sign \& date informed consent
* Willing \& able to complete trial as described in protocol
* \> 18 years of age
* Meet American College of Rheumatology criteria for Fibromyalgia \[Widespread pain for at least 3 months, including all of the following: (1) Pain on right \& left sides of body; (2) Pain above \& below waist; (3) Pain in axial skeleton; 4) Pain on digital palpation with approximately 4kg force in at least 11 of 18 tender point sites\]
* (Study continuation) Have an average VAS pain score \> 4 on a scale of 0 to 10 as recorded in patient diary the last week before Visit 4.
* Discontinue all prescription medication taken for fibromyalgia, including opiates, benzodiazepines, anticonvulsants taken for pain, antidepressants, cyclobenzaprine (Flexeril), and/or tramadol (Ultram) until study completion
* Continue all pre-existing nutritional and/or exercise regimens and/or behavioral, massage, acupuncture, physical or cognitive therapies on an unchanged, consistent \& regular schedule throughout study
* Use only acetaminophen or over-the-counter non-steroidal anti-inflammatory drugs as rescue pain medications \& to limit dose to the labeled over-the-counter maximum. Aspirin may only be used as a cardiac protectant; formulations with caffeine are excluded.
* Forego ingestion of alcohol for duration of study.
* Fertile females must use a medically accepted method of birth control (e.g., barrier method with spermicide, oral contraceptive, or abstinence) for duration of trial.

Exclusion Criteria

1. Have any of the following medical conditions:

   * Other rheumatic disease, such as rheumatoid arthritis, osteoarthritis, or systemic lupus erythematosis
   * Uncontrolled hypo- or hyper-thyroidism of any type
   * Unstable cardiovascular, endocrine, neoplastic (excluding localized basal cell carcinoma), gastrointestinal, hematologic, hepatic, immunologic, metabolic, neurological, pulmonary, and/or renal disease which would place patient at risk during trial or compromise objectives outlined in protocol
   * Myocardial infarction within last six months
   * On their screening PSG (polysomnogram) have an Apnea Index greater than 10 per hour or an Apnea Hypopnea Index greater than 15 per hour. Note: patients with sleep apnea are not excluded if their indices are below these thresholds while sleeping with CPAP (Continuous Positive Airway Pressure) and they are compliant with CPAP therapy.
   * Problems that, in the investigator's opinion, would preclude the patient's participation and completion of this trial or compromise reliable representation of subjective symptoms.
   * If a patient will have to discontinue antidepressant medication taken for depression, the investigator must make an evaluation as to any risks from cessation of anti-depressant therapy. If, in the opinion of the investigator, a reasonable risk of resultant patient harm exists, patient is excluded from study participation
   * Current or recent history of substance abuse including alcohol abuse
   * History of seizure disorder, history of head trauma, migraine headaches or intracranial surgery, \& are taking anticonvulsants
   * Succinic semialdehyde dehydrogenase deficiency
2. Have taken any of these therapies:

   * gamma-hydroxybutyrate (sodium oxybate) in 30 days prior to signing informed consent
   * any investigational therapy in 30 days prior to signing informed consent
   * ever taken anticonvulsants to treat epilepsy or any other convulsions
3. Unwilling to stop these therapies during course of trial:

   * anticonvulsants prescribed solely for pain
   * all antidepressants
   * medication for sleep
4. Have any of the following clinical laboratory results:

   * Serum creatinine \> 2.0 mg/dL
   * TSH (Thyroid Stimulating Hormone) \< 0.3 μU/mL OR TSH \> 6 μU/mL
   * abnormal liver function tests (SGOT \[AST\] or SGPT \[ALT\] more than twice the upper limit of normal)
   * elevated serum bilirubin (more than 1.5 times the upper limit of normal)
   * pre-trial ECG with arrhythmia, greater than a first degree AV block
   * positive pregnancy test at any time during trial
5. Have any of the following socio-economic factors:

   * Pending worker's compensation litigation or related other monetary settlements
   * Have an occupation that requires variable shift work or routine night shifts

Primary outcomes:
measure: The Primary Outcome Measure Was a Composite of Changes From Baseline in Three Co-primary Self Report Measures: Pain Visual Analog Scale (PVAS, Electronic Diaries), Fibromyalgia Impact Questionnaire (FIQ), and Patient Global Impression of Change (PGI-C).
timeFrame: Baseline to week 8
Secondary outcomes:
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Radiant Research
state: Arizona
city: Beverly Hills
country: United States
facility: Osteoporosis Medical Center
state: California
city: Los Angeles
country: United States
facility: Wallace Rheumatic Study Center
state: California
city: Miami
country: United States
facility: Miami Research Associates
state: Florida
city: West Palm Beach
country: United States
facility: Radiant Research, Inc.
state: Florida
city: Lexington
country: United States
facility: Central Kentucky Research Associates, Inc.
state: Kentucky
city: Shreveport
country: United States
facility: LSU Health Sciences Center
state: Louisiana
city: Springfield
country: United States
facility: Richard N. Podell, MD
state: New Jersey
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Lenoir
country: United States
facility: Alvin Daughtridge Arthritis Center
state: North Carolina
city: Raleigh
country: United States
facility: C.A.R.E. Center
state: North Carolina
city: Middlebrook Heights
country: United States
facility: Cleveland Sleep Center
state: Ohio
city: Oklahoma City
country: United States
facility: Lynn Health Science Institute
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Duncansville
country: United States
facility: Altoona Center for Clinical Research
state: Pennsylvania
city: Katy
country: United States
facility: Abigail Rebecca Neiman, MD
state: Texas
city: San Antonio
country: United States
facility: The University of Texas Health Science Center
state: Texas
city: Sandy
country: United States
facility: Stress Medicine Clinic -- HealthSouth Rehabilitation Hospital
state: Utah
city: Renton
country: United States
facility: Pacific Rheumatology Research, Inc.
state: Washington
city: Seattle
country: United States
facility: Seattle Rheumatology Associates
state: Washington
Study officials:
affiliation: Jazz Pharmaceuticals, Inc
name: Yanping Zheng, MD
role: STUDY_DIRECTOR
References:
citation: A randomized, double blind, placebo-controlled multicenter trial comparing the effects of three doses of orally administered sodium oxybate with placebo for the treatment of narcolepsy. Sleep. 2002 Feb 1;25(1):42-9.
citation: A 12-month, open-label, multicenter extension trial of orally administered sodium oxybate for the treatment of narcolepsy. Sleep. 2003 Feb 1;26(1):31-5.
citation: U.S. Xyrem Multicenter Study Group. Sodium oxybate demonstrates long-term efficacy for the treatment of cataplexy in patients with narcolepsy. Sleep Med. 2004 Mar;5(2):119-23. doi: 10.1016/j.sleep.2003.11.002.
citation: The abrupt cessation of therapeutically administered sodium oxybate (GHB) does not cause withdrawal symptoms. J Toxicol Clin Toxicol. 2003;41(2):131-5. doi: 10.1081/clt-120019128.
citation: Scharf MB, Baumann M, Berkowitz DV. The effects of sodium oxybate on clinical symptoms and sleep patterns in patients with fibromyalgia. J Rheumatol. 2003 May;30(5):1070-4.
citation: Russell IJ, Perkins AT, Michalek JE; Oxybate SXB-26 Fibromyalgia Syndrome Study Group. Sodium oxybate relieves pain and improves function in fibromyalgia syndrome: a randomized, double-blind, placebo-controlled, multicenter clinical trial. Arthritis Rheum. 2009 Jan;60(1):299-309. doi: 10.1002/art.24142.