Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
ANAE-172-01
Study information
Scientific title
Combination pharmacotherapy for the management of pain in fibromyalgia: a double-blind, randomised, placebo-controlled, four-period crossover trial
Acronym
Study hypothesis
A combination of duloxetine and pregabalin has a superior therapeutic profile than that of either drug alone for reducing fibromyalgia pain.
Ethics approval
Queen's University Research Ethics Board, 09/11/2010
Study design
Double-blind randomised placebo-controlled four-period crossover trial
Primary study design
Interventional
Secondary study design
Randomised cross over trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
Fibromyalgia
Intervention
1. Pregabalin-duloxetion combination
2. Pregabalin
3. Duloxetine
4. Inert placebo
As per a double-dummy, balanced Latin Square design, trial treatments are administered orally in four different treatment periods. In each of the four periods, doses of study medication are gradually titrated - over 24 days - towards each individual maximal tolerated dose and continued at that dose for seven days followed by an 11 day taper-washout period. Ceiling doses are 450 mg daily for pregabalin and 120 mg daily for duloxetine. Total duration of follow-up is 9 months.
Intervention type
Drug
Phase
Phase IV
Drug names
Duloxetine, pregabalin
Primary outcome measure
Daily pain intensity, recorded at study baseline and during each treatment at maximal tolerated dose (MTD)
Secondary outcome measures
Recorded at baseline and during each treatment at maximal tolerated dose (MTD):
1. Fibromyalgia Impact Questionnaire
2. Number of tender points
3. Medical Outcomes Study Sleep Scale
4. Global pain relief
5. Brief Pain Inventory
6. Beck Depression Inventory 2
7. Beck Anxiety Inventory
8. Short form McGill Pain Questionnaire
9. 36-item short form (SF-36) quality of life survey
10. Maximal tolerated doses of of duloxetine and pregabalin
11. Frequency/severity of other treatment-emergent adverse effects
12. Blinding questionnaires
13. Acetaminophen consumption
Overall trial start date
01/02/2011
Overall trial end date
30/01/2014
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Fibromyalgia according to American College of Rheumatology (ACR) criteria 1990
2. Experiencing daily moderate pain (greater than or equal to 4/10) for at least 3 months
3. Adults aged 18 to 70 years, either sex
4. Patients entering the study on duloxetine, gabapentinoids and other drugs which adversely interact with study drugs (e.g., selective serotonin receptor inhibitors [SSRIs], momanime oxidase inhibitors [MAOIs], tramadol etc.) must be weaned off. Participants taking less than 200 mg morphine equivalents/day are allowed to continue these medications at a steady dose.
5. Permitted analgesic medications are non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen (4 g/d) and aspirin (less than or equal to 325 mg/d for cardiac prophylaxis)
6. Serum laboratory results obtained at study entry:
6.1. Liver function tests: alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less than 1.2 times upper limit of normal
6.2. Creatinine clearance less than 1.5 times upper limit of normal
6.3. Negative serum betaHCG for women of childbearing potential
7. Adequate birth control for all women of child-bearing potential
8. Sufficient cognitive function and English language skills to complete questionnaires and communicate verbally with the nursing staff to permit titration of the study drugs
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
69
Participant exclusion criteria
1. Presence of a painful condition, including inflammatory rheumatic disease, as severe as (or worse than), but distinct from, their fibromyalgia
2. Pregnancy or lactation
3. Women of child-bearing potential not using adequate contraceptives
4. End-stage kidney or liver disease
5. Unstable cardiovascular disease (myocardial infarction [MI] within preceding year, unstable angina or congestive heart failure) or clinically relevant abnormal 12-lead electrocardiogram
6. Signs or symptoms of any central neurologic disorder (including seizures)
7. Untreated endocrine disorder
8. A severe mood disorder as diagnosed by a psychiatrist and/or active suicidal ideation
9. Hypersensitivity to any of the study medications
10. History of significant abuse of illicit drugs, prescription drugs or alcohol as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV R)
11. Patients requiring continued treatment with drugs which adversely interact with study medication (e.g. quinolone antibiotics, warfarin, SSRIs etc.)
12. Patients taking more than 200 mg morphine equivalents/day
13. Uncontrolled diabetes mellitus
14. Uncontrolled hypertension
15. Documented human immunodeficiency virus (HIV), hepatitis and other clinically relevant liver dysfunction
16. Malignant diseases (including brain tumours)
17. Subjects under other investigational studies
18. Hereditary problems of fructose intolerance, glucose galactose malabsorption or sucrose isomaltase insufficiency
19. Uncontrolled narrow-angle glaucoma
20. Continued use of MAOIs, fluvoxamine, selective serotonin reuptake inhibitors (SSRIs) and anticoagulants
Recruitment start date
01/02/2011
Recruitment end date
30/01/2014
Locations
Countries of recruitment
Canada
Trial participating centre
Kingston General Hospital
Kingston
K7L2V7
Canada
Sponsor information
Organisation
Queen's University (Canada)
Sponsor details
Department of Anesthesiology
99 University Avenue
Kingston
K7L 3N6
Canada
Sponsor type
University/education
Website
Funders
Funder type
Government
Funder name
Canadian Institutes of Health Research
Alternative name(s)
Instituts de Recherche en Santé du Canada, CIHR, IRSC
Funding Body Type
government organisation
Funding Body Subtype
National government
Location
Canada
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2016 results in: https://www.ncbi.nlm.nih.gov/pubmed/26982602