ISRCTN ISRCTN20173707
DOI https://doi.org/10.1186/ISRCTN20173707
Secondary identifying numbers ANAE-172-01
Submission date
12/01/2011
Registration date
28/02/2011
Last edited
14/03/2017
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Musculoskeletal Diseases
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Ian Gilron
Scientific

Department of Anesthesiology
Victory 2 Pavillion
Kingston General Hospital
76 Stuart Street
Kingston
K7L2V7
Canada

Study information

Study designDouble-blind randomised placebo-controlled four-period crossover trial
Primary study designInterventional
Secondary study designRandomised cross over trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details to request a patient information sheet
Scientific titleCombination pharmacotherapy for the management of pain in fibromyalgia: a double-blind, randomised, placebo-controlled, four-period crossover trial
Study objectivesA combination of duloxetine and pregabalin has a superior therapeutic profile than that of either drug alone for reducing fibromyalgia pain.
Ethics approval(s)Queen's University Research Ethics Board, 09/11/2010
Health condition(s) or problem(s) studiedFibromyalgia
Intervention1. 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 typeDrug
Pharmaceutical study type(s)
PhasePhase IV
Drug / device / biological / vaccine name(s)Duloxetine, pregabalin
Primary outcome measureDaily pain intensity, recorded at study baseline and during each treatment at maximal tolerated dose (MTD)
Secondary outcome measuresRecorded 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 study start date01/02/2011
Completion date30/01/2014

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participants69
Key inclusion criteria1. 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
Key exclusion criteria1. 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
Date of first enrolment01/02/2011
Date of final enrolment30/01/2014

Locations

Countries of recruitment

  • Canada

Study participating centre

Kingston General Hospital
Kingston
K7L2V7
Canada

Sponsor information

Queen's University (Canada)
University/education

Department of Anesthesiology
99 University Avenue
Kingston
K7L 3N6
Canada

Website http://www.queensu.ca/
ROR logo "ROR" https://ror.org/02y72wh86

Funders

Funder type

Government

Canadian Institutes of Health Research
Government organisation / National government
Alternative name(s)
Instituts de Recherche en Santé du Canada, Canadian Institutes of Health Research (CIHR), CIHR_IRSC, Canadian Institutes of Health Research | Ottawa ON, CIHR, IRSC
Location
Canada

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 01/07/2016 Yes No

Editorial Notes

14/03/2017: Publication reference added.