Condition category
Musculoskeletal Diseases
Date applied
12/01/2011
Date assigned
28/02/2011
Last edited
28/02/2011
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Ian Gilron

ORCID ID

Contact details

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

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 approved on the 9th November 2010

Study design

Double-blind randomised placebo-controlled four-period crossover trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below 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 measures

Daily pain intensity, recorded at study baseline and during each treatment at maximal tolerated dose (MTD)

Secondary outcome measures

Recorded at study 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

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

Department of Anesthesiology
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

http://www.queensu.ca/

Funders

Funder type

Research organisation

Funder name

Canadian Institutes of Health Research (CIHR) (Canada) - http://www.cihr-irsc.gc.ca

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

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

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes