Plain English Summary
Background and study aims
Fibromyalgia is a long-term condition that causes pain all over the body. Chronic (long-term) pain, including fibromyalgia, affects 1 in 3 Canadians and costs around $650 billion/year in North America. Current therapies are not always effective and have a lot of side-effects at high doses. Rational combination therapy (treatment with several drugs) with different drugs to treat fibromyalgia has shown potential for measurable improvements in pain relief, quality of life and healthcare usage. Today, more than 50% of fibromyalgia patients are taking two or more pain-relieving medications at once but combination use is based on little evidence. Research is urgently needed to identify safer, more effective, combinations. The aim of this study is to test a promising combination of pregabalin, a sedating drug that is used to treat epilepsy and fibromyalgia pain, and alpha-lipoic acid, a non-sedating antioxidant that is effective for neuropathic (nerve) pain and currently being studied for efficacy in fibromyalgia.
Who can participate?
Patients aged 18 and older with fibromyalgia
What does the study involve?
Participants are allocated to be treated with pregabalin, alpha-lipoic acid, and a combination of both drugs over three treatment periods in a random order. All drugs are taken by mouth daily with an increasing dose over a 45-day period, followed by 11 days at a decreasing dose. After the three treatment periods there are two final telephone follow-ups 2 weeks and 3 months later.
What are the possible benefits and risks of participating?
The results of this study will help to improve the treatment of fibromyalgia, particularly if the combination of drugs is found to work better than either drug alone. The risks and benefits of this study are the same as the risks and benefits of each of the drugs, pregabalin and lipoic acid. The benefits of pregabalin are pain relief, improved sleep and reduced anxiety. The benefits of lipoic acid are pain relief. The most common risks of pregabalin are dizziness, drowsiness and slowed mental function. The risks of lipoic acid are nausea and vomiting (only at doses greater than 1200mg/day).
Where is the study run from?
Queen's University (Canada)
When is the study starting and how long is it expected to run for?
May 2017 to November 2020
Who is funding the study?
1. Canadian Institutes of Health Research (Canada)
2. Strategy for Patient-Oriented Research (Canada)
3. Chronic Pain Network (Canada)
Who is the main contact?
Dr Ian Gilron
Randomized controlled trial of a pregabalin-lipoic acid combination for the treatment of fibromyalgia
The combination of pregabalin and alpha-lipoic acid has superior analgesic efficacy versus either single agent for fibromyalgia.
Queen’s University Health Sciences and Affiliated Teaching Hospitals Research Ethics Board, 03/03/2017, ref: ANAE-313-17
Double-blind randomised three-period crossover trial
Primary study design
Secondary study design
Randomised cross over trial
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
There are three treatment arms that cross over as per a balanced Latin square design.
Group 1: Participants receive oral pregabalin, administered twice daily, starting at a dose of 75 mg once daily and titrated to individual maximally tolerated dose over 45 days and followed by an 11-day dose taper and washout period
Group 2: Participants receive oral alpha-lipoic acid, administered twice daily, starting at a dose of 300 mg once daily and titrated to individual maximally tolerated dose over 45 days and followed by an 11-day dose taper and washout period
Group 3: Participants receive oral pregabalin and alpha-lipoic acid administered at the above doses, titrated to individual maximally tolerated dose over 45 days and followed by an 11-day dose taper and washout period
Upon completion of the trial after the three treatment periods, there will be two final telephone follow-ups at 2 weeks and 3 months after trial completion.
Pregabalin, alpha-lipoic acid
Primary outcome measures
Mean daily pain, measured using a 0-10 numerical rating scale with 0 = no pain, 10 = worst pain imaginable, averaged over the maximally tolerated dose fixed dose week (days 39-45) of each treatment period
Secondary outcome measures
1. Pain, measured by 0-10 numerical rating scale at baseline and daily throughout entire trial
2. Pain, measured by short-form McGill Pain Questionnaire at baseline and during maximal tolerated dose of each of the three treatment periods
3. Drug doses, measured in milligrams over the 7-day maximal tolerated dose phases of each of the three treatment periods
4. Adverse events, measured in % frequency over the titration phases, maximal tolerated dose phases and dose taper/washout phases of each of the three treatment periods
5. Global relief, measured with the global relief category scale during the maximal tolerated dose phases of each of the three treatment periods
6. Pain interference, measured with the Brief Pain Inventory and the Fibromyalgia Impact Questionnaire at baseline and during the maximal tolerated dose phases of each of the three treatment periods
7. Mood, measured with the Beck Depression Inventory-2 at baseline and during the maximal tolerated dose phases of each of the three treatment periods
8. Anxiety, measured with the Beck Anxiety Inventory at baseline and during the maximal tolerated dose phases of each of the three treatment periods
9. Quality of life, measured with the SF-36 survey at baseline and during the maximal tolerated dose phases of each of the three treatment periods
10. Blinding, measured with a blinding questionnaire during the maximal tolerated dose phases of each of the three treatment periods
11. Acetaminophen consumption, measured in milligrams during the dose taper/washout phases of each of the three treatment periods
Overall trial start date
Overall trial end date
Participant inclusion criteria
2. Daily pain (≥3/10) for at least 3 months
3. AST/ALT ≤120% upper limit of normal
4. Creatinine clearance ≥60 ml/min
5. Necessary abilities, visual acuity, and language skills for questionnaire completion and phone communication with research personnel
6. Adults over the age of 18
Target number of participants
Participant exclusion criteria
1. Patients with major organ system disease, moderate to severe sedation or ataxia due to other required drugs, hypersensitivity to study medications, seizure disorder, or other painful condition >50% as severe as their fibromyalgia pain
2. Patients with a major, poorly controlled, psychiatric disorder, severe depression or suicidal ideation, or active substance abuse disorder
3. Patients who live alone and cannot assure daily contact with a friend, family member, or caregiver
4. Women of childbearing potential will be required to receive a highly effective form of contraception and a negative pregnancy test at baseline
5. Allergy or hypersensitivity to any of the study medications
6. Seizure disorder
Recruitment start date
Recruitment end date
Countries of recruitment
Central African Republic
Trial participating centre
Providence Care K7L2V7 99 University Ave
Canadian Institutes of Health Research
Instituts de Recherche en Santé du Canada, CIHR
Funding Body Type
Funding Body Subtype
Strategy for Patient-Oriented Research
Funding Body Type
Funding Body Subtype
Chronic Pain Network
Funding Body Type
Funding Body Subtype
Results and Publications
Publication and dissemination plan
Planned publication in a peer-reviewed journal.
IPD sharing plan:
The datasets generated during and/or analysed during the current study will be available upon request from Dr Ian Gilron.
Intention to publish date
Participant level data
Available on request
Results - basic reporting
2017 protocol in: https://www.ncbi.nlm.nih.gov/pubmed/28778847