Short summary

A parallel, randomized, double-blinded, placebo controlled clinical trial investigating if low dose naltrexone (LDN) is superior to placebo in reducing pain and improving pain sensitivity in patients with fibromyalgia. As secondary outcomes a possible effect on other fibromyalgia symptoms will be explored. As explorative outcomes changes in muscular exhaustion and physical fitness will be investigated. Blood will be collected for a biobank with the purpose of measuring possible changes in inflammatory cytochines during the treatment. 

Rationale

The use of Low Dose Naltrexone (LDN) as off-label treatment of pain is increasing in Denmark despite very sparse evidense. Regarding the effect of LDN on pain only 2 small clinical trials have been published. In both studies the effect of 4.5 mg LDN was tested against placebo. The first study was a single blinded pilot study including 10 women with fibromyalgia. The second study was a double-blinded randomized trial with a cross-over design including 31 women with fibromyalgia. Both studies showed LDN to be superior to placebo in reducing pain. A small clinical trial including 12 women with fibromyalgia has shown a significant reduction in inflammatory cytochines after 12 weeks of treatment med LDN. 

Our study group has carried out a dose-respons study (publication under review) including 25 women with fibromyalgia. We estimated the effective dose in 95 % (ED95) to be 5,4 mg LDN. We found that doses up to 6 mg was well tolerated. 

This study is the first larger parallel randomized, double-blinded, placebo controlled study to investigate if LDN is superior til placebo in reducing pain in patients with fibromyalgia. Patients will be titrated up to 6 mg, but if there is problems with tolerability they can be maintained at a lower dose. The treatment period is 12 weeks, including a 4 week titration phase. 

Description of the cohort

Women aged 18-64 years with a diagnosis of fibromyalgia.

Data and biological material

Questionnaire data.

Muscle exhaustion test - physical fitness tests. 

Pain sensitivity tests. 

Blood tests. 

Collaborating researchers and departments

Department of Anesthesiology and Intensive Care, Odense University Hospital

• Consultant, Karin Bruun Plesner
• Professor Palle Toft, PhD, Dr. Med.
• Consultant Karin Bruun Plesner, PhD student
• M.Sc. Henrik Bjarke Vaegter, PhD, Post. doc. 
• Consultant Morten-Rune Blichfeldt-Eckhardt, PhD, Post. doc. 

Department of Rheumatology, Frederiksberg Hospital

• Consultant Kirstine Amris, Dr. Med

Department of Orthopedics and Traumatology, Odense University Hospital

• M.Sc. Anders Holsgaard Larsen, PhD, Associate Professor

Publications associated with the project

Information about the trial is published at ClinicalTrials.gov and EUDRACT. 

The protocol will be published in an international peer-reviewed journal.

Results from the study is planned to be published in international peer-reviewed journals. Both positive, negative and inconclusive results will be published.