Clinical trial NCT02806440: Low Dose Naltrexone for Treatment of Pain in Patients With Fibromyalgia - Effect Via a Central Mechanism?
Official title: Low Dose Naltrexone for Treatment of Pain in Patients With Fibromyalgia - Effect Via a Central Mechanism? A Randomized, Double-blinded, Placebo-controlled, Crossover Study.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Fibromyalgia
Keywords: Low dose naltrexone
Pain
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
First posted: 2016-06-20
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This study evaluates the effect and mechanism of low dose naltrexone for treatment of pain in patients with fibromyalgia. It s a randomised, double-blinded, placebo-controlled, cross-over study.

The study takes place at The Multidisciplinary Pain Center in Grindsted.

Detailed description: Fibromyalgia syndrome is a prevalent musculoskeletal disorder characterized by pain, profound fatigue, sleep disorder, mood disturbance etc. The prevalence is estimated to be 2-8%.

Treatment of pain in patients with fibromyalgia is often based on opioids. However, opioids may lead to tolerance, addiction and hyperalgesia and alternative treatments are therefore warranted.

Low dose naltrexone (3-5mg) (LDN) has shown promising results in the treatment of pain in patients with fibromyalgia, but there is a need for further research.

At the typical dose of naltrexone, 50 mg, it is an opioid antagonist. However LDN demonstrates analgesic and anti-inflammatory effects, possibly involving an antagonism of microglia in the CNS.

The investigators hypothesize, that LDN has a better pain relieving effect than placebo in in patients with fibromyalgia (FM). The investigators also hypothesize that LDN has a better effect upon experimentally induced pain in FM-patients, compared to placebo. A tentative mechanism is a central facilitation of the endogenous pain inbitory system.

Eligibility criteria: Patients diagnosed with fibromyalgia based on the criteria of American College of Rheumatology.

Inclusion Criteria:

* Widespread pain in patients with fibromyalgia (based on the above criteria)
* Enrolled as a patient in one of the multidisciplinary pain clinics involved in the project
* Inflammatory rheumatic disease (peripheral inflammation, including arthritis), must be excluded
* Women must be treated with a contraceptive measure, if not menopausal

Exclusion Criteria:

* Cancer
* Treatment with opioids (other analgesic treatments in stabile dose 14 days prior to study start are allowed)
* Change in stabile treatment (p.n. paracetamol is allowed, but must be registered)
* Pregnant/breastfeeding
* Does not speak/understand Danish
* Allergy to the ingredient
* Severe liver impairment
* Severe kidney impairment
* Acute hepatitis

Primary outcomes:
measure: Change in pain scores (during rest, during household activity, during personal daily hygienic procedures)
timeFrame: Baseline: Day -2 to day 1 (baseline before treatment 1); Treatment 1: Day 19 to 21 ; Washout: Day 33 to 35 (baseline before treatment 2); Treatment 2: Day 54 to 56
Secondary outcomes:
measure: Fibromyalgia Impact Questionnaire Revised (FIQR)
timeFrame: Before baseline: Day -3; Treatment 1: Baseline (Day 1) + Day 14 + 21 ; Washout: Before baseline day -3; Treatment 2: Baseline (Day 35) + Day 49 + 56
measure: Daily Sleep Interference Scale (DSIS)
timeFrame: Diary (Treatment 1: baseline (Day 1) to Day 21; Treatment 2: baseline (Day 35) to Day 56)
measure: Pressure algometry (1 sq.cm probe)
timeFrame: Treatment 1: Baseline (Day 1) + Day 14 + Day 21; Treatment 2: Baseline (Day 35) + Day 49 + Day 56
measure: Hospital Anxiety and Depression Scale (HADS)
timeFrame: Treatment 1: Baseline (Day 1) + Day 14 + Day 21; Treatment 2: Baseline (Day 35) + Day 49 + Day 56
measure: Pain Catastrophizing Scale (PCS)
timeFrame: Treatment 1: Baseline (Day 1) + Day 14 + Day 21; Treatment 2: Baseline (Day 35) + Day 49 + Day 56
measure: Adverse effects
timeFrame: Diary + Treatment 1: Baseline (day 1) + Day 14 + Day 21; Treatment 2: Baseline (Day 35) + Day 49 + Day 56
measure: Quantitative Sensory Testing (QST)
timeFrame: Treatment 1: Baseline (Day 1) + Day 14 + Day 21; Treatment 2: Baseline (Day 35) + Day 49 + Day 56
measure: Plasma concentrations of naltrexone and β-Naltrexon
timeFrame: Treatment 1: Baseline (Day 1) + Day 14 + Day 21; Treatment 2: Baseline (Day 35) + Day 49 + Day 56
measure: Pain DETECT
timeFrame: Treatment 1: Baseline (Day 1) + Day 14 + Day 21; Treatment 2: Baseline (Day 35) + Day 49 + Day 56
measure: Brief Pain Inventory - Short Form (BPI-SF) questionnaire
timeFrame: Before baseline: Day -3 to -1; Washout: Before baseline Day 32 to 34
Other outcomes:
Locations:
city: Grindsted
country: Denmark
facility: Multidisciplinary Pain Centre
Study officials:
affiliation: Multidisciplinary Pain Clinic
name: Kirsten M Bested, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gaskin DJ, Richard P. The economic costs of pain in the United States. J Pain. 2012 Aug;13(8):715-24. doi: 10.1016/j.jpain.2012.03.009. Epub 2012 May 16.
citation: Clauw DJ. Fibromyalgia: a clinical review. JAMA. 2014 Apr 16;311(15):1547-55. doi: 10.1001/jama.2014.3266.
citation: Wolfe F, Clauw DJ, Fitzcharles MA, Goldenberg DL, Katz RS, Mease P, Russell AS, Russell IJ, Winfield JB, Yunus MB. The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity. Arthritis Care Res (Hoboken). 2010 May;62(5):600-10. doi: 10.1002/acr.20140.
citation: Gilron I, Jensen TS, Dickenson AH. Combination pharmacotherapy for management of chronic pain: from bench to bedside. Lancet Neurol. 2013 Nov;12(11):1084-95. doi: 10.1016/S1474-4422(13)70193-5. Epub 2013 Sep 25.
citation: Younger J, Parkitny L, McLain D. The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain. Clin Rheumatol. 2014 Apr;33(4):451-9. doi: 10.1007/s10067-014-2517-2. Epub 2014 Feb 15.
citation: Younger JW, Zautra AJ, Cummins ET. Effects of naltrexone on pain sensitivity and mood in fibromyalgia: no evidence for endogenous opioid pathophysiology. PLoS One. 2009;4(4):e5180. doi: 10.1371/journal.pone.0005180. Epub 2009 Apr 13.
citation: Younger J, Noor N, McCue R, Mackey S. Low-dose naltrexone for the treatment of fibromyalgia: findings of a small, randomized, double-blind, placebo-controlled, counterbalanced, crossover trial assessing daily pain levels. Arthritis Rheum. 2013 Feb;65(2):529-38. doi: 10.1002/art.37734.