Low Dose Naltrexone for Treatment of Pain in Patients With Fibromyalgia - Effect Via a Central Mechanism? (LDN-in-FM)
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|ClinicalTrials.gov Identifier: NCT02806440|
Recruitment Status : Recruiting
First Posted : June 20, 2016
Last Update Posted : August 23, 2016
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.
It is a 2-center study that takes place at The Multidisciplinary Pain Center in Copenhagen and at The Multidisciplinary Pain Center in Give.
|Condition or disease||Intervention/treatment||Phase|
|Fibromyalgia||Drug: Low dose naltrexone Drug: Placebo||Phase 4|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||140 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|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 Start Date :||June 2016|
|Estimated Primary Completion Date :||August 2017|
|Estimated Study Completion Date :||December 2017|
Active Comparator: Low dose naltrexone
Low dose naltrexone 4.5 mg/tablet, 1 tablet a day for 21 days
Drug: Low dose naltrexone
Other Name: Naltrexone
Placebo Comparator: Placebo
1 tablet a day for 21 days
Other Name: Inert substance
- Change in pain scores (during rest, during household activity, during personal daily hygienic procedures) [ Time Frame: 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 ]The patient indicates using a questionnaire-based numerical rating scale (0 = no pain; 100 = worst imaginable pain) mean values of pain at rest, pain during household activity and pain during personal hygienic procedures in the preceding 24 hrs. The cumulated pain scores are used in the statistical analyses.
- Fibromyalgia Impact Questionnaire Revised (FIQR) [ Time Frame: 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 ]
The FIQR is a fibromyalgia-specific questionnaire containing three domains: function domain, impact domain and symptom domain. The total score of FIQR is calculated by:
- the function domain sum is divided by 3 (upper limit 30)
- the impact domain sum is unchanged (upper limit 20)
- the symptom domain sum is divided by 2 (upper limit 50) The three resulting processed domain scores are summed to obtain the total score of the FIQR (range 0-100)
- Daily Sleep Interference Scale (DSIS) [ Time Frame: Diary (Treatment 1: baseline (Day 1) to Day 21; Treatment 2: baseline (Day 35) to Day 56) ]Pain-related sleep interference is evaluated with the DSIS (0 =pain does not interfere with sleep, 10 = pain completely interferes with sleep]).
- Pressure algometry (1 sq.cm probe) [ Time Frame: Treatment 1: Baseline (Day 1) + Day 14 + Day 21; Treatment 2: Baseline (Day 35) + Day 49 + Day 56 ]
Pressure algometry in pre-specified points:
- right occipital region at insertion of m. subocipitalis
- right m. trapezius at the midpoint of the upper border
- right paraspinal region, 3 cm lateral of the midline at level of mid-scapula
- right second costochondral junction
- right lateral epicondyle
- right knee region, at the medial "fat pad" proximal of the meniscus margin
In addition at following control sites:
- right lower arm, at the dorsal lower third
- right fingernail of first digit
- right third metatarsal bone at midpoint Cut-off point is 400 kPa, rate 10-30 kPa/s
- Hospital Anxiety and Depression Scale (HADS) [ Time Frame: Treatment 1: Baseline (Day 1) + Day 14 + Day 21; Treatment 2: Baseline (Day 35) + Day 49 + Day 56 ]HADS is a 14-item questionnaire used to evaluate the subject's level of anxiety and depression; the subjects can rate between 0-21 with a score of eleven as the cutoff point for anxiety or depression
- Pain Catastrophizing Scale (PCS) [ Time Frame: Treatment 1: Baseline (Day 1) + Day 14 + Day 21; Treatment 2: Baseline (Day 35) + Day 49 + Day 56 ]The PCS is a 13-item self-report scale to measure pain catastrophizing: each item is rated on a 5-point nominal scale (0 = not at all, 4 = all the time). It is constructed with three subscales being magnification, rumination, and helplessness.
- Adverse effects [ Time Frame: Diary + Treatment 1: Baseline (day 1) + Day 14 + Day 21; Treatment 2: Baseline (Day 35) + Day 49 + Day 56 ]
Self-reported adverse effects related to the treatment:
CNS: irritability, mood changes, drowsiness, lethargy, sleep dysfunction, dizziness cardiovascular system: palpitations, orthostatic hypotension g.i.-system: dyspepsia, nausea, obstipation, diarrhoea urogenital system: urinary retention, urinary incontinence autonomic system: diaphoresis, shivering
- Quantitative Sensory Testing (QST) [ Time Frame: Treatment 1: Baseline (Day 1) + Day 14 + Day 21; Treatment 2: Baseline (Day 35) + Day 49 + Day 56 ]
Cold pressor test (1min, 10C) - Pressure tolerance threshold before and after Cold Water.
Heat/Capsaicin test - 5min, 45C heat, followed by 30min capsaicin cream 0.075%, Measurement of allodynic (brush, Somedic) and hyperalgesic (Pinprick stimulator 128nm) areas.
- Plasma concentrations of naltrexone and β-Naltrexon [ Time Frame: Treatment 1: Baseline (Day 1) + Day 14 + Day 21; Treatment 2: Baseline (Day 35) + Day 49 + Day 56 ]
- Pain DETECT [ Time Frame: Treatment 1: Baseline (Day 1) + Day 14 + Day 21; Treatment 2: Baseline (Day 35) + Day 49 + Day 56 ]Measurement of neuropathic component
- Brief Pain Inventory - Short Form (BPI-SF) questionnaire [ Time Frame: Before baseline: Day -3 to -1; Washout: Before baseline Day 32 to 34 ]
BPI-SF allows patients to rate the severity of their pain and the degree to which their pain interferes with common dimensions of feeling and function.
BPI-SF is a widely used Measurement Tool for assessing clinical pain.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02806440
|Contact: Mads U Werner, PhD, MDfirstname.lastname@example.org|
|Contact: Trine Andresen, PhDemail@example.com|
|Multidisciplinary Pain Centre||Recruiting|
|Give, Denmark, 7323|
|Contact: Trine Andresen, PhD firstname.lastname@example.org|
|Principal Investigator:||Anette Bendiksen, MD||Multidisciplinary Pain Clinic|