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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 : Unknown
Verified August 2016 by Mads Werner, Rigshospitalet, Denmark.
Recruitment status was:  Recruiting
First Posted : June 20, 2016
Last Update Posted : August 23, 2016
Sponsor:
Information provided by (Responsible Party):
Mads Werner, Rigshospitalet, Denmark

Tracking Information
First Submitted Date  ICMJE June 16, 2016
First Posted Date  ICMJE June 20, 2016
Last Update Posted Date August 23, 2016
Study Start Date  ICMJE June 2016
Estimated Primary Completion Date August 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 17, 2016)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 17, 2016)
  • 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:
    1. right occipital region at insertion of m. subocipitalis
    2. right m. trapezius at the midpoint of the upper border
    3. right paraspinal region, 3 cm lateral of the midline at level of mid-scapula
    4. right second costochondral junction
    5. right lateral epicondyle
    6. right knee region, at the medial "fat pad" proximal of the meniscus margin
    In addition at following control sites:
    1. right lower arm, at the dorsal lower third
    2. right fingernail of first digit
    3. 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Low Dose Naltrexone for Treatment of Pain in Patients With Fibromyalgia - Effect Via a Central Mechanism?
Official Title  ICMJE Low Dose Naltrexone for Treatment of Pain in Patients With Fibromyalgia - Effect Via a Central Mechanism? A Randomized, Double-blinded, Placebo-controlled, Crossover Study.
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.

It is a 2-center study that takes place at The Multidisciplinary Pain Center in Copenhagen and at The Multidisciplinary Pain Center in Give.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Fibromyalgia
Intervention  ICMJE
  • Drug: Low dose naltrexone
    Active comparator
    Other Name: Naltrexone
  • Drug: Placebo
    Placebo comparator
    Other Name: Inert substance
Study Arms  ICMJE
  • Active Comparator: Low dose naltrexone
    Low dose naltrexone 4.5 mg/tablet, 1 tablet a day for 21 days
    Intervention: Drug: Low dose naltrexone
  • Placebo Comparator: Placebo

    Placebo tablet

    1 tablet a day for 21 days

    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: June 17, 2016)
140
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2017
Estimated Primary Completion Date August 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Denmark
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02806440
Other Study ID Numbers  ICMJE 2015-002972-26
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Anonymized IPD will be made available in a public research database as part of the final publication.
Responsible Party Mads Werner, Rigshospitalet, Denmark
Study Sponsor  ICMJE Rigshospitalet, Denmark
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Anette Bendiksen, MD Multidisciplinary Pain Clinic
PRS Account Rigshospitalet, Denmark
Verification Date August 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP