Trial record 51 of 134 for:    fibromyalgia | Open Studies | Interventional Studies

Low Dose Naltrexone for Treatment of Pain in Patients With Fibromyalgia - Effect Via a Central Mechanism? (LDN-in-FM)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified June 2016 by Rigshospitalet, Denmark
Sponsor:
Information provided by (Responsible Party):
Mads Werner, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier:
NCT02806440
First received: June 16, 2016
Last updated: June 22, 2016
Last verified: June 2016
  Purpose

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 Intervention Phase
Fibromyalgia
Drug: Low dose naltrexone
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by Rigshospitalet, Denmark:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

    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) ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: Yes ]
  • Pain DETECT [ Time Frame: Treatment 1: Baseline (Day 1) + Day 14 + Day 21; Treatment 2: Baseline (Day 35) + Day 49 + Day 56 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

    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.



Estimated Enrollment: 140
Study Start Date: June 2016
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Low dose naltrexone
Low dose naltrexone 4.5 mg/tablet, 1 tablet a day for 21 days
Drug: Low dose naltrexone
Active comparator
Other Name: Naltrexone
Placebo Comparator: Placebo

Placebo tablet

1 tablet a day for 21 days

Drug: Placebo
Placebo comparator
Other Name: Inert substance

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

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02806440

Contacts
Contact: Mads U Werner, PhD, MD mads.u.werner@gmail.com
Contact: Trine Andresen, PhD 004579718098 trine.andresen2@rsyd.dk

Sponsors and Collaborators
Rigshospitalet, Denmark
Investigators
Principal Investigator: Anette Bendiksen, MD Multidisciplinary Pain Clinic
  More Information

Publications:

Responsible Party: Mads Werner, MD, PhD, DMSc, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier: NCT02806440     History of Changes
Other Study ID Numbers: 2015-002972-26 
Study First Received: June 16, 2016
Last Updated: June 22, 2016
Health Authority: Denmark: Danish Health and Medicines Authority
Denmark: Ethics Committee
Denmark: Danish Dataprotection Agency
Individual Participant Data  
Plan to Share IPD: Yes
Plan Description: Anonymized IPD will be made available in a public research database as part of the final publication.

Keywords provided by Rigshospitalet, Denmark:
Low dose naltrexone
Pain

Additional relevant MeSH terms:
Fibromyalgia
Myofascial Pain Syndromes
Muscular Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Neuromuscular Diseases
Nervous System Diseases
Naltrexone
Narcotic Antagonists
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on July 28, 2016