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Fibromyalgia and Naltrexone: The FINAL Study (FINAL)

Primary Purpose

Fibromyalgia

Status
Completed
Phase
Phase 2
Locations
Denmark
Study Type
Interventional
Intervention
Naltrexone Pill
Placebo oral tablet
Sponsored by
Odense University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Fibromyalgia

Eligibility Criteria

18 Years - 64 Years (Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Women aged 18-64 years
  • Understands and writes Danish
  • Fulfills the American College of Rheumatology 1990 criteria for fibromyalgia
  • A minimum score of 4 in self-reported average pain during the last 7 days on a 0-10 numeric rating scale at baseline
  • All fertile women have to use safe anti conception (Spiral, birth control pills, contraceptive patch, contraceptive vaginal ring or gestagen injections) for 3 weeks before and 1 week after the trial. If the patients' normal lifestyle includes sexual abstinence, they do not have to use anti conception. Instead they can give an oral informed consent, that they will be sexually abstinent during the trial. A woman is considered non-fertile if she is sterilized, hysterectomized, bilateral oophorectomized or is postmenopausal. A woman is considered postmenopausal when vaginal bleeding has been absent for 1 year and is confirmed by measurement of follicle-stimulating hormone.

Exclusion Criteria:

  • Known allergy against naltrexonehydroclorid
  • Pregnancy or breastfeeding. A negative pregnancy test has to be available for all fertile subjects at baseline
  • Use of opioids or NSAIDs during the 4 weeks before inclusion in the trial
  • Abuse of alcohol or other substances
  • Inflammatory rheumatic diseases
  • Demyelinating diseases
  • Active cancer
  • Liver dysfunction
  • Kidney dysfunction
  • Psychotic diseases
  • History of suicide attempts
  • Suicide ideation - evaluated using Patient Health Questionnaire-9 (Item 9 has to be answered "never")

Sites / Locations

  • Pain centre, Odense University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Naltrexone

Placebo

Arm Description

Low Dose Naltrexone (LDN) is administered for 12 weeks, including a titration phase of 4 weeks. Participants will be titrated up to 6 mg following a dose escalation scheme: Initial dosage of 1.5 mg daily, escalated every seventh day by 1.5 mg up to 6 mg at week 4. Dose escalation will be based on safety and tolerability, and if dose escalation is not feasible, delayed increments are allowed. After end of titration (week 4) the subjects will be maintained at the highest tolerated dose level for the last 8 weeks of the treatment period. Subjects are not allowed to change dose during the last 8 weeks of the treatment period. The medicine is taken orally as tablets once daily in the evening.

LDN-placebo is administered for 12 weeks, including a titration phase of 4 weeks. Participants will be titrated up to 6 mg following a dose escalation scheme: Initial dosage of 1.5 mg daily, escalated every seventh day by 1.5 mg up to 6 mg at week 4. Dose escalation will be based on safety and tolerability, and if dose escalation is not feasible, delayed increments are allowed. After end of titration (week 4) the subjects will be maintained at the highest tolerated dose level for the last 8 weeks of the treatment period. Subjects are not allowed to change dose during the last 8 weeks of the treatment period. The medicine is taken orally as tablets (similar in size, shape and taste to the active medication), once daily in the evening.

Outcomes

Primary Outcome Measures

Average pain during the last 7 days
Assessed by asking the participants about the level of average pain during the last 7 days on a 11 point rating scale, ranging from 0-10 (0 = "no pain" and 10 = "unbearable pain") using the first item from the symptom part of the Fibromyalgia Impact Questionnaire Revised. A lower score indicates lower severity.

Secondary Outcome Measures

Global assessment
Measured by Patient Global Impression of Change on a 1-7 Verbal Rating Scale. The participants are asked how they rate their overall fibromyalgia symptoms after 4, 8 and 12 weeks of treatment compared with before treatment. A score of 4 indicates "no change", a score of 1 is characterized by "a lot worse" and a score of 7 is characterized by "a lot better." A higher score indicates higher degree of improvement.
Impact of fibromyalgia
Measured by the Fibromyalgia Impact Questionnaire Revised (FIQR) total score. The FIQR asks patients to rate how difficult it is to perform a list of 9 common activities over the previous 7 days on an 11 point scale, ranging from 0-10 (0 = "no difficulty" and 10 = "very difficult"). The FIQR then asks patients to indicate how often their fibromyalgia impacts their quality of life over the last 7 days on an 11 point scale, ranging from 1-10 (0 = "never" and 10 = "always"). Finally, the FIQR asks patients to assess the severity of 10 different symptoms on an 11 point scale, ranging from 0-10 (0 = "no symptoms" and 10 = "extreme symptoms"). These three sub-scales are summed to represent an overall FIQR score. A lower score indicates lower severity.
Pain distribution
Assessed by the Widespread Pain Index (WPI) from The American College of Rheumatology 2016 revised criteria for fibromyalgia (ACR-2016). The body is divided into 19 body parts and number of pain full body parts during the last 7 days is counted, giving rise to the WPI. A lower score indicates lower spreading of pain.
Level of pain
Assessed by the Fibromyalgia Impact Questionnaire Revised "level of pain" question, asking the participants to rate the average level of pain during the last 7 days on a 11 point rating scale, ranging from 0-10 (0 = "no pain" and 10 = "unbearable pain"). A lower score indicates lower severity.
Level of tenderness
Assessed by the Fibromyalgia Impact Questionnaire Revised "level of tenderness to touch" question, asking the participants to rate the average level of tenderness to touch during the last 7 days on an 11 point rating scale, ranging from 0-10 (0 = "no tenderness" and 10 = "very tender"). A lower score indicates a lower severity. AND Assessed by measurement of pressure pain threshold, using a handheld algometer. Points measured: Right Quadriceps 15 cm proximal of apex patella and left Trapezius 10 cm from acromion. Each point is measured 3 times. Pressure pain threshold is measured in kilopascal (kPa). A higher value indicates a lower severity.
Level of fatigue
Assessed by the Fibromyalgia Impact Questionnaire Revised "level of energy" question, asking the participants to rate the average level of energy during the last 7 days on an 11 point rating scale, ranging from 0-10 (0 = "lots of energy" and 10 = "no energy"). A lower score indicates a lower severity.
Level of sleep disturbance
Assessed by the Fibromyalgia Impact Questionnaire Revised "quality of sleep" question asking the participants to rate the average quality of sleep during the last 7 days on an 11 point rating scale, ranging from 0-10 (0 = "awoke well rested" and 10 = "awoke very tired"). A lower score indicates a lower severity.
Level of depression
Assessed by the Fibromyalgia Impact Questionnaire Revised "level of depression" question, asking the participants to rate the average level of depression during the last 7 days on an 11 point rating scale, ranging from 0-10 (0 = "no depression" and 10 = "very depressed"). A lower score indicates a lower severity.
Level of anxiety
Assessed by the Fibromyalgia Impact Questionnaire Revised "level of anxiety" question, asking the participants to rate the average level of anxiety during the last 7 days on an 11 point rating scale, ranging from 0-10 (0 = "not anxious" and 10 = "very anxious"). A lower score indicates a lower severity.
Level of cognition
Assessed by the Fibromyalgia Impact Questionnaire Revised "level of memory problems" question, asking the participants to rate the average level of memory problems during the last 7 days on an 11 point rating scale, ranging from 0-10 (0 = "good memory" and 10 = "very poor memory"). A lower score indicates a lower severity.
Level of stiffness
Assessed by the Fibromyalgia Impact Questionnaire Revised "level of stiffness" question, asking the participants to rate the average level of stiffness during the last 7 days on an 11 point rating scale, ranging from 0-10 (0 = "no stiffness" and 10 = "severe stiffness"). A lower score indicates a lower severity.
Level of physical function
Assessed by the physical function domain of Fibromyalgia Impact Questionnaire Revised; asking participants to rate how difficult it is to perform a list of 9 common activities over the previous 7 days on an 11 point scale, ranging from 0-10 (0 = "no difficulty" and 10 = "very difficult"). The score is characterized by the sum of the 9 scores (0-90). A lower score indicates better function.
Health-related quality of life - mobility
Measured by the European Quality of Life 5 Dimensions (EQ-5D) mobility domain; asking the participants to rate their mobility on a 1-5 Verbal Rating Scale, a score of 1 indicating no problems, and a score of 5 indicating extreme problems. A lower score indicates a lower severity.
Health-related quality of life - self care
Measured by the European Quality of Life 5 Dimensions (EQ-5D) self care domain; asking the participants to rate their ability for self care on a 1-5 Verbal Rating Scale, a score of 1 indicating no problems, and a score of 5 indicating extreme problems. A lower score indicates a lower severity.
Health-related quality of life - usual activities
Measured by the European Quality of Life 5 Dimensions (EQ-5D) usual activities domain; asking the participants to rate their ability to perform usual activities on a 1-5 Verbal Rating Scale, a score of 1 indicating no problems, and a score of 5 indicating extreme problems. A lower score indicates a lower severity.
Health-related quality of life - pain/discomfort
Measured by the European Quality of Life 5 Dimensions (EQ-5D) pain/discomfort domain; asking the participants to rate their level of pain or discomfort on a 1-5 Verbal Rating Scale, a score of 1 indicating no problems, and a score of 5 indicating extreme problems. A lower score indicates a lower severity.
Health-related quality of life - anxiety/depression
Measured by the European Quality of Life 5 Dimensions (EQ-5D) anxiety/depression domain; asking the participants to rate their level of anxiety or depression on a 1-5 Verbal Rating Scale, a score of 1 indicating no problems, and a score of 5 indicating extreme problems. A lower score indicates a lower severity.
Health-related quality of life - global
Measured by European Quality of Life Visual Analogue Scale (EQ-VAS), which asks the participant to rate their overall health 'today' on a 0-100 VAS. A higher score indicates a better quality of life.
Number of responders with a more than 15% improvement of pain
A responder is defined as a subject who reports a more than 15% improvement of the primary outcome (average pain during the last 7 days) after 12 weeks of treatment with LDN or LDN-placebo. Number of responders are calculated for both the LDN group and the LDN-placebo group.
Number of responders with a more than 30% improvement of pain
A responder is defined as a subject who reports a more than 30% improvement of the primary outcome (average pain during the last 7 days) after 12 weeks of treatment with LDN or LDN-placebo. Number of responders are calculated for both the LDN group and the LDN-placebo group.
Number of responders with a more than 50% improvement of pain
A responder is defined as a subject who reports a more than 50% improvement of the primary outcome (average pain during the last 7 days) after 12 weeks of treatment with LDN or LDN-placebo. Number of responders are calculated for both the LDN group and the LDN-placebo group.

Full Information

First Posted
January 30, 2020
Last Updated
December 28, 2022
Sponsor
Odense University Hospital
Collaborators
University of Southern Denmark, University Hospital Bispebjerg and Frederiksberg
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1. Study Identification

Unique Protocol Identification Number
NCT04270877
Brief Title
Fibromyalgia and Naltrexone: The FINAL Study
Acronym
FINAL
Official Title
Fibromyalgia and Naltrexone: The FINAL Study
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Completed
Study Start Date
January 6, 2021 (Actual)
Primary Completion Date
December 27, 2022 (Actual)
Study Completion Date
December 27, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Odense University Hospital
Collaborators
University of Southern Denmark, University Hospital Bispebjerg and Frederiksberg

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study evaluates the effect of low dose naltrexone (LDN) on pain in women with fibromyalgia (FM). The study is designed as a parallel randomized (1:1) double blind, placebo-controlled superiority trial. Half of the participants will receive treatment with LDN while the other half will receive treatment with placebo.
Detailed Description
Low dose naltrexone (LDN) is used widely as off label treatment in patients with fibromyalgia, despite the lack of larger randomized controlled trials (RCT) supporting an effect. LDN has antagonistic effect on both opioid receptors and on toll-like receptors in glia cells. Mediated via those receptors, LDN can potentially reduce neuroinflammation and induce homeostasis in the endorphin system in patients with fibromyalgia. The aim of the trial is to investigate whether treatment with LDN has a superior effect compared to placebo on pain among female patients with fibromyalgia, evaluated after 12 weeks of treatment. The study is also exploring secondary aims regarding a possible improvement of other fibromyalgia core symptoms and a possible improvement of global assessment, daily functioning and health-related quality of life. Among the exploratory secondary objectives are changes in muscle exhaustion, physical fitness, pain sensitivity, inhibition of pain, augmentation of pain, and pro-inflammatory cytokines.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fibromyalgia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
A parallel randomized (1:1) double blind, placebo-controlled superior trial
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
99 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Naltrexone
Arm Type
Experimental
Arm Description
Low Dose Naltrexone (LDN) is administered for 12 weeks, including a titration phase of 4 weeks. Participants will be titrated up to 6 mg following a dose escalation scheme: Initial dosage of 1.5 mg daily, escalated every seventh day by 1.5 mg up to 6 mg at week 4. Dose escalation will be based on safety and tolerability, and if dose escalation is not feasible, delayed increments are allowed. After end of titration (week 4) the subjects will be maintained at the highest tolerated dose level for the last 8 weeks of the treatment period. Subjects are not allowed to change dose during the last 8 weeks of the treatment period. The medicine is taken orally as tablets once daily in the evening.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
LDN-placebo is administered for 12 weeks, including a titration phase of 4 weeks. Participants will be titrated up to 6 mg following a dose escalation scheme: Initial dosage of 1.5 mg daily, escalated every seventh day by 1.5 mg up to 6 mg at week 4. Dose escalation will be based on safety and tolerability, and if dose escalation is not feasible, delayed increments are allowed. After end of titration (week 4) the subjects will be maintained at the highest tolerated dose level for the last 8 weeks of the treatment period. Subjects are not allowed to change dose during the last 8 weeks of the treatment period. The medicine is taken orally as tablets (similar in size, shape and taste to the active medication), once daily in the evening.
Intervention Type
Drug
Intervention Name(s)
Naltrexone Pill
Other Intervention Name(s)
LDN
Intervention Description
Treatment with LDN for 12 weeks, including af titration phase of 4 weeks. Initial dosage of 1.5 mg, dose is increased by 1.5 mg every 7th day to 6 mg at week 4. Dosing is increased based on safety and tolerability and delayed increments are allowed. The participants are maintained on the highest tolerable dose for the last 8 weeks of the treatment period.
Intervention Type
Drug
Intervention Name(s)
Placebo oral tablet
Other Intervention Name(s)
LDN-placebo
Intervention Description
Treatment with LDN-placebo for 12 weeks, including af titration phase of 4 weeks. Initial dosage of 1.5 mg, dose is increased by 1.5 mg every 7th day to 6 mg at week 4. Dosing is increased based on safety and tolerability and delayed increments are allowed. The participants are maintained on the highest tolerable dose for the last 8 weeks of the treatment period.
Primary Outcome Measure Information:
Title
Average pain during the last 7 days
Description
Assessed by asking the participants about the level of average pain during the last 7 days on a 11 point rating scale, ranging from 0-10 (0 = "no pain" and 10 = "unbearable pain") using the first item from the symptom part of the Fibromyalgia Impact Questionnaire Revised. A lower score indicates lower severity.
Time Frame
Change from baseline when assessed after 12 weeks of treatment with LDN or LDN-placebo
Secondary Outcome Measure Information:
Title
Global assessment
Description
Measured by Patient Global Impression of Change on a 1-7 Verbal Rating Scale. The participants are asked how they rate their overall fibromyalgia symptoms after 4, 8 and 12 weeks of treatment compared with before treatment. A score of 4 indicates "no change", a score of 1 is characterized by "a lot worse" and a score of 7 is characterized by "a lot better." A higher score indicates higher degree of improvement.
Time Frame
Change in overall fibromyalgia symptoms from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo
Title
Impact of fibromyalgia
Description
Measured by the Fibromyalgia Impact Questionnaire Revised (FIQR) total score. The FIQR asks patients to rate how difficult it is to perform a list of 9 common activities over the previous 7 days on an 11 point scale, ranging from 0-10 (0 = "no difficulty" and 10 = "very difficult"). The FIQR then asks patients to indicate how often their fibromyalgia impacts their quality of life over the last 7 days on an 11 point scale, ranging from 1-10 (0 = "never" and 10 = "always"). Finally, the FIQR asks patients to assess the severity of 10 different symptoms on an 11 point scale, ranging from 0-10 (0 = "no symptoms" and 10 = "extreme symptoms"). These three sub-scales are summed to represent an overall FIQR score. A lower score indicates lower severity.
Time Frame
Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo
Title
Pain distribution
Description
Assessed by the Widespread Pain Index (WPI) from The American College of Rheumatology 2016 revised criteria for fibromyalgia (ACR-2016). The body is divided into 19 body parts and number of pain full body parts during the last 7 days is counted, giving rise to the WPI. A lower score indicates lower spreading of pain.
Time Frame
Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo
Title
Level of pain
Description
Assessed by the Fibromyalgia Impact Questionnaire Revised "level of pain" question, asking the participants to rate the average level of pain during the last 7 days on a 11 point rating scale, ranging from 0-10 (0 = "no pain" and 10 = "unbearable pain"). A lower score indicates lower severity.
Time Frame
Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo
Title
Level of tenderness
Description
Assessed by the Fibromyalgia Impact Questionnaire Revised "level of tenderness to touch" question, asking the participants to rate the average level of tenderness to touch during the last 7 days on an 11 point rating scale, ranging from 0-10 (0 = "no tenderness" and 10 = "very tender"). A lower score indicates a lower severity. AND Assessed by measurement of pressure pain threshold, using a handheld algometer. Points measured: Right Quadriceps 15 cm proximal of apex patella and left Trapezius 10 cm from acromion. Each point is measured 3 times. Pressure pain threshold is measured in kilopascal (kPa). A higher value indicates a lower severity.
Time Frame
Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo
Title
Level of fatigue
Description
Assessed by the Fibromyalgia Impact Questionnaire Revised "level of energy" question, asking the participants to rate the average level of energy during the last 7 days on an 11 point rating scale, ranging from 0-10 (0 = "lots of energy" and 10 = "no energy"). A lower score indicates a lower severity.
Time Frame
Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo
Title
Level of sleep disturbance
Description
Assessed by the Fibromyalgia Impact Questionnaire Revised "quality of sleep" question asking the participants to rate the average quality of sleep during the last 7 days on an 11 point rating scale, ranging from 0-10 (0 = "awoke well rested" and 10 = "awoke very tired"). A lower score indicates a lower severity.
Time Frame
Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo
Title
Level of depression
Description
Assessed by the Fibromyalgia Impact Questionnaire Revised "level of depression" question, asking the participants to rate the average level of depression during the last 7 days on an 11 point rating scale, ranging from 0-10 (0 = "no depression" and 10 = "very depressed"). A lower score indicates a lower severity.
Time Frame
Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo
Title
Level of anxiety
Description
Assessed by the Fibromyalgia Impact Questionnaire Revised "level of anxiety" question, asking the participants to rate the average level of anxiety during the last 7 days on an 11 point rating scale, ranging from 0-10 (0 = "not anxious" and 10 = "very anxious"). A lower score indicates a lower severity.
Time Frame
Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo
Title
Level of cognition
Description
Assessed by the Fibromyalgia Impact Questionnaire Revised "level of memory problems" question, asking the participants to rate the average level of memory problems during the last 7 days on an 11 point rating scale, ranging from 0-10 (0 = "good memory" and 10 = "very poor memory"). A lower score indicates a lower severity.
Time Frame
Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo
Title
Level of stiffness
Description
Assessed by the Fibromyalgia Impact Questionnaire Revised "level of stiffness" question, asking the participants to rate the average level of stiffness during the last 7 days on an 11 point rating scale, ranging from 0-10 (0 = "no stiffness" and 10 = "severe stiffness"). A lower score indicates a lower severity.
Time Frame
Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo
Title
Level of physical function
Description
Assessed by the physical function domain of Fibromyalgia Impact Questionnaire Revised; asking participants to rate how difficult it is to perform a list of 9 common activities over the previous 7 days on an 11 point scale, ranging from 0-10 (0 = "no difficulty" and 10 = "very difficult"). The score is characterized by the sum of the 9 scores (0-90). A lower score indicates better function.
Time Frame
Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo
Title
Health-related quality of life - mobility
Description
Measured by the European Quality of Life 5 Dimensions (EQ-5D) mobility domain; asking the participants to rate their mobility on a 1-5 Verbal Rating Scale, a score of 1 indicating no problems, and a score of 5 indicating extreme problems. A lower score indicates a lower severity.
Time Frame
Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo
Title
Health-related quality of life - self care
Description
Measured by the European Quality of Life 5 Dimensions (EQ-5D) self care domain; asking the participants to rate their ability for self care on a 1-5 Verbal Rating Scale, a score of 1 indicating no problems, and a score of 5 indicating extreme problems. A lower score indicates a lower severity.
Time Frame
Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo
Title
Health-related quality of life - usual activities
Description
Measured by the European Quality of Life 5 Dimensions (EQ-5D) usual activities domain; asking the participants to rate their ability to perform usual activities on a 1-5 Verbal Rating Scale, a score of 1 indicating no problems, and a score of 5 indicating extreme problems. A lower score indicates a lower severity.
Time Frame
Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo
Title
Health-related quality of life - pain/discomfort
Description
Measured by the European Quality of Life 5 Dimensions (EQ-5D) pain/discomfort domain; asking the participants to rate their level of pain or discomfort on a 1-5 Verbal Rating Scale, a score of 1 indicating no problems, and a score of 5 indicating extreme problems. A lower score indicates a lower severity.
Time Frame
Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo
Title
Health-related quality of life - anxiety/depression
Description
Measured by the European Quality of Life 5 Dimensions (EQ-5D) anxiety/depression domain; asking the participants to rate their level of anxiety or depression on a 1-5 Verbal Rating Scale, a score of 1 indicating no problems, and a score of 5 indicating extreme problems. A lower score indicates a lower severity.
Time Frame
Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo
Title
Health-related quality of life - global
Description
Measured by European Quality of Life Visual Analogue Scale (EQ-VAS), which asks the participant to rate their overall health 'today' on a 0-100 VAS. A higher score indicates a better quality of life.
Time Frame
Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo
Title
Number of responders with a more than 15% improvement of pain
Description
A responder is defined as a subject who reports a more than 15% improvement of the primary outcome (average pain during the last 7 days) after 12 weeks of treatment with LDN or LDN-placebo. Number of responders are calculated for both the LDN group and the LDN-placebo group.
Time Frame
Number of responders after 12 weeks of treatment with LDN or LDN placebo
Title
Number of responders with a more than 30% improvement of pain
Description
A responder is defined as a subject who reports a more than 30% improvement of the primary outcome (average pain during the last 7 days) after 12 weeks of treatment with LDN or LDN-placebo. Number of responders are calculated for both the LDN group and the LDN-placebo group.
Time Frame
Number of responders after 12 weeks of treatment with LDN or LDN placebo
Title
Number of responders with a more than 50% improvement of pain
Description
A responder is defined as a subject who reports a more than 50% improvement of the primary outcome (average pain during the last 7 days) after 12 weeks of treatment with LDN or LDN-placebo. Number of responders are calculated for both the LDN group and the LDN-placebo group.
Time Frame
Number of responders after 12 weeks of treatment with LDN or LDN placebo
Other Pre-specified Outcome Measures:
Title
Variation in pain
Description
Measured using a diary of daily average pain rated on an 11 point rating scale, ranging from 0-10, during 7 days before visits at baseline, and after 8 and 12 weeks of treatment. The variation in pain is characterized by the highest score minus the lowest score. A lower score indicates a lower variation.
Time Frame
Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo
Title
Muscle exhaustion
Description
Measured by an isometric muscle exhaustion test of the deltoid muscle. Measured by asking the participant to complete an isometric muscle exhaustion task by maintaining 90° shoulder abduction (dominant arm) for as long as possible with the elbow extended and the hand pronated (hand facing downwards). Task failure (test position can no longer be maintained) defines the test duration. The participants are instructed to maintain the position until they feel maximal muscle exhaustion (corresponding to a score of 10 on a 0-10 scale with 0 being "no muscle fatigue" and 10 being 'maximal muscle fatigue/exhaustion'). Surface electromyography (EMG) will be recorded from the anterior, middle and posterior deltoid muscle at 3000 Hz during the entire test. A longer duration of test is indicative of lower levels of exhaustion.
Time Frame
Change from baseline when assessed after 12 weeks of treatment with LDN or LDN-placebo
Title
Physical fitness
Description
Measured by the 30-second chair stand test. The test starts with the subject seated on a chair with her back touching the backrest. Subjects rise to a full stand with the back straight and then sit down again to regain this cycle as many times as they can within 30 seconds. A higher number of cycles is indicative of better physical fitness.
Time Frame
Change from baseline when assessed after 12 weeks of treatment with LDN or LDN-placebo
Title
Pain sensitivity
Description
Assessments are conducted as recommended by the 'International Association for the Study of Pain'. Computer-controlled cuff algometry is performed on lower legs in all patients to assess pressure pain threshold and pressure pain tolerance. Pressure pain threshold and pressure pain tolerance are measured in kilopascal (kPa). A higher value is indicative of lower severity.
Time Frame
Change from baseline when assessed after 12 weeks of treatment with LDN or LDN-placebo
Title
Inhibition of pain
Description
Measured by Conditioned pain modulation (CPM). Assessments are conducted as recommended by the 'International Association for the Study of Pain'. Computer-controlled cuff algometry is performed on lower legs to assess increase in pressure pain threshold during cuff pain conditioning on the contralateral leg. Pressure pain threshold and pressure pain tolerance are measured in kilopascal (kPa). A higher value is indicative of lower severity.
Time Frame
Change from baseline when assessed after 12 weeks of treatment with LDN or LDN-placebo
Title
Augmentation of pain
Description
Measured by Temporal Summation of Pain (TSP). Assessments are conducted as recommended by the 'International Association for the Study of Pain'. Computer-controlled cuff algometry is performed on lower legs to assess increase in pain scores to ten repeated stimulations. Pain is rated on a 0-100 Visual Analogue Scale. A lower value indicates a lower severity.
Time Frame
Change from baseline when assessed after 12 weeks of treatment with LDN or LDN-placebo

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
64 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Women aged 18-64 years Understands and writes Danish Fulfills the American College of Rheumatology 1990 criteria for fibromyalgia A minimum score of 4 in self-reported average pain during the last 7 days on a 0-10 numeric rating scale at baseline All fertile women have to use safe anti conception (Spiral, birth control pills, contraceptive patch, contraceptive vaginal ring or gestagen injections) for 3 weeks before and 1 week after the trial. If the patients' normal lifestyle includes sexual abstinence, they do not have to use anti conception. Instead they can give an oral informed consent, that they will be sexually abstinent during the trial. A woman is considered non-fertile if she is sterilized, hysterectomized, bilateral oophorectomized or is postmenopausal. A woman is considered postmenopausal when vaginal bleeding has been absent for 1 year and is confirmed by measurement of follicle-stimulating hormone. Exclusion Criteria: Known allergy against naltrexonehydroclorid Pregnancy or breastfeeding. A negative pregnancy test has to be available for all fertile subjects at baseline Use of opioids or NSAIDs during the 4 weeks before inclusion in the trial Abuse of alcohol or other substances Inflammatory rheumatic diseases Demyelinating diseases Active cancer Liver dysfunction Kidney dysfunction Psychotic diseases History of suicide attempts Suicide ideation - evaluated using Patient Health Questionnaire-9 (Item 9 has to be answered "never")
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Karin D Bruun, Consultant
Organizational Affiliation
Odense University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Pain centre, Odense University Hospital
City
Odense
ZIP/Postal Code
5000
Country
Denmark

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
34781989
Citation
Bruun KD, Amris K, Vaegter HB, Blichfeldt-Eckhardt MR, Holsgaard-Larsen A, Christensen R, Toft P. Low-dose naltrexone for the treatment of fibromyalgia: protocol for a double-blind, randomized, placebo-controlled trial. Trials. 2021 Nov 15;22(1):804. doi: 10.1186/s13063-021-05776-7.
Results Reference
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Fibromyalgia and Naltrexone: The FINAL Study

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