E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated | |
E.1.1.1 | Medical condition in easily understood language | |
E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 | E.1.2 | Level | PT | E.1.2 | Classification code | 10048439 | E.1.2 | Term | Fibromyalgia | E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders | |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial | The aim of the trial is to investigate whether treatment with Low dose Naltrexone (LDN) has a superior effect compared with placebo on pain, tenderness and pain sensitivity in female patients with fibromyalgia, evaluated after 12 weeks of treatment. | |
E.2.2 | Secondary objectives of the trial | In the study we will also explore secondary aims regarding a possible improvement of early muscular exhaustion and physical fitness, a possible improvement of endogenous pain inhibition and a possible anti-inflammatory effect of LDN in FM patients. | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria | -Women aged 18-64 years -Understands and writes Danish -Fulfills the ACR1990 criteria for fibromyalgia -A minimum score of 4 in self-reported average pain during the last 7 days on a 0-10 NRS at baseline -All fertile women have to use safe anti conception | |
E.4 | Principal 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 up to 4 weeks before inclusion in the trial -Abuse of alcohol or other substances -Inflammatory rheumatic diseases -Demyelinating diseases -Active cancer -Liver dysfunction (ALAT must not be elevated more than 2-fold over highest reference level) -Kidney dysfunction (GFR < 59 mL/min) -Psychotic diseases -History of suicide attempts -Suicide ideation – evaluated using PHQ-9 (Item 9 has to be answered “never”) | |
E.5 End points |
E.5.1 | Primary end point(s) | Average pain during the last 7 days. Change from baseline when assessed after 12 weeks of treatment with LDN or LDN-placebo. 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. | |
E.5.1.1 | Timepoint(s) of evaluation of this end point | After 12 weeks of treatment | |
E.5.2 | Secondary end point(s) | Key secondary: - Global assessment. Change in overall fibromyalgia symptoms from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo. Measured by Patient Global Impression of Change on a 1-7 Verbal Rating Scale. - Impact of fibromyalgia. Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo. Measured by the Fibromyalgia Impact Questionnaire Revised (FIQR) total score. - Pain distribution. Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo. Assessed by the Widespread Pain Index (WPI) from The American College of Rheumatology 2016 revised criteria for fibromyalgia (ACR-2016). - Level of pain. Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo. 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 (0 = "no pain" and 10 = "unbearable pain") - Level of tenderness. Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo. 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 (0 = "no tenderness" and 10 = "very tender") 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. - Level of fatigue. Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo. 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 (0 = "lots of energy" and 10 = "no energy"). - Level of sleep disturbance. Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo. 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 (0 = "awoke well rested" and 10 = "awoke very tired"). - Level of depression. Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo. 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 (0 = "no depression" and 10 = "very depressed"). - Level of anxiety. Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo. 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 (0 = "not anxious" and 10 = "very anxious"). - Level of cognition. Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo. 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 (0 = "good memory" and 10 = "very poor memory"). - Level of stiffness. Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo. 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 (0 = "no stiffness" and 10 = "severe stiffness"). - Level of physical function. Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo. 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 (0 = "no difficulty" and 10 = "very difficult"). The score is characterized by the sum of the 9 scores (0-90). - Health-related quality of life. Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo. Measured by the European Quality of Life 5 Dimensions (EQ-5D) and the European Quality of Life VAS (EQ-VAS). The EQ-5D measures 5 domains including mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Every domain is rated on a 1-5 VRS, a score of 1 indicating no problems, and a score of 5 indicating extreme problems. The EQ-VAS asks the participant to rate their overall health ‘today’ on a 0-100 VAS. | |
E.5.2.1 | Timepoint(s) of evaluation of this end point | After 12 weeks of treatment | |
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 | The trial involves single site in the Member State concerned | Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 | Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial | Last visit - last subject | |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |