Metabolism, Muscle Function and Psychological Factors in Fibromyalgia

Study Overview
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Brief Summary
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Fibromyalgia (FM) is a world widely common syndrome, characterized by widespread pain, often accompanied by general fatigue, soreness, and abnormal sensations (like pins and needles). The reasons and the mechanisms (pathogenesis) of FM are still poorly understood. Efficacious therapies cannot be developed without understanding the pathophysiological mechanisms of the disease or syndrome. FM patients suffer from pain and sense of weakness and fatigue in the muscles, and often report difficulty in relaxing their muscles. So far, the studies on muscle activation in fibromyalgia (mostly using surface electromyography) have shown some unusual functioning, a kind of overuse, but the results have been somewhat contradictory. FM symptoms share some features with small fibre neuropathy, which is a disease or abnormality of small nerve fibres with a diverse aetiology. Recently, several research groups have shown (studying both the electrical function of superficial nerves and nerve endings of skin samples) that up to 50% of the FM patients with severe symptoms have small fibre neuropathy: their small nerves do not function properly and small nerve fibre density in their skin is reduced. However, as this phenomenon is common but not a rule, it might be rather a consequence of some underlying mechanisms of the syndrome, creating even more symptoms. The aim is to investigate whether there would exist metabolic changes in FM patients that would create pain and lead to functional changes and damage in small nerve fibres. The investigators also aim to explore the muscle function particularly in distressed situations and at rest. The hypothesis is that a towards-overuse-altered function would create unfavourable metabolic changes. Third, the aim is to investigate some psychological factors (such as tendency to get anxious or distressed) to find out, if there is any association between them and muscle function. The FM patients as well as healthy control subjects will be recruited at Helsinki University Hospital Pain Clinic and from primary care at Vantaa Health Care Centre. The voluntary test subjects will attend A muscle function examination of 30 minutes with electromyography using surface electrodes, including mentally distressing tasks and relaxing periods. At the same session, the subject will reply to some questionnaires regarding their symptoms and measuring some psychological factors. Actual pain level will be assessed. A glucose tolerance test, with other blood samples A bicycle ergometer exercise test of 20 - 30 minutes, with both physiological and chemical (blood samples) recordings. Actual pain level will be assessed as well. At this stage, 40 patients and 20 healthy control subjects will be recruited.

Official Title
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Metaboliset Muutokset ja Lihastoiminta Fibromyalgiassa

Conditions
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Fibromyalgia

Intervention / Treatment
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* Other: Mental distress and relaxation test
* Other: Glucose tolerance test
* Other: Exercise test


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: fibromyalgia diagnosed by the researchers RM or TZ, based on the ACR criteria from 1990 Finnish as native language Exclusion Criteria: male sex muscular or neuromuscular diseases diabetes heart disease generalised atherosclerosis untreated hypertension neurological or other disease that systematically affects muscles a severe psychiatric disorder regular consumption of beta-blockers, bronchodilators, or statins

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients and healthy control subjects will attend the same interventions: a) muscle function test (distressing task vs. relaxing) with e.g. psychological questionnaires, b) glucose tolerance test and other blood analyses including metabolomics, and c) bicycle ergometry with physiological measurements and blood analyses including metabolomics.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Fibromyalgia patients<br>All study subjects, both patients and healthy controls, will attend all three interventions: Mental distress and relaxation test, Glucose tolerance test, and Exercise test | Other: Mental distress and relaxation test<br> <br> Other: Glucose tolerance test<br> <br> Other: Exercise test<br> <br> |
| Other: Healthy controls<br>All study subjects, both patients and healthy controls, will attend all three interventions: Mental distress and relaxation test, Glucose tolerance test, and Exercise test | Other: Mental distress and relaxation test<br> <br> Other: Glucose tolerance test<br> <br> Other: Exercise test<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| metabolomics | the difference of value distribution in metabolics panel between groups | up to day 3 | 
| metabolomics (physical stress) | the difference of value distribution in metabolics panel between groups | Day 3 (at the end of Exercise test) | 
| metabolomics (metabolic stress) | the difference of value distribution in metabolics panel between groups | Day 2 ( at the end of Glucose test) | 
| muscle function (raw) | sEMG signal amplitude | Day 1 | 
| muscle function (normalized) | normalized signal amplitude (%sEMGmax) | Day 1 | 
| muscle rest time | time of sEMG signal amplitude < 0.5% sEMGmax | Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Perceived distress during mental stress vs. relaxation (baseline) | reported distress intensity (NRS) | Day 1 ( at the beginning of the recording during the Mental distress and relaxation test) | 
| Perceived distress during mental stress vs. relaxation (relaxation I) | reported distress intensity (NRS) | Day 1 (after the first relaxation phase of the Mental distress and relaxation test) | 
| Perceived distress during mental stress vs. relaxation (mental stress I) | reported distress intensity (NRS) | Day 1 (after the first mental stress phase of the Mental distress and relaxation test) | 
| Perceived distress during mental stress vs. relaxation (relaxation II) | reported distress intensity (NRS) | Day 1 (after the second relaxation phase of the Mental distress and relaxation test) | 
| Perceived distress during mental stress vs. relaxation (mental stress II) | reported distress intensity (NRS) | Day 1 (after the second mental stress phase of the Mental distress and relaxation test) | 
| Perceived distress during mental stress vs. relaxation (relaxation III) | reported distress intensity (NRS) | Day 1 ( after the third relaxation phase of the Mental distress and relaxation test) | 
| Pain intensity during mental stress vs. relaxation (baseline) | reported pain intensity (NRS) | Day 1 ( at the beginning of the recording during the Mental distress and relaxation test) | 
| Pain intensity during mental stress vs. relaxation (relaxation I) | reported pain intensity (NRS) | Day 1 ( after the first relaxation phase of the Mental distress and relaxation test) | 
| Pain intensity during mental stress vs. relaxation (mental stress I) | reported pain intensity (NRS) | Day 1 ( after the first mental stress phase of the Mental distress and relaxation test) | 
| Pain intensity during mental stress vs. relaxation (relaxation II) | reported pain intensity (NRS) | Day 1 (after the second relaxation phase of the Mental distress and relaxation test) | 
| Pain intensity during mental stress vs. relaxation (mental stress II) | reported pain intensity (NRS) | Day 1 (after the second mental stress phase of the Mental distress and relaxation test) | 
| Pain intensity during mental stress vs. relaxation (relaxation III) | reported pain intensity (NRS) | Day 1 (after the third relaxation phase of the Mental distress and relaxation test) | 
| heart rate variability | variability of heart beat interval evaluated as root mean square successive difference (RMSSD) | Day 1 |