Clinical trial NCT03300635: Metabolism, Muscle Function and Psychological Factors in Fibromyalgia
Official title: Metaboliset Muutokset ja Lihastoiminta Fibromyalgiassa
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Fibromyalgia
Lead sponsor: Helsinki University Central Hospital
Sponsor class: OTHER
Collaborators: name: University of Helsinki
First posted: 2017-10-03
Enrollment: 81
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: OTHER

Brief summary: 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

1. 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.
2. A glucose tolerance test, with other blood samples
3. 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.


Eligibility criteria: 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

Primary outcomes:
measure: metabolomics
timeFrame: up to day 3
measure: metabolomics (physical stress)
timeFrame: Day 3 (at the end of Exercise test)
measure: metabolomics (metabolic stress)
timeFrame: Day 2 ( at the end of Glucose test)
measure: muscle function (raw)
timeFrame: Day 1
measure: muscle function (normalized)
timeFrame: Day 1
measure: muscle rest time
timeFrame: Day 1
Secondary outcomes:
measure: Perceived distress during mental stress vs. relaxation (baseline)
timeFrame: Day 1 ( at the beginning of the recording during the Mental distress and relaxation test)
measure: Perceived distress during mental stress vs. relaxation (relaxation I)
timeFrame: Day 1 (after the first relaxation phase of the Mental distress and relaxation test)
measure: Perceived distress during mental stress vs. relaxation (mental stress I)
timeFrame: Day 1 (after the first mental stress phase of the Mental distress and relaxation test)
measure: Perceived distress during mental stress vs. relaxation (relaxation II)
timeFrame: Day 1 (after the second relaxation phase of the Mental distress and relaxation test)
measure: Perceived distress during mental stress vs. relaxation (mental stress II)
timeFrame: Day 1 (after the second mental stress phase of the Mental distress and relaxation test)
measure: Perceived distress during mental stress vs. relaxation (relaxation III)
timeFrame: Day 1 ( after the third relaxation phase of the Mental distress and relaxation test)
measure: Pain intensity during mental stress vs. relaxation (baseline)
timeFrame: Day 1 ( at the beginning of the recording during the Mental distress and relaxation test)
measure: Pain intensity during mental stress vs. relaxation (relaxation I)
timeFrame: Day 1 ( after the first relaxation phase of the Mental distress and relaxation test)
measure: Pain intensity during mental stress vs. relaxation (mental stress I)
timeFrame: Day 1 ( after the first mental stress phase of the Mental distress and relaxation test)
measure: Pain intensity during mental stress vs. relaxation (relaxation II)
timeFrame: Day 1 (after the second relaxation phase of the Mental distress and relaxation test)
measure: Pain intensity during mental stress vs. relaxation (mental stress II)
timeFrame: Day 1 (after the second mental stress phase of the Mental distress and relaxation test)
measure: Pain intensity during mental stress vs. relaxation (relaxation III)
timeFrame: Day 1 (after the third relaxation phase of the Mental distress and relaxation test)
measure: heart rate variability
timeFrame: Day 1
Other outcomes:
Locations:
city: Helsinki
country: Finland
facility: HelsinkiUCH
Study officials:
affiliation: Helsinki University Hospital and Helsinki University
name: Eija A Kalso, MD, PhD
role: STUDY_CHAIR
References:
citation: Zetterman T, Markkula R, Kalso E. Elevated highly sensitive C-reactive protein in fibromyalgia associates with symptom severity. Rheumatol Adv Pract. 2022 Jun 25;6(2):rkac053. doi: 10.1093/rap/rkac053. eCollection 2022.
citation: Zetterman T, Markkula R, Kalso E. Glucose tolerance in fibromyalgia. Medicine (Baltimore). 2021 Nov 19;100(46):e27803. doi: 10.1097/MD.0000000000027803.
citation: Zetterman T, Markkula R, Partanen JV, Miettinen T, Estlander AM, Kalso E. Muscle activity and acute stress in fibromyalgia. BMC Musculoskelet Disord. 2021 Feb 14;22(1):183. doi: 10.1186/s12891-021-04013-1.