Metabolism, Muscle Function and Psychological Factors in Fibromyalgia

Metaboliset Muutokset ja Lihastoiminta Fibromyalgiassa

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.

Study Overview

• Status: Completed
• Conditions: Fibromyalgia
• Intervention / Treatment: Other: Exercise test; Other: Mental distress and relaxation test; Other: Glucose tolerance test

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Finland
  • Helsinki, Finland
    • HelsinkiUCH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Fibromyalgia patients; 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: Exercise test; Other: Mental distress and relaxation test; Other: Glucose tolerance test
Other: Healthy controls; 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: Exercise test; Other: Mental distress and relaxation test; Other: Glucose tolerance test

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Helsinki University Central Hospital
• Collaborators: University of Helsinki
• Investigators: Study Chair: Eija A Kalso, MD, PhD, Helsinki University Hospital and Helsinki University

Publications and helpful links

General Publications

• 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.
• Zetterman T, Markkula R, Kalso E. Glucose tolerance in fibromyalgia. Medicine (Baltimore). 2021 Nov 19;100(46):e27803. doi: 10.1097/MD.0000000000027803.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 5, 2015
• Primary Completion (Actual): April 10, 2019
• Study Completion (Actual): April 10, 2019

Study Registration Dates

• First Submitted: September 12, 2017
• First Submitted That Met QC Criteria: October 2, 2017
• First Posted (Actual): October 3, 2017

Study Record Updates

• Last Update Posted (Actual): December 13, 2019
• Last Update Submitted That Met QC Criteria: December 12, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Muscular Diseases; Neuromuscular Diseases; Fibromyalgia; Myofascial Pain Syndromes
• Other Study ID Numbers: TYH2017215

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data are available for only two of the researchers, Ritva Markkula and Teemu Zetterman, who are recruiting the subjects and collecting and coding their personal data to an unidentified mode.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No