FibromyalgiaNCT03300635
Metabolism, Muscle Function and Psychological Factors in Fibromyalgia
A study testing Mental distress and relaxation test, Glucose tolerance test and Exercise test in people with Fibromyalgia, run by Helsinki University Central Hospital at 1 site in Finland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Fibromyalgia
- What is being tested?
- Mental distress and relaxation test, Glucose tolerance test and Exercise test
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 81 participants
- Where
- 1 siteFinland
- Study dates
- 5 Sep 2015to 10 Apr 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- fibromyalgia diagnosed by the researchers RM or TZ, based on the ACR criteria from 1990
- Finnish as native language
Who cannot join
- male sex
- muscular or neuromuscular diseases
- diabetes
- heart disease
- generalised atherosclerosis
- untreated hypertension
Show all 9Show fewer
- neurological or other disease that systematically affects muscles
- a severe psychiatric disorder
- regular consumption of beta-blockers, bronchodilators, or statins
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read more
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.
- Conditions
- Fibromyalgia
- Being tested
- Mental distress and relaxation test, Glucose tolerance test, Exercise test
- Medical subject headings
- Fibromyalgia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mental distress and relaxation testOther
Glucose tolerance testOther
Exercise testOther
| Study group | Role | What they receive |
|---|---|---|
| Fibromyalgia patients | Other | All study subjects, both patients and healthy controls, will attend all three interventions: Mental distress and relaxation test, Glucose tolerance test, and Exercise test Receives: Other: Mental distress and relaxation test; Other: Glucose tolerance test; Other: Exercise test |
| Healthy controls | Other | All study subjects, both patients and healthy controls, will attend all three interventions: Mental distress and relaxation test, Glucose tolerance test, and Exercise test Receives: Other: Mental distress and relaxation test; Other: Glucose tolerance test; Other: Exercise test |
What is being measured
The primary outcome is the main question the study is designed to answer.
metabolomics
the difference of value distribution in metabolics panel between groups
Measured: up to day 3
metabolomics (physical stress)
the difference of value distribution in metabolics panel between groups
Measured: Day 3 (at the end of Exercise test)
metabolomics (metabolic stress)
the difference of value distribution in metabolics panel between groups
Measured: Day 2 ( at the end of Glucose test)
muscle function (raw)
sEMG signal amplitude
Measured: Day 1
muscle function (normalized)
normalized signal amplitude (%sEMGmax)
Measured: Day 1
muscle rest time
time of sEMG signal amplitude < 0.5% sEMGmax
Measured: Day 1
Secondary outcomes (13)
Perceived distress during mental stress vs. relaxation (baseline)
reported distress intensity (NRS)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2017
- Study start5 Sep 2015
- Primary completion10 Apr 2019
- Study completion10 Apr 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for FibromyalgiaStudies of the same condition, open and under way.
- More trials run by Helsinki University Central HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- 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 blind
- Who is masked
- Outcomes assessor
- Enrolment
- 81 participants (actual)
Sponsor and investigators
- Lead sponsor
- Helsinki University Central Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- University of Helsinki
- Responsible party
- Principal investigator, Ritva Markkula, Helsinki University Central Hospital
- Investigators
- Eija A Kalso, MD, PhD, Study chair, Helsinki University Hospital and Helsinki University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03300635
- Sponsor's protocol ID
- TYH2017215
- Status last verified
- Dec 2019
- First submitted
- 12 Sep 2017
- Last updated
- 13 Dec 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
Lehto T, Zetterman T, Gagnon D, Markkula R, Arokoski J, Kalso E, Peltonen JE. Muscle and cerebral oxygenation during exercise in fibromyalgia: a near-infrared spectroscopy study. Eur J Appl Physiol. 2026 Mar;126(3):1723-1735. doi: 10.1007/s00421-025-06013-8. Epub 2025 Oct 9.
PubMed 41065862Lehto T, Zetterman T, Markkula R, Arokoski J, Tikkanen H, Kalso E, Peltonen JE. Cardiac output and arteriovenous oxygen difference contribute to lower peak oxygen uptake in patients with fibromyalgia. BMC Musculoskelet Disord. 2023 Jul 1;24(1):541. doi: 10.1186/s12891-023-06589-2.
PubMed 37393269Zetterman T, Markkula R, Miettinen T, Kalso E. Heart rate variability responses to cognitive stress in fibromyalgia are characterised by inadequate autonomous system stress responses: a clinical trial. Sci Rep. 2023 Jan 13;13(1):700. doi: 10.1038/s41598-023-27581-9.
PubMed 36639565Zetterman 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.
PubMed 35832286Zetterman T, Markkula R, Kalso E. Glucose tolerance in fibromyalgia. Medicine (Baltimore). 2021 Nov 19;100(46):e27803. doi: 10.1097/MD.0000000000027803.
PubMed 34797307Zetterman 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.
PubMed 33583408
Study at a glance
From the registry record, last updated by the sponsor on 13 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metaboliset Muutokset ja Lihastoiminta Fibromyalgiassa
- ClinicalTrials.gov ID
- NCT03300635
- Acronym / sponsor ID
- TYH2017215
- Conditions
- Fibromyalgia
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 81 participants (actual)
- Lead sponsor
- Helsinki University Central HospitalUniversity, hospital or other
- Collaborators
- University of Helsinki
- Study start
- 5 Sep 2015 (actual)
- Primary completion
- 10 Apr 2019 (actual)
- Study completion
- 10 Apr 2019 (actual)
- First posted
- 3 Oct 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Fibromyalgia patients | Other | Other: Mental distress and relaxation test, Other: Glucose tolerance test, Other: Exercise testAll study subjects, both patients and healthy controls, will attend all three interventions: Mental distress and relaxation test, Glucose tolerance test, and Exercise test |
| Healthy controls | Other | Other: Mental distress and relaxation test, Other: Glucose tolerance test, Other: Exercise testAll study subjects, both patients and healthy controls, will attend all three interventions: Mental distress and relaxation test, Glucose tolerance test, and Exercise test |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- fibromyalgia diagnosed by the researchers RM or TZ, based on the ACR criteria from 1990
- Finnish as native language
Key exclusion criteria (9 listed)
- male sex
- muscular or neuromuscular diseases
- diabetes
- heart disease
- generalised atherosclerosis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mental distress and relaxation test | Other | Fibromyalgia patients, Healthy controls |
| Glucose tolerance test | Other | Fibromyalgia patients, Healthy controls |
| Exercise test | Other | Fibromyalgia patients, Healthy controls |
Primary outcome
metabolomics
Time frame: up to day 3
the difference of value distribution in metabolics panel between groups
metabolomics (physical stress)
Time frame: Day 3 (at the end of Exercise test)
the difference of value distribution in metabolics panel between groups
metabolomics (metabolic stress)
Time frame: Day 2 ( at the end of Glucose test)
the difference of value distribution in metabolics panel between groups
muscle function (raw)
Time frame: Day 1
sEMG signal amplitude
muscle function (normalized)
Time frame: Day 1
normalized signal amplitude (%sEMGmax)
muscle rest time
Time frame: Day 1
time of sEMG signal amplitude < 0.5% sEMGmax
13 secondary outcomes
Perceived distress during mental stress vs. relaxation (baseline)
Time frame: Day 1 ( at the beginning of the recording during the Mental distress and relaxation test)
Perceived distress during mental stress vs. relaxation (relaxation I)
Time frame: Day 1 (after the first relaxation phase of the Mental distress and relaxation test)
Perceived distress during mental stress vs. relaxation (mental stress I)
Time frame: Day 1 (after the first mental stress phase of the Mental distress and relaxation test)
Perceived distress during mental stress vs. relaxation (relaxation II)
Time frame: Day 1 (after the second relaxation phase of the Mental distress and relaxation test)
Perceived distress during mental stress vs. relaxation (mental stress II)
Time frame: Day 1 (after the second mental stress phase of the Mental distress and relaxation test)
Perceived distress during mental stress vs. relaxation (relaxation III)
Time frame: Day 1 ( after the third relaxation phase of the Mental distress and relaxation test)
Pain intensity during mental stress vs. relaxation (baseline)
Time frame: Day 1 ( at the beginning of the recording during the Mental distress and relaxation test)
Pain intensity during mental stress vs. relaxation (relaxation I)
Time frame: Day 1 ( after the first relaxation phase of the Mental distress and relaxation test)
Pain intensity during mental stress vs. relaxation (mental stress I)
Time frame: Day 1 ( after the first mental stress phase of the Mental distress and relaxation test)
Pain intensity during mental stress vs. relaxation (relaxation II)
Time frame: Day 1 (after the second relaxation phase of the Mental distress and relaxation test)
Pain intensity during mental stress vs. relaxation (mental stress II)
Time frame: Day 1 (after the second mental stress phase of the Mental distress and relaxation test)
Pain intensity during mental stress vs. relaxation (relaxation III)
Time frame: Day 1 (after the third relaxation phase of the Mental distress and relaxation test)
heart rate variability
Time frame: Day 1
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Dec 2019.
- Derived from this study: PubMed 41065862Lehto T, Zetterman T, Gagnon D, Markkula R, Arokoski J, Kalso E, Peltonen JE. Muscle and cerebral oxygenation during exercise in fibromyalgia: a near-infrared spectroscopy study. Eur J Appl Physiol. 2026 Mar;126(3):1723-1735. doi: 10.1007/s00421-025-06013-8. Epub 2025 Oct 9.
- Derived from this study: PubMed 37393269Lehto T, Zetterman T, Markkula R, Arokoski J, Tikkanen H, Kalso E, Peltonen JE. Cardiac output and arteriovenous oxygen difference contribute to lower peak oxygen uptake in patients with fibromyalgia. BMC Musculoskelet Disord. 2023 Jul 1;24(1):541. doi: 10.1186/s12891-023-06589-2.
- Derived from this study: PubMed 36639565Zetterman T, Markkula R, Miettinen T, Kalso E. Heart rate variability responses to cognitive stress in fibromyalgia are characterised by inadequate autonomous system stress responses: a clinical trial. Sci Rep. 2023 Jan 13;13(1):700. doi: 10.1038/s41598-023-27581-9.
- Derived from this study: PubMed 35832286Zetterman 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.
- Derived from this study: PubMed 34797307Zetterman T, Markkula R, Kalso E. Glucose tolerance in fibromyalgia. Medicine (Baltimore). 2021 Nov 19;100(46):e27803. doi: 10.1097/MD.0000000000027803.
- Derived from this study: PubMed 33583408Zetterman 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.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eija A Kalso, MD, PhD study chair
Helsinki University Hospital and Helsinki University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Mental distress and relaxation test, Glucose tolerance test and Exercise test in people with Fibromyalgia, run by Helsinki University Central Hospital at 1 site in Finland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Finland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
metabolomics (time frame: up to day 3). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03300635, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Dec 2019.