FibromyalgiaNCT05704374
The Effect of Sympathetic Dysfunction on Muscle Spindle in Fibromyalgia
A study testing sympathetic stimulation maneuver (mental arithmetic test, cold pressure test) and Pregabalin 150mg in people with Fibromyalgia, run by Istanbul Physical Medicine Rehabilitation Training and Research Hospital at 1 site in Turkey (Türkiye).
Trial summary
This study aims to reveal whether there is an impairment in the sympathetic regulation of muscle spindle sensitivity in patients with fibromyalgia syndrome (FMS). Read more about this study
- Who is it for?
- Ages 20 to 50 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Fibromyalgia
- What is being tested?
- sympathetic stimulation maneuver (mental arithmetic test, cold pressure test) and Pregabalin 150mg
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- 2 Nov 2023to 1 Dec 2023
- 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 20 to 50 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- For the fibromyalgia group
- Patients diagnosed with FMS based on the American college of rheumatology - 2016 criteria
- Between the ages of 20-50
- Being a woman
- Patients prescribed pregabalin for the treatment
- For the Healthy Control group
Show all 9Show fewer
- Between the ages of 20-50
- Being a woman
- Being healthy
Who cannot join
- Those with medical problems in the right upper and lower extremities (skin, neuromuscular, joint, vascular pathologies)
- Cases that cannot perform arithmetic operations
- Cold allergy
- Heart disease (arrhythmia, ischemic heart disease, heart failure)
- Hypertension
- Epilepsy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effect of Sympathetic Dysfunction on Muscle Spindle Activity in Patients With Fibromyalgia Syndrome
This study aims to reveal whether there is an impairment in the sympathetic regulation of muscle spindle sensitivity in patients with fibromyalgia syndrome (FMS).
Read the detailed description
The common muscle pain and fatigue symptoms of FMS can be explained by impaired sympathetic regulation of muscle spindle sensitivity. The aim of this study is to reveal whether there is an impairment in the sympathetic regulation of muscle spindle sensitivity in FMS patients.
Material method:
In the first stage, resting sympathetic tone measurement and resting H-reflex and T-reflex recordings will be taken in all cases. Sympathetic tone measurement will be performed and H-reflex and T-reflex recordings will be taken during and after sympathetic stimulation maneuvers (mental arithmetic calculation and cold application) in FMS patients and healthy control subjects. In the second phase, the first dose of pregabalin will be given to patients diagnosed with FMS and prescribed pregabalin. Pregabalin is known to reduce sympathetic activity in FMS. After oral administration of pregabalin, its peak plasma concentration is reached in 0.9-1.3 hours. Therefore, 1.5 hours later, sympathetic tone measurement will be made at rest and during the sympathetic stimulation maneuver, and H-reflex and T-reflex recordings will be taken. Patients in the healthy control group will not be given pregabalin.
- Conditions
- Fibromyalgia
- Being tested
- sympathetic stimulation maneuver (mental arithmetic test, cold pressure test), Pregabalin 150mg
- Keywords
- fibromyalgia
- Medical subject headings
- Fibromyalgia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sympathetic stimulation maneuver (mental arithmetic test, cold pressure test)Diagnostic test
Mental arithmetic calculation and cold pressure increase sympathetic tone. For the mental arithmetic task, the subject is asked to mentally subtract a two-digit number from a four-digit number and respond within 5 seconds. This arithmetic calculation is repeated for different numbers. This test is continued for three minutes. For the cold pressure test, subjects are asked to immerse their right hand in 2-4 degrees cold water up to the elbow and hold it in the water for three minutes. The mental arithmetic task and cold stress test will be applied simultaneously.
Pregabalin 150mgDrug
Also called sympathetic block
In the second phase of the experiment, 150 mg (single dose) of pregabalin will be given to FMS patients to reduce sympathetic activity and evaluate its effect on T- and H-reflexes.
| Study group | Role | What they receive |
|---|---|---|
| Fibromyalgia group | Experimental | In the first phase of the experiment, the effect of sympathetic tone change on T- and H-reflexes will be evaluated.
In the second phase of the experiment, 150 mg (single dose) of pregabalin will be given to these patients to reduce sympathetic activity and evaluate its effect on T- and H-reflexes. Receives: Diagnostic Test: sympathetic stimulation maneuver (mental arithmetic test, cold pressure test); Drug: Pregabalin 150mg |
| Healthy control group | Other | The effect of sympathetic tone changes on T- and H-reflexes will be evaluated in healthy cases. Receives: Diagnostic Test: sympathetic stimulation maneuver (mental arithmetic test, cold pressure test) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in T-reflex amplitude after intervention
In order to elicit the right soleus T-reflex, a constant-intensity strike will be made on the Achilles tendon with a reflex hammer at intervals of 10-15 seconds. An accelerometer will be placed over the Achilles tendon to measure T-reflex latency and confirm that strike intensities are constant. Recordings will be taken from the right soleus muscle. T-reflex peak-to-peak amplitudes will be measured in electromyographic recordings.
Measured: immediately after the intervention
Change from baseline in H-reflex amplitude after intervention
The right tibial nerve will be stimulated with a monopolar technique from the popliteal region to elicit the soleus H-reflex response. The stimulation electrode (cathode) will be placed on the tibial nerve in the popliteal fossa and the anode will be placed on the prepatellar region. For stimulation, a 1ms monophasic square wave pulse current will be given. Mmax will be determined firstly.The current intensity providing a 10% Mmax response will be used to test the H-reflex response. H-reflex peak-to-peak amplitude will be measured in electromyographic recordings.
Measured: immediately after the intervention
Secondary outcomes (1)
Heart rate variability
Sympathetic tone will be evaluated by measuring heart rate variability in the ECG recording taken from the DII lead.
Measured: immediately after the intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2023
- Study start2 Nov 2023 (estimated)
- Primary completion1 Dec 2023 (estimated)
- Study completion1 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for FibromyalgiaStudies of the same condition, open and under way.
- 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
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Istanbul Physical Medicine Rehabilitation Training and Research Hospital
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Tuğba Aydın, Istanbul Physical Medicine Rehabilitation Training and Research Hospital
- Investigators
- TUGBA AYDIN, Principal investigator, İstanbul Physical Therapy Rehabilitation Training & Research Hosptial
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05704374
- Sponsor's protocol ID
- IstanbulPMRTRH-Fibromyalgia
- Status last verified
- May 2023
- First submitted
- 7 Jan 2023
- Last updated
- 30 May 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Bair MJ, Krebs EE. Fibromyalgia. Ann Intern Med. 2020 Mar 3;172(5):ITC33-ITC48. doi: 10.7326/AITC202003030.
PubMed 32120395Aguilar-Ferrandiz ME, Casas-Barragan A, Tapia-Haro RM, Rus A, Molina F, Correa-Rodriguez M. Evaluation of sympathetic adrenergic branch of cutaneous neural control throughout thermography and its relationship to nitric oxide levels in patients with fibromyalgia. J Therm Biol. 2021 Jan;95:102813. doi: 10.1016/j.jtherbio.2020.102813. Epub 2020 Dec 14.
PubMed 33454042Reyes Del Paso GA, de la Coba P. Reduced activity, reactivity and functionality of the sympathetic nervous system in fibromyalgia: An electrodermal study. PLoS One. 2020 Oct 29;15(10):e0241154. doi: 10.1371/journal.pone.0241154. eCollection 2020.
PubMed 33119628Radovanovic D, Peikert K, Lindstrom M, Domellof FP. Sympathetic innervation of human muscle spindles. J Anat. 2015 Jun;226(6):542-8. doi: 10.1111/joa.12309.
PubMed 25994126Kamibayashi K, Nakazawa K, Ogata H, Obata H, Akai M, Shinohara M. Invariable H-reflex and sustained facilitation of stretch reflex with heightened sympathetic outflow. J Electromyogr Kinesiol. 2009 Dec;19(6):1053-60. doi: 10.1016/j.jelekin.2008.11.002. Epub 2008 Dec 19.
PubMed 19101166Hjortskov N, Skotte J, Hye-Knudsen C, Fallentin N. Sympathetic outflow enhances the stretch reflex response in the relaxed soleus muscle in humans. J Appl Physiol (1985). 2005 Apr;98(4):1366-70. doi: 10.1152/japplphysiol.00955.2004. Epub 2004 Nov 12.
PubMed 15542572Meeus M, Goubert D, De Backer F, Struyf F, Hermans L, Coppieters I, De Wandele I, Da Silva H, Calders P. Heart rate variability in patients with fibromyalgia and patients with chronic fatigue syndrome: a systematic review. Semin Arthritis Rheum. 2013 Oct;43(2):279-87. doi: 10.1016/j.semarthrit.2013.03.004. Epub 2013 Jul 6.
PubMed 23838093Light KC, Bragdon EE, Grewen KM, Brownley KA, Girdler SS, Maixner W. Adrenergic dysregulation and pain with and without acute beta-blockade in women with fibromyalgia and temporomandibular disorder. J Pain. 2009 May;10(5):542-52. doi: 10.1016/j.jpain.2008.12.006.
PubMed 19411061White AT, Light KC, Bateman L, Hughen RW, Vanhaitsma TA, Light AR. Effect of Pregabalin on Cardiovascular Responses to Exercise and Postexercise Pain and Fatigue in Fibromyalgia: A Randomized, Double-Blind, Crossover Pilot Study. Pain Res Treat. 2015;2015:136409. doi: 10.1155/2015/136409. Epub 2015 Dec 29.
PubMed 27026828Bockbrader HN, Radulovic LL, Posvar EL, Strand JC, Alvey CW, Busch JA, Randinitis EJ, Corrigan BW, Haig GM, Boyd RA, Wesche DL. Clinical pharmacokinetics of pregabalin in healthy volunteers. J Clin Pharmacol. 2010 Aug;50(8):941-50. doi: 10.1177/0091270009352087. Epub 2010 Feb 10.
PubMed 20147618
Study at a glance
From the registry record, last updated by the sponsor on 30 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Sympathetic Dysfunction on Muscle Spindle Activity in Patients With Fibromyalgia Syndrome
- ClinicalTrials.gov ID
- NCT05704374
- Acronym / sponsor ID
- IstanbulPMRTRH-Fibromyalgia
- Conditions
- Fibromyalgia
- Keywords
- fibromyalgia
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Istanbul Physical Medicine Rehabilitation Training and Research HospitalOther government
- Study start
- 2 Nov 2023 (estimated)
- Primary completion
- 1 Dec 2023 (estimated)
- Study completion
- 1 Dec 2023 (estimated)
- First posted
- 30 Jan 2023 (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.
This study aims to reveal whether there is an impairment in the sympathetic regulation of muscle spindle sensitivity in patients with fibromyalgia syndrome (FMS).
Detailed description
The common muscle pain and fatigue symptoms of FMS can be explained by impaired sympathetic regulation of muscle spindle sensitivity. The aim of this study is to reveal whether there is an impairment in the sympathetic regulation of muscle spindle sensitivity in FMS patients.
Material method:
In the first stage, resting sympathetic tone measurement and resting H-reflex and T-reflex recordings will be taken in all cases. Sympathetic tone measurement will be performed and H-reflex and T-reflex recordings will be taken during and after sympathetic stimulation maneuvers (mental arithmetic calculation and cold application) in FMS patients and healthy control subjects. In the second phase, the first dose of pregabalin will be given to patients diagnosed with FMS and prescribed pregabalin. Pregabalin is known to reduce sympathetic activity in FMS. After oral administration of pregabalin, its peak plasma concentration is reached in 0.9-1.3 hours. Therefore, 1.5 hours later, sympathetic tone measurement will be made at rest and during the sympathetic stimulation maneuver, and H-reflex and T-reflex recordings will be taken. Patients in the healthy control group will not be given pregabalin.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fibromyalgia group | Experimental | Diagnostic Test: sympathetic stimulation maneuver (mental arithmetic test, cold pressure test), Drug: Pregabalin 150mgIn the first phase of the experiment, the effect of sympathetic tone change on T- and H-reflexes will be evaluated. In the second phase of the experiment, 150 mg (single dose) of pregabalin will be given to these patients to reduce sympathetic activity and evaluate its effect on T- and H-reflexes. |
| Healthy control group | Other | Diagnostic Test: sympathetic stimulation maneuver (mental arithmetic test, cold pressure test)The effect of sympathetic tone changes on T- and H-reflexes will be evaluated in healthy cases. |
Who may qualify
- Ages
- 20 to 50 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- For the fibromyalgia group
- Patients diagnosed with FMS based on the American college of rheumatology - 2016 criteria
- Between the ages of 20-50
- Being a woman
- Patients prescribed pregabalin for the treatment
Key exclusion criteria (6 listed)
- Those with medical problems in the right upper and lower extremities (skin, neuromuscular, joint, vascular pathologies)
- Cases that cannot perform arithmetic operations
- Cold allergy
- Heart disease (arrhythmia, ischemic heart disease, heart failure)
- Hypertension
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 |
|---|---|---|
| sympathetic stimulation maneuver (mental arithmetic test, cold pressure test)Mental arithmetic calculation and cold pressure increase sympathetic tone. For the mental arithmetic task, the subject is asked to mentally subtract a two-digit number from a four-digit number and respond within 5 seconds. This arithmetic calculation is repeated for different numbers. This test is continued for three minutes. For the cold pressure test, subjects are asked to immerse their right hand in 2-4 degrees cold water up to the elbow and hold it in the water for three minutes. The mental arithmetic task and cold stress test will be applied simultaneously. | Diagnostic test | Fibromyalgia group, Healthy control group |
| Pregabalin 150mgAlso: sympathetic blockIn the second phase of the experiment, 150 mg (single dose) of pregabalin will be given to FMS patients to reduce sympathetic activity and evaluate its effect on T- and H-reflexes. | Drug | Fibromyalgia group |
Primary outcome
Change from baseline in T-reflex amplitude after intervention
Time frame: immediately after the intervention
In order to elicit the right soleus T-reflex, a constant-intensity strike will be made on the Achilles tendon with a reflex hammer at intervals of 10-15 seconds. An accelerometer will be placed over the Achilles tendon to measure T-reflex latency and confirm that strike intensities are constant. Recordings will be taken from the right soleus muscle. T-reflex peak-to-peak amplitudes will be measured in electromyographic recordings.
Change from baseline in H-reflex amplitude after intervention
Time frame: immediately after the intervention
The right tibial nerve will be stimulated with a monopolar technique from the popliteal region to elicit the soleus H-reflex response. The stimulation electrode (cathode) will be placed on the tibial nerve in the popliteal fossa and the anode will be placed on the prepatellar region. For stimulation, a 1ms monophasic square wave pulse current will be given. Mmax will be determined firstly.The current intensity providing a 10% Mmax response will be used to test the H-reflex response. H-reflex peak-to-peak amplitude will be measured in electromyographic recordings.
1 secondary outcome
Heart rate variability
Time frame: immediately after the intervention
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 May 2023.
- Background: PubMed 32120395Bair MJ, Krebs EE. Fibromyalgia. Ann Intern Med. 2020 Mar 3;172(5):ITC33-ITC48. doi: 10.7326/AITC202003030.
- Background: PubMed 33454042Aguilar-Ferrandiz ME, Casas-Barragan A, Tapia-Haro RM, Rus A, Molina F, Correa-Rodriguez M. Evaluation of sympathetic adrenergic branch of cutaneous neural control throughout thermography and its relationship to nitric oxide levels in patients with fibromyalgia. J Therm Biol. 2021 Jan;95:102813. doi: 10.1016/j.jtherbio.2020.102813. Epub 2020 Dec 14.
- Background: PubMed 33119628Reyes Del Paso GA, de la Coba P. Reduced activity, reactivity and functionality of the sympathetic nervous system in fibromyalgia: An electrodermal study. PLoS One. 2020 Oct 29;15(10):e0241154. doi: 10.1371/journal.pone.0241154. eCollection 2020.
- Background: PubMed 25994126Radovanovic D, Peikert K, Lindstrom M, Domellof FP. Sympathetic innervation of human muscle spindles. J Anat. 2015 Jun;226(6):542-8. doi: 10.1111/joa.12309.
- Background: PubMed 19101166Kamibayashi K, Nakazawa K, Ogata H, Obata H, Akai M, Shinohara M. Invariable H-reflex and sustained facilitation of stretch reflex with heightened sympathetic outflow. J Electromyogr Kinesiol. 2009 Dec;19(6):1053-60. doi: 10.1016/j.jelekin.2008.11.002. Epub 2008 Dec 19.
- Background: PubMed 15542572Hjortskov N, Skotte J, Hye-Knudsen C, Fallentin N. Sympathetic outflow enhances the stretch reflex response in the relaxed soleus muscle in humans. J Appl Physiol (1985). 2005 Apr;98(4):1366-70. doi: 10.1152/japplphysiol.00955.2004. Epub 2004 Nov 12.
- Background: PubMed 23838093Meeus M, Goubert D, De Backer F, Struyf F, Hermans L, Coppieters I, De Wandele I, Da Silva H, Calders P. Heart rate variability in patients with fibromyalgia and patients with chronic fatigue syndrome: a systematic review. Semin Arthritis Rheum. 2013 Oct;43(2):279-87. doi: 10.1016/j.semarthrit.2013.03.004. Epub 2013 Jul 6.
- Background: PubMed 19411061Light KC, Bragdon EE, Grewen KM, Brownley KA, Girdler SS, Maixner W. Adrenergic dysregulation and pain with and without acute beta-blockade in women with fibromyalgia and temporomandibular disorder. J Pain. 2009 May;10(5):542-52. doi: 10.1016/j.jpain.2008.12.006.
- Background: PubMed 27026828White AT, Light KC, Bateman L, Hughen RW, Vanhaitsma TA, Light AR. Effect of Pregabalin on Cardiovascular Responses to Exercise and Postexercise Pain and Fatigue in Fibromyalgia: A Randomized, Double-Blind, Crossover Pilot Study. Pain Res Treat. 2015;2015:136409. doi: 10.1155/2015/136409. Epub 2015 Dec 29.
- Background: PubMed 20147618Bockbrader HN, Radulovic LL, Posvar EL, Strand JC, Alvey CW, Busch JA, Randinitis EJ, Corrigan BW, Haig GM, Boyd RA, Wesche DL. Clinical pharmacokinetics of pregabalin in healthy volunteers. J Clin Pharmacol. 2010 Aug;50(8):941-50. doi: 10.1177/0091270009352087. Epub 2010 Feb 10.
- Individual participant dataSharing planned: No
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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.
TUGBA AYDIN principal investigator
İstanbul Physical Therapy Rehabilitation Training & Research Hosptial
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing sympathetic stimulation maneuver (mental arithmetic test, cold pressure test) and Pregabalin 150mg in people with Fibromyalgia, run by Istanbul Physical Medicine Rehabilitation Training and Research Hospital at 1 site in Turkey (Türkiye).
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 9 inclusion and 6 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: status not confirmed, as of the sponsor's last update on 30 May 2023. 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 Turkey (Türkiye). 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact TUGBA AYDIN, Assoc Prof (+905324622162, drtugbaaydin@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline in T-reflex amplitude after intervention (time frame: immediately after the intervention). The study lists 2 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 NCT05704374, which also lists 10 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 30 May 2023.