The Effect of Sympathetic Dysfunction on Muscle Spindle in Fibromyalgia

Fibromyalgia Clinical Trial

Official title:

The Effect of Sympathetic Dysfunction on Muscle Spindle Activity in Patients With Fibromyalgia Syndrome

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05704374
• Other study ID #: IstanbulPMRTRH-Fibromyalgia
• Status: Not yet recruiting
• Phase: N/A
• Start date: November 2, 2023
• Est. completion date: December 1, 2023

Study information

• Verified date: May 2023
• Source: Istanbul Physical Medicine Rehabilitation Training and Research Hospital
• Contact: TUGBA AYDIN, Assoc Prof
• Phone: +905324622162
• Email: drtugbaaydin[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical 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).

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 36
• Est. completion date: December 1, 2023
• Est. primary completion date: December 1, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 20 Years to 50 Years

Eligibility

Inclusion Criteria:

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

• Between the ages of 20-50

• Being a woman

• Being healthy

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Fibromyalgia
• Myofascial Pain Syndromes

Intervention

Diagnostic Test:
• 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.

Drug:
• Pregabalin 150mg
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.

Locations

Country	Name	City	State
Turkey	Tugba Aydin	Istanbul

Sponsors (1)

Lead Sponsor	Collaborator
Istanbul Physical Medicine Rehabilitation Training and Research Hospital

Country where clinical trial is conducted

Turkey, 

References & Publications (10)

Aguilar-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. — View Citation

Bair MJ, Krebs EE. Fibromyalgia. Ann Intern Med. 2020 Mar 3;172(5):ITC33-ITC48. doi: 10.7326/AITC202003030. — View Citation

Bockbrader 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. — View Citation

Hjortskov 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. — View Citation

Kamibayashi 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. — View Citation

Light 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. — View Citation

Meeus 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. — View Citation

Radovanovic 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. — View Citation

Reyes 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. Erratum In: PLoS One. 2020 Dec 28;15(12):e0244830. — View Citation

White 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	immediately after the intervention
Primary	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.	immediately after the intervention
Secondary	Heart rate variability	Sympathetic tone will be evaluated by measuring heart rate variability in the ECG recording taken from the DII lead.	immediately after the intervention