Investigation of Autonomic Dysfunction in Patients With Familial Mediterranean Fever

NCT05596643 | Unknown

• 1 other identifier: 09.2021.1427
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Familial Mediterranean Fever (FMF) is the most common inherited autoinflammatory disease affecting 150,000 patients worldwide. Periodic febrile exacerbations, peritonitis, and pleuritis are characteristic disease features. Dysregulation of IL-1β secretion has an important role in the pathophysiology of the disease, and IL-1β also serves as a therapeutic target. Chronic inflammation has been associated with early atherosclerotic and cardiovascular disease in various rheumatic diseases. An increased risk for cardiovascular events associated with disease activity has been described in rheumatoid arthritis, psoriatic arthritis, and systemic lupus erythematosus. In addition, autonomic nervous system dysfunction may contribute to increased cardiovascular risk in patients with inflammatory disease. For example, decreased heart rate variability is an important feature of cardiac autonomic dysfunction and is an isolated risk factor for cardiovascular events. Autonomic dysfunction studies related to FMF have conflicting results. The aim of this study was to determine autonomic dysfunction symptoms and objective findings in patients with FMF; Demographic characteristics, disease characteristics, inflammatory burden, fatigue level, sleep quality, presence of fibromyalgia and their relationship with quality of life were evaluated and compared with healthy controls.

Conditions

Familial Mediterranean Fever; Autonomic Dysfunction

Keywords

Familial Mediterranean Fever; Autonomic Dysfunction; r-r interval variability; sympathetic skin response

Outcome Measures

Primary Outcomes (8)

• Composite Autonomic Symptom Score-31

  It is a widely applicable, up-to-date, easy-to-apply and scientifically-based test that evaluates autonomic symptoms and functions by the person himself. It consists of 31 multiple-choice questions in 6 autonomic areas: orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder function and pupillomotor areas. A score in the range of 0-100 is obtained as a result of multiplying each area by the weight factor determined by the study. High score indicates presence and severity of autonomic dysfunction.

  6 months

• r-r interval variability with normal breathing

  The active and reference superficial recording electrodes are on the dorsal side of both hands, and the ground electrode is placed on the wrist. The R-R interval variability is calculated automatically by the electromyography device over a 1-minute recording.

  6 months

• r-r interval variability with deep breathing

  The active and reference superficial recording electrodes are on the dorsal side of both hands, and the ground electrode is placed on the wrist. In order to determine the R-R interval variability with deep breathing, the patient is given 6 to 8 deep breaths, consisting of 5 seconds of inspiration followed by 5 seconds of expiration, and the result is automatically calculated by the electromyography device.

  6 months

• Valsalva ratio

  The active and reference superficial recording electrodes are on the dorsal side of both hands, and the ground electrode is placed on the wrist. The test was performed by asking the subject to sit quietly and then blow into a mouthpiece attached to an aneroid pressure gauge at a pressure of 40 mmHg for 15 seconds. The ratio of the longest R-R interval shortly after the manoeuver (within about 20 beats) and the shortest R-R interval during the manoeuver is then measured. The result was expressed as the Valsalva ratio that is taken as the mean ratio from three successive Valsalva manoeuvers.

  6 months

• 30:15 ratio

  The active and reference superficial recording electrodes are on the dorsal side of both hands, and the ground electrode is placed on the wrist.The R-R interval on the ECG was recorded and used to determine the instantaneous HR at rest and then on the 15th and 30th beats after standing. The HR should normally rise after about 30 seconds as part of the response to return the blood pressure (BP) to normal. After standing up, the 30:15 ratio obtained by dividing the longest R-R distance around the 30th beat by the shortest R-R distance around the 15th beat was calculated automatically by the EMG device.

  6 months

• sympathetic skin response

  Sweating that occurs in response to many different stimuli, electrolyte in the skin triggers changes in skin conductivity, resulting in instantaneous changes in skin conductivity. Sympathetic skin response evaluates these instantaneous changes in the skin in response to sweating. Sympathetic skin response reflects the function of sympathetic nerve fibers.Active recording electrodes on palm and sole; reference electrodes is placed on the back of the hand and the back of the foot. Responses obtained by applying electrical current over the median nerve trace are evaluated.

  6 months

• blood pressure response to standing

  Participants were asked to stand up for 3 minutes after a 10-minute resting period in a supine position. The systolic and diastolic BP (SBP and DBP) just before standing, and 3 minutes after active standing were determined, in order to define postural change in BP and to evaluate orthostatic intolerance.

  6 months

• blood pressure response to sustained handgrip

  Blood pressure measurement is continued at 1-minute intervals while patients perform sustained handgip at 30% of their maximum volitional strength for 5 minutes.The absolute difference between the highest DBP during handgrip and the basal DBP just before the handgrip was noted.

  6 months

Secondary Outcomes (5)

• Familial Mediterranean Fever Quality of Life Scale (FMF-QoL)

  6 months

• Hospital Anxiety and Depression Scale (HADS)

  6 months

• Fibromyalgia Rapid Screening Tool (FIRST)

  6 months

• The Fatigue Severity Scale (FSS)

  6 months

• Jenkins Sleep Evaluation Scale (JSS)

  6 months

Study Arms (2)

Patients diagnosed with Familial Mediterranean Fever

Diagnostic Test: Composite Autonomic Symptom Score-31; Diagnostic Test: r-r interval variability with normal breathing; Diagnostic Test: r-r interval variability with deep breathing; Diagnostic Test: Valsalva ratio; Diagnostic Test: 30:15 ratio; Diagnostic Test: sympathetic skin response; Diagnostic Test: blood pressure response to standing; Diagnostic Test: blood pressure response to sustained handgrip test; Other: Hospital anxiety and depression scale; Diagnostic Test: Fibromyalgia rapid screening tool; Other: Familial Mediterranean Fever Quality of life scale; Other: Jenkins Sleep Evaluation Scale; Other: The Fatigue Severity Scale

Healthy Controls

Diagnostic Test: Composite Autonomic Symptom Score-31; Diagnostic Test: r-r interval variability with normal breathing; Diagnostic Test: r-r interval variability with deep breathing; Diagnostic Test: Valsalva ratio; Diagnostic Test: 30:15 ratio; Diagnostic Test: sympathetic skin response; Diagnostic Test: blood pressure response to standing; Diagnostic Test: blood pressure response to sustained handgrip test; Other: Hospital anxiety and depression scale; Diagnostic Test: Fibromyalgia rapid screening tool; Other: Jenkins Sleep Evaluation Scale; Other: The Fatigue Severity Scale

Interventions

Composite Autonomic Symptom Score-31 DIAGNOSTIC_TEST

Standardized questionnaire to determine the level of autonomic dysfunction

Also known as: COMPASS-31

Healthy Controls; Patients diagnosed with Familial Mediterranean Fever

r-r interval variability with normal breathing DIAGNOSTIC_TEST

electrophysiological test to detect parasympathetic dysfunction

Healthy Controls; Patients diagnosed with Familial Mediterranean Fever

r-r interval variability with deep breathing DIAGNOSTIC_TEST

electrophysiological test to detect parasympathetic dysfunction

Healthy Controls; Patients diagnosed with Familial Mediterranean Fever

Valsalva ratio DIAGNOSTIC_TEST

electrophysiological test to detect parasympathetic dysfunction

Healthy Controls; Patients diagnosed with Familial Mediterranean Fever

30:15 ratio DIAGNOSTIC_TEST

electrophysiological test to detect parasympathetic dysfunction

Healthy Controls; Patients diagnosed with Familial Mediterranean Fever

sympathetic skin response DIAGNOSTIC_TEST

electrophysiological test to detect sympathetic dysfunction

Also known as: SSR

Healthy Controls; Patients diagnosed with Familial Mediterranean Fever

blood pressure response to standing DIAGNOSTIC_TEST

clinical test to detect sympathetic dysfunction

Healthy Controls; Patients diagnosed with Familial Mediterranean Fever

blood pressure response to sustained handgrip test DIAGNOSTIC_TEST

clinical test to detect sympathetic dysfunction

Healthy Controls; Patients diagnosed with Familial Mediterranean Fever

Hospital anxiety and depression scale OTHER

Standardized questionnaire to investigate the depression and anxiety

Also known as: HADS

Healthy Controls; Patients diagnosed with Familial Mediterranean Fever

Fibromyalgia rapid screening tool DIAGNOSTIC_TEST

Standardized questionnaire to determine the presence of fibromyalgia

Also known as: FIRST

Healthy Controls; Patients diagnosed with Familial Mediterranean Fever

Familial Mediterranean Fever Quality of life scale OTHER

Standardized questionnaire to investigate the quality of life in Familial Mediterranean Fever patients

Also known as: FMFQoL

Patients diagnosed with Familial Mediterranean Fever

Jenkins Sleep Evaluation Scale OTHER

Standardized questionnaire to investigate the sleep quality and disturbance

Healthy Controls; Patients diagnosed with Familial Mediterranean Fever

The Fatigue Severity Scale OTHER

Standardized questionnaire to investigate the fatigue severity

Also known as: FSS

Healthy Controls; Patients diagnosed with Familial Mediterranean Fever

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with FMF Healthy control group

You may qualify if:

• Familial Mediterranean Fever group;
• Being between the ages of 18-65
• Having a definite diagnosis of Familial Mediterranean Fever according to Livneh criteria
• Healthy control group;
• Being between the ages of 18-65
• Absence of any disease diagnosis

You may not qualify if:

• Liver or kidney failure
• Pregnancy
• Diabetes mellitus
• Thyroid diseases
• Those who use neuroprotective or antihypertensive drugs
• Vitamin B12 deficiency
• Anemia
• Paraneoplastic neuropathy
• Alcoholism
• Cardiac failure
• Cardiac arrhythmia
• Acute thrombosis
• Having a diagnosis of another systemic rheumatic disease
• Persons who did not give consent to participate in the study

Sponsors & Collaborators

• Marmara University: lead

Study Sites (1)

Marmara University School of Medicine, Pendik Education and Research Hospital, Department of Physical Medicine and Rehabilitation

Istanbul, Turkey (Türkiye)

RECRUITING

MeSH Terms

Conditions

Familial Mediterranean Fever; Primary Dysautonomias

Interventions

4-amino-4'-hydroxylaminodiphenylsulfone

Condition Hierarchy (Ancestors)

Hereditary Autoinflammatory Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Autonomic Nervous System Diseases; Nervous System Diseases

Study Officials

• Mehmet Tuncay Duruöz, Prof

  Marmara University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

İmran Kalkan

CONTACT

+90 530 340 5594; imrankalkann55@gmail.com

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 24, 2022
• First Posted: October 27, 2022
• Study Start: March 15, 2022
• Primary Completion: October 31, 2022
• Study Completion: October 31, 2022
• Last Updated: October 27, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)