Back to resultsFIbromyalgia anD GenetIcs Subgroups (FIDGIS) (FIDGIS)
Primary Purpose
Fibromyalgia
Status
Completed
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Electrophysiological measurement of reflex nociceptive flexion threshold (RIII reflex) using Nicolet Vicking device
Sponsored by
About this trial
This is an interventional basic science trial for Fibromyalgia focused on measuring Fibromyalgia syndrome, Chronic pain, Widespread pain, genetics, central sensitization
Eligibility Criteria
Patient Inclusion criteria :
- Patient between 18 and 65 years old (included),
- Patient with fibromyalgia according to the criteria of the 2016 ACR,
- Patient weighing more than 45kg
- Cooperation and understanding sufficient to comply with the requirements of the study,
- Acceptance to give written consent,
- Affiliation to the French Social Security system,
Patient exclusion criteria :
- treated with antibiotics in the three months prior to inclusion,
- who has reported gastroenteritis in the two months prior to inclusion,
- having a medical and / or surgical history judged by the investigator or his representative to be incompatible with the test
- of childbearing age not using an effective contraceptive method, pregnant or breastfeeding woman.
- participating in another clinical trial, or being in the exclusion period, or having received a total amount of benefits exceeding EUR 4500 over the 12 months preceding the start of the trial,
- benefiting from a measure of legal protection (guardianship, guardianship, deprivation of liberty, safeguard of justice),
Subject inclusion criteria:
- Aged of more than 18 years,
- weighing more than 45kg
- non-painful subjects matched by age (+/- 5 years), by sex, and by menopausal status for women,
- Cooperation and understanding sufficient to comply with the requirements of the study,
- Acceptance of written consent,
- Affiliation to the French Social Security system,
- Registration or acceptance of registration in the National Register of Volunteers participating in research.
Subject exclusion criteria :
- treated with antibiotics in the three months prior to inclusion,
- who has reported gastroenteritis in the two months prior to inclusion,
- Medical and / or surgical history judged by the investigator or his representative to be incompatible with the test,
- Intake of any drugs in the 7 days before inclusion,
- Pregnant or nursing woman
- Participating in another clinical trial, or within the exclusion period, or having received a total amount of compensation in excess of EUR 4500 over the 12 months preceding the start of the trial,
- Benefiting from a measure of legal protection (curatorship, guardianship, safeguard of justice ...)
Sites / Locations
- CHU de Clermont-Ferrand
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Sham Comparator
Arm Label
Patient with fibromyalgia syndrome
Healthy subjects
Arm Description
250 patients with fibromyalgia syndrome (according to American College of Rheumatology 2016) will realize explorations to characterize central sensitization: reflex nociceptive flexion threshold by electrophysiological measure and blood sampling for evaluate the distribution of gene polymorphism.
50 healthy matched volunteers (age, sex and menopausal status for women) will realize explorations to characterize central sensitization: reflex nociceptive flexion threshold by electrophysiological measure and blood sampling for evaluate distribution of gene polymorphism
Outcomes
Primary Outcome Measures
Evaluation of nociception flexion reflex (RIII) threshold by electromyography
Patient rested comfortably in a supine position in order to obtain muscular relaxation. Cutaneous electrodes will be applied, and the sural nerve will be stimulated in its retromaleolar track. Electromyographic responses will recorded using the Nicolet Vicking device with a pair of surface electrodes placed over the tendon of the ipsilateral biceps femoris.
The R-III reflex (objective threshold) will be identified as a multiphasic signal appearing at least 90 ms but less than 250 ms after each stimulation and will be considered to be present when the corrected computed surface was >0.5 mV/ms (positive response).
Secondary Outcome Measures
Evaluation of genetic polymorphism using OpenArray technology
Genome-wide association studies highlight that genetic factors are possibly responsible for up to 50% of the disease susceptibility, and several potential candidate genes have been found to be associated to fibromyalgia, including catecholaminergic (COMT), serotoninergic (HTR2A, SLC6A4), dopaminergic (GCH1, TAAR1) and glutamatergic (GRIA4) pathways. The participants will be genotyped for selected SNPs (120 SNPs- OpenArray technology) that have been previously investigated in relation to FM susceptibility, symptoms or potential mechanisms (Algynomics and international publications).
A single blood sample will be obtained on visit 1 day 1 and 4 aliquotes will be frozen at -80°C and kept frozen until the Open Array Technology analysis
Evaluation of central sensitization
assessed by Central Sensitization Inventory questionnaire
Mechanical temporal summation by numerical scale (0 to 10)
The mechanical temporal summation test will be performed using a 180g (Size 6.45) Von Frey filament applied to the non-dominant arm of the patient/subject who are sitting comfortably in a quiet room. The Von Frey filament will be applied against the skin of the participant at right angle, the manipulator performs a pressure movement until the filament flexes slightly. The participant scores on a numerical verbal scale (0 to 10) the intensity of pain perceived by the application of a single stimulus, and then of ten stimuli
Concise Pain Questionnaire (QCD)
This self-assessment scale allows the patient to characterize the pain in relation to its psychosocial intensity and impact. The patient is asked to answer 9 graduated questions by circling a number from 0 (no pain) to 10 (the most horrible pain you can imagine). Among these questions the patient is asked to blacken the painful areas on a diagram and to put an S if the pain is on the surface or a P if it is deep
Detection of fibromyalgia using the FIRST questionnaire
The FIRST questionnaire is a 6-item self-questionnaire that detects fibromyalgia. The patient is asked to answer "yes" or "no". Five "yes" allow to detect fibromyalgia when pain has persisted for more than 3 months
Evaluation of the impact of fibromyalgia using the FIQ questionnaire
The revised FIQ questionnaire is a 10-item self-questionnaire that assesses the impact of fibromyalgia. The first item is subdivided into 10 questions that assess the impact of the disease in everyday life
Evaluation of the Suspended Symmetrical Dorsal Cellulalgia
The experimenter makes a palpate-roll (by slightly lifting the skin) between the thumb and the other 4 fingers of the hand by following an axis on each side of the patient's spine. The palpate roll begins at the lumbar level and rises to the level of the shoulder blades on each side of the spine. The test is performed on one side of the spine and then on the other. The palpate roll should be performed 5 times on each side of the spine alternately. The investigator should rate for each side and at each pass whether the patient is experiencing pain or not. If the patient does not feel pain after 5 passes, the test is considered negative.
Quality of life by SF-36 quality of life questionnaire
the quality of life of the participants will be assessed by the self-administrated General Questionnaire 36-Item Short Form Survey (SF-36). The SF-36 questionnaire consists of 36 items and assesses an individual's physical and mental health using eleven questions related to eight aspects of health: physical function, role physical, bodily pain, general health, vitality, social function, role emotional, mental health.Global score ranges from 0 to 100.
Emotional status by Hospital Anxiety and Depression scale (HAD)
The Hospital Anxiety and Depression scale is a self-administered questionnaire in 14 items completed by the participant. It is used to determine the levels of anxiety and depression. Seven of the items relate to anxiety and seven relate to depression. Global score ranges from 0 to 42.
Evaluation of micro ARN using OpenArray technology
Studies have shown that thousands of human protein coding genes are regulated by micro RNAs, indicating that micro RNAs are "master regulators" of many important biological processes and some of this microRNA can be implicated in fibromyalgia continuum. The participants micro RNA's will be analyzed for 754 human selected micro RNA (OpenArray technology) that have been previously investigated in relation to FM susceptibility, symptoms or potential mechanisms. A single blood sample will be obtained on visit 1 day 1 and 6 aliquotes will be frozen at -80°C and kept frozen until the Open Array Technology analysis.
Analysis of the microbiota (stool samples),
Identification of bacterial biodiversity by a genetic sequencing analysis of bacterial DNA. The stool samples will be collected and then frozen at -80°C and kept frozen until analysis.
Evaluation of sensitivity to pain by PSQ questionnaire
the sensitivity to pain of the participants will be assessed by the Pain Sensitivity Questionnaire (PSQ). The PSQ questionnaire explore natural sensitivity to pain using questions simulating more or less intense pain situation using 17 questions.
Evaluation of sensitivity to sound by audiometer
the uncomfortable loudness level (ULL) of the participants will be assessed using the procedure of the British audiology society using a conventional audiometer (pure sound emission). The ULL is the level at which the participant responds or clearly feels uncomfortable and confirms this fact after removing the helmet.
Evaluation of sensitivity to light by led panel
the light sensitivity level of the participants will be assessed using a led panel (Lykos Daylight, Manfrotto) in a room without any source of natural light. The light intensity will be progressive (by step of 1 seconds flash light every 20 seconds) and the participant will stop the test when the intensity of the light will be uncomfortable. The light sensitivity is the level at which the participant feels uncomfortable
Full Information
NCT ID
NCT04624581
First Posted
November 5, 2020
Last Updated
June 7, 2022
Sponsor
University Hospital, Clermont-Ferrand
Collaborators
Service de pharmacologie et toxicologie cliniques, Hôpitaux Universitaire Genève, Rue Gabrielle Perret-Gentil 4, 1205 Genève, SUISSE, Association des Fibromyalgiques d'Auvergne, 19 Place de la Résistance, 63800 Cournon d'Auvergne, FRANCE
1. Study Identification
Unique Protocol Identification Number
NCT04624581
Brief Title
FIbromyalgia anD GenetIcs Subgroups (FIDGIS)
Acronym
FIDGIS
Official Title
Genetic Characteristics and Determinants of Central Sensitization of Nociception in Fibromylagic Syndrome
Study Type
Interventional
2. Study Status
Record Verification Date
December 2020
Overall Recruitment Status
Completed
Study Start Date
November 30, 2020 (Actual)
Primary Completion Date
January 17, 2022 (Actual)
Study Completion Date
January 17, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Clermont-Ferrand
Collaborators
Service de pharmacologie et toxicologie cliniques, Hôpitaux Universitaire Genève, Rue Gabrielle Perret-Gentil 4, 1205 Genève, SUISSE, Association des Fibromyalgiques d'Auvergne, 19 Place de la Résistance, 63800 Cournon d'Auvergne, FRANCE
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Fibromyalgia syndrome (FS) is characterized by widespread pain and affect 0.5 to 5 % of the general population, with a higher prevalence in women. Recognized as disease by World Health Organization since 1992, FS concern 1.2 to 2 million of French people and his etiology need to be clarified. This affection is characterized by a higher sensitivity to nociceptive stimulus, articular and muscular pain and associated to: fatigue, headache, sleep disorders, depression and irritated bowel syndrome. The presentation of this symptoms varied according to the patient with a heterogeneity of the clinical, physical, social and psychologic conditions and of the therapeutic responses.
Faced to the heterogeneity of FS, various hypotheses about the development mechanisms exist. Central sensitization could be one of the key mechanisms of FS, it is described as a loss of the natural balance between the transmission of a painful stimulus to the central nervous system and pain-inhibiting mechanisms, which results in permanent or chronic pain.
Moreover, work on the familial character of FS suggests that a genetic component may be involved in its development, but the identification of a genetic determinant is difficult given the multifactorial nature and complexity of FS.
The objective of this study is to characterize the predispositions of central sensitization and genetics in patients with FS compared to a control group, matched in age, sex and menopausal status.
Detailed Description
This is an exploratory case control pathophysiology study of psychophysical (central sensitization assessment) and genetic (candidate gene panel) characteristics.
The main objectives of this study are :
Primary: Evaluate the central nociception sensitization characteristics and genetic determinants in fibromyalgic syndrome, comparing a group of patients to matched healthy controls.
Secondary :
1) Characterize genetic predispositions of central sensitization in patients with FS compared to matched healthy controls, including confirmation of known genetic markers and potential identification of new genetic variants involved,
2) Compare in the area of central sensitization the population of patients with FS and matched healthy controls,
3) Compare in the domain of temporal summation the population of patients with FS and matched healthy controls,
4) Describe in the clinical field the characteristics of the FS patient population,
5) Compare in the areas of quality of life, anxiety/depression and comorbidities, characteristics of the FS patient population and matched healthy controls,
6) Compare epigenetic biomarkers of the FS patient population with healthy matched controls,
7) Study of the role of the gut microbiota in patients with FS (bio banking)
8) Compare in the areas of pain, sound and light sensitivity the population of patients with FS and matched healthy controls.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fibromyalgia
Keywords
Fibromyalgia syndrome, Chronic pain, Widespread pain, genetics, central sensitization
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
Exploratory case control pathophysiology study of psychophysical (central sensitization assessment) and genetic (candidate gene panel) characteristics.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
260 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Patient with fibromyalgia syndrome
Arm Type
Experimental
Arm Description
250 patients with fibromyalgia syndrome (according to American College of Rheumatology 2016) will realize explorations to characterize central sensitization: reflex nociceptive flexion threshold by electrophysiological measure and blood sampling for evaluate the distribution of gene polymorphism.
Arm Title
Healthy subjects
Arm Type
Sham Comparator
Arm Description
50 healthy matched volunteers (age, sex and menopausal status for women) will realize explorations to characterize central sensitization: reflex nociceptive flexion threshold by electrophysiological measure and blood sampling for evaluate distribution of gene polymorphism
Intervention Type
Device
Intervention Name(s)
Electrophysiological measurement of reflex nociceptive flexion threshold (RIII reflex) using Nicolet Vicking device
Intervention Description
This intervention measures the response to electrical stimulation of the sural nerve using a pair of percutaneous electrodes placed at the external malleolar retro passage of the nerve (2 cm apart) and connected to the stimulation device (Nicolet Vicking). Reflex muscle responses will be collected using surface electrodes placed on the femoral biceps muscle of the participant and connected to an Electromyogram recording device.
The RIII will be determined twice (rest period between each 10-minute). In order to induce the reflex nociceptive flexion response, repeated cutaneous electrical stimulations (30 to 40) will be applied at the level of the sural nerve following a variable interval of 6 to 10 seconds in order to overcome the phenomena of habituation and predictability. Each stimulus test will consist of a single rectangular pulse of 0.5 ms, of variable intensity (0-100mA) until a reflex nociceptive flexion threshold is detected or a maximum current of 100 mA is reached
Primary Outcome Measure Information:
Title
Evaluation of nociception flexion reflex (RIII) threshold by electromyography
Description
Patient rested comfortably in a supine position in order to obtain muscular relaxation. Cutaneous electrodes will be applied, and the sural nerve will be stimulated in its retromaleolar track. Electromyographic responses will recorded using the Nicolet Vicking device with a pair of surface electrodes placed over the tendon of the ipsilateral biceps femoris.
The R-III reflex (objective threshold) will be identified as a multiphasic signal appearing at least 90 ms but less than 250 ms after each stimulation and will be considered to be present when the corrected computed surface was >0.5 mV/ms (positive response).
Time Frame
Day 1
Secondary Outcome Measure Information:
Title
Evaluation of genetic polymorphism using OpenArray technology
Description
Genome-wide association studies highlight that genetic factors are possibly responsible for up to 50% of the disease susceptibility, and several potential candidate genes have been found to be associated to fibromyalgia, including catecholaminergic (COMT), serotoninergic (HTR2A, SLC6A4), dopaminergic (GCH1, TAAR1) and glutamatergic (GRIA4) pathways. The participants will be genotyped for selected SNPs (120 SNPs- OpenArray technology) that have been previously investigated in relation to FM susceptibility, symptoms or potential mechanisms (Algynomics and international publications).
A single blood sample will be obtained on visit 1 day 1 and 4 aliquotes will be frozen at -80°C and kept frozen until the Open Array Technology analysis
Time Frame
day 1
Title
Evaluation of central sensitization
Description
assessed by Central Sensitization Inventory questionnaire
Time Frame
Day 1
Title
Mechanical temporal summation by numerical scale (0 to 10)
Description
The mechanical temporal summation test will be performed using a 180g (Size 6.45) Von Frey filament applied to the non-dominant arm of the patient/subject who are sitting comfortably in a quiet room. The Von Frey filament will be applied against the skin of the participant at right angle, the manipulator performs a pressure movement until the filament flexes slightly. The participant scores on a numerical verbal scale (0 to 10) the intensity of pain perceived by the application of a single stimulus, and then of ten stimuli
Time Frame
Day 1
Title
Concise Pain Questionnaire (QCD)
Description
This self-assessment scale allows the patient to characterize the pain in relation to its psychosocial intensity and impact. The patient is asked to answer 9 graduated questions by circling a number from 0 (no pain) to 10 (the most horrible pain you can imagine). Among these questions the patient is asked to blacken the painful areas on a diagram and to put an S if the pain is on the surface or a P if it is deep
Time Frame
Day 1
Title
Detection of fibromyalgia using the FIRST questionnaire
Description
The FIRST questionnaire is a 6-item self-questionnaire that detects fibromyalgia. The patient is asked to answer "yes" or "no". Five "yes" allow to detect fibromyalgia when pain has persisted for more than 3 months
Time Frame
Day 1
Title
Evaluation of the impact of fibromyalgia using the FIQ questionnaire
Description
The revised FIQ questionnaire is a 10-item self-questionnaire that assesses the impact of fibromyalgia. The first item is subdivided into 10 questions that assess the impact of the disease in everyday life
Time Frame
Day 1
Title
Evaluation of the Suspended Symmetrical Dorsal Cellulalgia
Description
The experimenter makes a palpate-roll (by slightly lifting the skin) between the thumb and the other 4 fingers of the hand by following an axis on each side of the patient's spine. The palpate roll begins at the lumbar level and rises to the level of the shoulder blades on each side of the spine. The test is performed on one side of the spine and then on the other. The palpate roll should be performed 5 times on each side of the spine alternately. The investigator should rate for each side and at each pass whether the patient is experiencing pain or not. If the patient does not feel pain after 5 passes, the test is considered negative.
Time Frame
Day 1
Title
Quality of life by SF-36 quality of life questionnaire
Description
the quality of life of the participants will be assessed by the self-administrated General Questionnaire 36-Item Short Form Survey (SF-36). The SF-36 questionnaire consists of 36 items and assesses an individual's physical and mental health using eleven questions related to eight aspects of health: physical function, role physical, bodily pain, general health, vitality, social function, role emotional, mental health.Global score ranges from 0 to 100.
Time Frame
Day 1
Title
Emotional status by Hospital Anxiety and Depression scale (HAD)
Description
The Hospital Anxiety and Depression scale is a self-administered questionnaire in 14 items completed by the participant. It is used to determine the levels of anxiety and depression. Seven of the items relate to anxiety and seven relate to depression. Global score ranges from 0 to 42.
Time Frame
Day 1
Title
Evaluation of micro ARN using OpenArray technology
Description
Studies have shown that thousands of human protein coding genes are regulated by micro RNAs, indicating that micro RNAs are "master regulators" of many important biological processes and some of this microRNA can be implicated in fibromyalgia continuum. The participants micro RNA's will be analyzed for 754 human selected micro RNA (OpenArray technology) that have been previously investigated in relation to FM susceptibility, symptoms or potential mechanisms. A single blood sample will be obtained on visit 1 day 1 and 6 aliquotes will be frozen at -80°C and kept frozen until the Open Array Technology analysis.
Time Frame
Day 1
Title
Analysis of the microbiota (stool samples),
Description
Identification of bacterial biodiversity by a genetic sequencing analysis of bacterial DNA. The stool samples will be collected and then frozen at -80°C and kept frozen until analysis.
Time Frame
Day 1
Title
Evaluation of sensitivity to pain by PSQ questionnaire
Description
the sensitivity to pain of the participants will be assessed by the Pain Sensitivity Questionnaire (PSQ). The PSQ questionnaire explore natural sensitivity to pain using questions simulating more or less intense pain situation using 17 questions.
Time Frame
Day 1
Title
Evaluation of sensitivity to sound by audiometer
Description
the uncomfortable loudness level (ULL) of the participants will be assessed using the procedure of the British audiology society using a conventional audiometer (pure sound emission). The ULL is the level at which the participant responds or clearly feels uncomfortable and confirms this fact after removing the helmet.
Time Frame
Day 1
Title
Evaluation of sensitivity to light by led panel
Description
the light sensitivity level of the participants will be assessed using a led panel (Lykos Daylight, Manfrotto) in a room without any source of natural light. The light intensity will be progressive (by step of 1 seconds flash light every 20 seconds) and the participant will stop the test when the intensity of the light will be uncomfortable. The light sensitivity is the level at which the participant feels uncomfortable
Time Frame
Day 1
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Patient Inclusion criteria :
Patient between 18 and 65 years old (included),
Patient with fibromyalgia according to the criteria of the 2016 ACR,
Patient weighing more than 45kg
Cooperation and understanding sufficient to comply with the requirements of the study,
Acceptance to give written consent,
Affiliation to the French Social Security system,
Patient exclusion criteria :
treated with antibiotics in the three months prior to inclusion,
who has reported gastroenteritis in the two months prior to inclusion,
having a medical and / or surgical history judged by the investigator or his representative to be incompatible with the test
of childbearing age not using an effective contraceptive method, pregnant or breastfeeding woman.
participating in another clinical trial, or being in the exclusion period, or having received a total amount of benefits exceeding EUR 4500 over the 12 months preceding the start of the trial,
benefiting from a measure of legal protection (guardianship, guardianship, deprivation of liberty, safeguard of justice),
Subject inclusion criteria:
Aged of more than 18 years,
weighing more than 45kg
non-painful subjects matched by age (+/- 5 years), by sex, and by menopausal status for women,
Cooperation and understanding sufficient to comply with the requirements of the study,
Acceptance of written consent,
Affiliation to the French Social Security system,
Registration or acceptance of registration in the National Register of Volunteers participating in research.
Subject exclusion criteria :
treated with antibiotics in the three months prior to inclusion,
who has reported gastroenteritis in the two months prior to inclusion,
Medical and / or surgical history judged by the investigator or his representative to be incompatible with the test,
Intake of any drugs in the 7 days before inclusion,
Pregnant or nursing woman
Participating in another clinical trial, or within the exclusion period, or having received a total amount of compensation in excess of EUR 4500 over the 12 months preceding the start of the trial,
Benefiting from a measure of legal protection (curatorship, guardianship, safeguard of justice ...)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gisèle Pickering
Organizational Affiliation
University Hospital, Clermont-Ferrand
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHU de Clermont-Ferrand
City
Clermont-Ferrand
ZIP/Postal Code
63000
Country
France
12. IPD Sharing Statement
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FIbromyalgia anD GenetIcs Subgroups (FIDGIS)
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