Fibromyalgia and Specific Physical Activity
Phase: NA
Conditions: Fibromyalgia
Sponsor: Centre Hospitalier Departemental Vendee

 
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FibrAPSpé Protocol  
  
  
Registration No. 2018-A02881-54  
Ref : CHD 110-18  
  
  
  
"Fibromyalgia and Specific Physical Activity  
  
  
  
Coordinating Investigator :   
Thomas Rulleau, Physiotherapist,   
Clinical Research Unit,   
Bd Stéphane Moreau,   
85925 La Roche Sur Yon Cedex 9  
0251446572 ext. 22871 thomas.rulleau@chd-
vendee.fr  
  
Methodologist :   
Lucie PLANCHE  
Vendée Departmental Hospital Centre  
Clinical Research Unit lucie.planche@chd-vendee.fr   
  
  
 
  
  
  
  
Sponsor :   
   Vendée Departmental Hospital Centre  
Clinical Research Unit  
Boulevard Stéphane MOREAU  
925 LA ROCHE SUR YON Cedex  09 
85 
 
Tel : 02  
44 65  
51 
72  
Fax : 02  51 44  
85 
65  
 
 
 
 
 
 
 
 

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AMENDMENTS TO THE ORIGINAL PROTOCOL  
Version 1.1 of 10/12/2018  
  
Modification  
Pattern  
Protocol version  
Amendment 1  
Addition of an inclusion criterion  
Change in the version of the FIQ used  
2.0 of 22/05/2019  
Amendment 2  
Change of Principal Investigator at the Centre 
d'Evaluation et de Traitement de la Douleur - 
CHD Vendée - La Roche sur Yon  
2.0 of 22/05/2019  
Amendment 3  
Modification of an inclusion criterion  
Addition of the collection of analgesic and 
painkiller treatments  
Addition of 2 collaborating investigators  
3.0 of 02/10/2019  
  
  
  
  
  
  
  
 

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LIST OF ABBREVIATIONS  
  
  
ANSM  
National Agency for the Safety of Medicines and Health Products  
AMM  
Marketing Authorisation  
ARC  
Clinical Research Associate (monitor)  
GCP  
Good Clinical Practice  
CETD  
Pain Assessment and Treatment Centre   
CHD  
Departmental Hospital Centre  
CIS  
Independent Monitoring Committee  
PPC  
Committee for the Protection of Individuals   
CNIL  
Commission Nationale de l'Informatique et des Libertés  
CRF  
Case Report Form  
EAPA  
Adapted Physical Activity Teacher  
eCRF  
Electronic Case Report Form  
EMA  
European Medicines Agency  
EQ-5D-5L  
5-level EQ 5D (EQ: EuroQuol Group)  
EVA  
Visual Analogue Scale  
EvIG   
Serious Adverse Event  
ISG   
Serious Adverse Effect  
EIGI   
Unexpected Serious Adverse Effect  
FIQR  
Fibromyalgia Impact Questionnaire Revised  
HAD  
Hospital Anxiety and Depression scale  
ICH  
International Conference on Harmonization  
MR  
CNIL Reference Methodology  
CPR  
Summary of Product Characteristics  
SUSAR  
Suspected Unexpected Serious Adverse Reaction  
SSS  
Symptom Severity Scale  
TEC  
Clinical Study Technician  
WPI  
Widespread bread Index  
  
  
  
  
  
  
  
  
  

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TABLE OF CONTENTS  
  
LIST OF ABBREVIATIONS ....................................................................................................................... 3  
TABLE OF CONTENTS ............................................................................................................................... 
5 INTRODUCTION ..................................................................................  
1. 
RATIONALE FOR THE STUDY ........................................................................................................ 8  
1.1. 
POSITIONING OF THE RESEARCH ....................................................................................................... 8  
1.2. 
BENEFITS AND RISKS FOR RESEARCH SUBJECTS ............................................................................. 10  
2. 
OBJECTIVES AND JUDGING CRITERIA .................................................................................... 12  
2.1. 
OBJECTIVE AND PRIMARY ENDPOINT ............................................................................................. 12  
2.2. 
SECONDARY OBJECTIVES AND EVALUATION CRITERIA .................................................................. 12  
3. 
STUDY POPULATION ...................................................................................................................... 14  
3.1. DESCRIPTION OF THE POPULATION ....................................................................................... 14  
3.2. . INCLUSION CRITERIA ........................................................................................................... 14 
3.3. NON-INCLUSION CRITERIA ....................................................................................................... 15 
3.4. FEASIBILITY ............................................................................................................................. 15  
4. 
DESIGN AND STUDY PROCESS .................................................................................................... 16  
4.1. 
ASSESSMENT PROCEDURES.............................      ......................................................................... 16  
4.2. 
 GENERAL RESEARCH METHODOLOGY ........................................................................................... 16  
4.3. 
STUDY TECHNIQUES AND ANALYSIS ............................................................................................... 17  
4.4. 
SCHEME OF THE STUDY .................................................................................................................. 21  
4.5. 
STUDY SCHEDULE ........................................................................................................................... 22  
4.6. 
IDENTIFICATION OF ALL SOURCE DATA NOT IN THE MEDICAL RECORD ......................................... 23  
4.7. 
RULES FOR ENDING A PERSON'S PARTICIPATION ............................................................................ 23  
5. 
DATA MANAGEMENT AND STATISTICS .................................................................................. 24  
5.1. 
COLLECTION AND PROCESSING OF STUDY DATA ............................................................................ 24  
5.2. 
STATISTICS ..................................................................................................................................... 25  
6. 
VIGILANCE AND MANAGEMENT OF ADVERSE EVENTS .................................................... 28  
6.1. 
DEFINITIONS .................................       .......................................................................................... 28  
6.2. 
 LIST OF EXPECTED AES .................................................................................................................. 29  
6.3. 
MANAGING ADVERSE EVENTS ....................................................................................................... 29  
6.4. 
ARRANGEMENTS AND DURATION OF FOLLOW-UP OF INDIVIDUALS FOLLOWING THE OCCURRENCE  
OF ADVERSE EVENTS................................................................................................................................... 30  
7. 
ADMINISTRATIVE AND REGULATORY ASPECTS ................................................................. 31  
7.1. 
RIGHT OF ACCESS TO SOURCE DATA AND DOCUMENTS .................................................................. 31  
7.2. 
DATA CONFIDENTIALITY ................................................................................................................ 31  
7.3. 
COMPUTERISED DATA AND SUBMISSION TO THE CNIL .................................................................. 31 
7.4. 
MONITORING OF THE TRIAL ............................................................................................................ 31  
7.5. INSPECTION / AUDIT ....................................................................................................................... 32 
7.6. ETHICAL CONSIDERATIONS ............................................................................................................ 32 
7.7. INFORMATION TO COMPETENT AUTHORITIES ............................................................................ 32 
7.8. AMENDMENTS TO THE PROTOCOL ...................................................................................................... 33  

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7.9. FINANCING AND INSURANCE .......................................................................................................... 33 
7.10. RULES ON PUBLICATION ................................................................................................................... 33  
7.11.  ARCHIVING OF SOURCE DATA ......................................................................................................... 33  
 

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INTRODUCTION  
  
Fibromyalgia is a common, costly and controversial condition (Häuser et al., 2015; Häuser, Ablin, 
Perrot, & Fitzcharles, 2017)one of the origins of which is the sensitisation of the central nervous system 
to pain (Häuser et al., 2015).   
The usual treatment consists of multimodal management including physical activity (Häuser et al., 
2015). This dosage should be adapted to the patient's health needs (Eijsvogels & Thompson, 2015). The 
currently recommended physical exercise is aerobic work combined with muscle strengthening 
(Bidonde et al., 2017; Häuser, Ablin, Perrot, & Fitzcharles, 2017)with no evidence of superiority of 
effectiveness of one over the other (Macfarlane et al., 2017). The recommended dosage for aerobic 
exercise is 20 minutes (or twice 10 minutes), two to three times a week (70-80% of the Theoretical 
Maximum Heart Rate) (Bidonde et al., 2017; Macfarlane et al., 2017).   
At the Centre Hospitalier Départemental (CHD) Vendée, an adapted physical activity is offered to 
fibromyalgia patients thanks to the "Siel Bleu" association group. This physical activity, carried out with 
patients suffering from different pathologies, is non-specific.   
In parallel, a preliminary study has shown the benefit of lifestyle coaching with fibromyalgia patients, 
carried out by specifically trained physiotherapists, nurses and sports coaches, on quality of life 
(Hackshaw et al., 2016).   
Another possibility seems to be to offer personalised coaching with a physical activity adapted to the 
patient's physical and organisational constraints, and specific to his or her pathology. This solution 
would make it possible to adapt to the patient's choice of physical activities, to ensure better adaptation 
to their physical and organisational constraints as well as better individualised follow-up.  
 
1. RATIONALE FOR THE STUDY  
 
1.1.  
POSITIONING OF THE RESEARCH  
Fibromyalgia is a common, costly and controversial condition (Häuser et al., 2015; Häuser, 
Ablin, Perrot, & Fitzcharles, 2017). Hauser et al. report that most studies place the prevalence 
of this condition between 2 and 4% (Häuser et al., 2015). Two French studies estimate a 
prevalence of 1.4 and 1.8% (Bannwarth et al., 2017). (Bannwarth et al., 2009; Perrot, Vicaut,  
Servant, & Ravaud, 2011). The incidence would be 6.88‰ in men and 11.28‰ in women 
(Häuser et al., 2015).  

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Fibromyalgia is a complex syndrome, incorporating a wide range of symptoms and functional 
impairments (Fitzcharles et al., 2013; Häuser et al., 2015, 2017). While genetic, stress and 
environmental origins are mentioned, the inclusion of the central nervous system, with a 
"central sensitisation" to pain, seems a key element (Häuser et al., 2015). This formulation 
means that the central nervous system has a role in the modulation of pain (Williams & Gracely, 
2006) and in the development of co-morbid symptoms (sleep disorder, fatigue, memory, 
depressed mood). In addition, there are two types of subjects, those with a trigger following a 
nociceptive input and those without a triggering history (Häuser et al., 2015). It is possible that 
the triggering mechanism of central sensitisation is different (i.e.: bottom-up1 for the former 
and top-down for the latter).  
The usual treatment consists of multimodal management: functional, psychological, 
pharmacological and socio-professional. The most common non-drug treatments are: pain 
education, cognitive-behavioural treatments, multi-component therapies (education or 
psychology combined with physical exercise) and aerobic exercise (Häuser et al., 2015). The 
dosage of this physical exercise should be adapted to the patient's health needs (Eijsvogels & 
Thompson, 2015). The currently recommended physical exercise is aerobic work combined 
with muscle strengthening (Bidonde et al., 2017; Häuser et al., 2017)with no evidence of 
superiority of effectiveness of one over the other (Macfarlane et al., 2017). In addition, dry and 
aquatic exercise appear to be equally effective (Bidonde et al., 2014; Macfarlane et al.,  
2017). The recommended dosage for aerobic exercise is 20 minutes (or twice 10 minutes), two 
to three times per week (70-80% of the Theoretical Maximum Heart Rate) and 8 repetitions per 
exercise 2 to 3 times per week (Bidonde et al., 2017; Macfarlane et al., 2017). At the CHD 
Vendée, fibromyalgia patients are offered adapted physical activity with the "Siel Bleu" 
association group. This group activity is non-specific since it is carried out with patients 
suffering from different pathologies. Moreover, this activity is limited by the material 
possibilities of the association group, which cannot move heavy equipment or instruments 
(elliptical, rowing machine, swimming pool, etc.). The choice was made to offer one endurance 
session per week with a ten-minute warm-up, forty minutes of interval training and ten minutes 
of rest. Participants can log on to the association's website to follow a complementary exercise 
programme if they wish.  
                                                     
1 Bottom-up  processes use information from the sensory organs and analyse the environment on the basis of this 
information, in contrast to top-down processes which use knowledge about the structure of the environment and 
influence perception.  

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According to Bennet et al. (2009), a 14% decrease in quality of life since baseline is considered 
clinically significant (Bennett, Bushmakin, Cappelleri, Zlateva, & Sadosky, 2009). Evaluated 
in a cohort study of 10 patients (Hackshaw et al., 2016)the interest of a 37% improvement in 
quality of life following lifestyle coaching by nurses, physiotherapists and adapted physical 
activity teachers, encourages us to propose personalised coaching with a physical activity 
adapted to the patient and specific to her pathology. We believe that this solution would allow 
for adaptation to the patient's choice of physical activities, but would also allow for better 
individualised follow-up and better adaptation to the patient's physical and organisational 
constraints, with a better medium and long-term impact on quality of life.  
  
We hypothesize an improvement in the quality of life of fibromyalgia patients in the 
medium (6 months) and long term (12 months) thanks to personalized coaching (specific 
physical activity).  
The objective of our study is to compare the impact of two physical activity management in 
fibromyalgia patients at 6 and 12 months:  
1. Control group: Traditional non-specific management in a common  
"multipathology" group, with activity trackers   
2. Experimental group: Specific management in a "fibromyalgia patients" group, with 
activity trackers   
 
1.2.  
BENEFITS AND RISKS FOR RESEARCH PARTICIPANTS  
Benefits  
Individual benefit  
  
Physical activity improves pain, quality of life and body mass quality of patients.   
We expect this innovative health sport coaching to optimise these improvements (in quality of 
life, pain and body mass quality) compared to standard patient management.  
  
Collective benefit  
  
- 
This new treatment modality will improve the care available to the algologist for the 
treatment of his patients.  

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- 
We also wanted to evaluate a new, simple and rapid test of kinesiophobia using 
isochrony between an imagined movement and an executed movement to predict a patient's 
adherence to physical activity management. If this test is effective, it will allow better targeting 
of patients who can benefit from a rehabilitation programme using physical activity coaching.  
- 
Finally, an evaluation of an innovative patient monitoring with impedancemetry should 
make it possible to propose new monitoring tools for evaluating patients with fibromyalgia.  
Risks  
No excess risk due to participation in the study is expected  
In both arms of the study, the physical activity sessions are likely to cause more or less diffuse 
pain, aches, cramps, fatigue and discomfort. These symptoms are not specific to the study and 
are minimised by the supervision, which enables the absence of cardiac risk to be verified. 
Nevertheless, they may be felt as an increase in fibromyalgia pathology and experienced in a 
pejorative way by certain patients; this risk is minimised by the explanations provided within 
the framework of the research.   
The constraints associated with attending the sessions and filling in the questionnaires were 
considered minimal, but could increase the anxiety of some participants.  
 
Benefit/risk balance  
The research manager qualifies the research in the first instance as interventional research 
with minimal risks and constraints, since :  
 All procedures are performed in the usual way (assessments, clinical examinations, 
interventions in physical activities) and defined in the order of 12 April 2018 set by the 
Ministry.   
The research does not focus on innovative or obsolete techniques or strategies.  
  
Apart from the specialised physical activity offered to patients in the experimental group, the 
overall management of the patient will be identical to usual practice.   
  
Consequently, the particular modalities of implementation in the research represent negligible 
constraints for the person who lends himself to the research. (Article R 1121-3 of the Public 
Health Code (CSP), decree n° 2006-477 of 26 April 2006).  
The person in charge of the research will therefore, before any implementation of the research, 
submit the study protocol to the South-East III Committee for the Protection of Individuals 
(Comité de Protection des Personnes Sud-Est III) in accordance with Article L 1121-1 of the 

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Public Health Code (CSP) as they result from the laws n° 2004-806 of 9 August 2004 and n° 
2006-450 of 18 April 2006 relating to public health policy, for a favourable opinion and 
confirmation of the research's qualification.  
  
The bibliographical references are given in the annex to the document.  
 
2. OBJECTIVES AND JUDGING CRITERIA  
 
2.1.  
OBJECTIVE AND PRIMARY ENDPOINT  
Main objective  
To compare the benefit of a specific 6-month physical activity programme on patients' quality 
of life.  
Primary endpoint  
Evolution of the Fibromyalgia Impact Questionnaire Revised (FIQR) score (quality of life 
questionnaire specific to the management of fibromyalgia patients) between the beginning of 
the treatment (D0) and at 6 months (M6).  
 
2.2.  
OBJECTIVES AND SECONDARY EVALUATION CRITERIA  
Secondary objectives  
Compare between the 2 randomisation arms:   
  
1. 
The evolution of pain intensity between the beginning of the treatment  
(D0), at 6 months (M6) and at 12 months (M12),  
2. 
The presence of neuropathic pain and its evolution,  
3. 
The evolution of isochrony between a physically executed and mentally 
simulated movement (Moseley, 2004; Moseley et al., 2008)   
4. 
The evolution of anxiety and the presence of signs of the depressive 
series  
5. 
The evolution of pain on muscle compression  

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6. 
The severity of the symptoms   
7. 
Monitoring physical activity with activity trackers  
8. 
The evolution of lean body mass measured on an impedance scale  
9. 
The evolution of kinesiophobia  
10. 
Changes in quality of life between the start of treatment (D0) and 12 
months (M12)  
11. 
Continuity of physical activity after the end of coaching  
  
Secondary evaluation criteria  
1. 
EVA at D0, M6 and M12  
2. 
DN4 questionnaire score ≥4 at D0, M6 and M12  
3. 
Difference between the duration of the performed movement and the 
imagined movement of picking up a magazine from a table at D0, M6 
and M12  
4. 
Hospital Anxiety and Depression scale (HAD) at D0, M6 and M12  
5. 
Widespread Pain Index (WPI) (Häuser et al., 2017; Wolfe et al., 1990) 
at D0, M6 and M12  
6. 
Symptom Severity Scale (SSS) (Häuser et al., 2017; Wolfe et al., 1990) 
at D0, M6 and M12   
7. 
Percentage of success in achieving goals each month (M1-M12) as 
measured by activity tracker  
(Duration in minutes per month at least 70% of the theoretical  
maximum heart rate x100 / 240 minutes  
(4 weeks x 60 minutes recommended = 240 minutes)   
8. 
Percentage and weight of lean mass measured on an impedance scale at 
D0, M6 and M12  
9. 
Tampa self-questionnaire (Knapik, Saulicz, & Gnat, 2011) at D0, M6 
and M12  
10. 
FIQR at D0 and M12 and EQ5D-5L at D0, M6 and M12  
11. 
Level of physical activity between the groups between M6 and M12  
(the duration in minutes per month between 50 and 60, between 60 and 70, 
between 70 and 80, between 80 and 90, and between 90 and 100% of the 
theoretical maximum heart rate measured with the activity tracker)   
  
  
Exploratory secondary objective  
Evaluating the isochrony between a physically performed and mentally simulated movement as 
a predictive test of improved quality of life following a physical activity programme Isochrony 
will be assessed by the difference between the duration of the performed movement and the 
imagined movement of taking a review on a table at D0. The quality of life of the patients will 
be assessed from the FIQR score at M6 and M12.  
  

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3. STUDY POPULATION  
 
3.1.  
DESCRIPTION OF THE POPULATION  
The subjects were patients suffering from fibromyalgia, recruited during their treatment by the 
Centre d'Evaluation et de Traitement de la Douleur de Vendée (CETD) at the sites of La Roche 
sur Yon, Montaigu and Luçon, as well as at the CHU in Nantes.  
 The study plans to include 140 patients with the aim of achieving 126 randomised patients. 
Inclusion will stop when the potential number of randomised patients is reached. (see paragraph 
5 statistics).   
 
3.2.  
INCLUSION CRITERIA  
- Patient of legal age,   
- Diagnosis of fibromyalgia (Häuser et al., 2017):   
4< WPI < 6 and SSS ≥9 OR  
 WPI ≥ 6 and SSS ≥5 AND   
pain present in at least 4 of the 5 regions of the body (5 regions = 4 dials + the 
axis).  
  
- Patient with FIQR ≤ 59/100   
- Patient can be followed for 12 months in the CETD,  
- Patient able to follow the physical activities proposed by "Siel Bleu", on a physical and 
organisational level,   
- Patient with a smartphone and/or computer (mac/pc) with an internet connection allowing the 
use of a monitoring application linked to the activity tracker,  
- Patient with the ability to understand the protocol and who has given consent to participate in 
the study,  
- Patient with social security coverage.  
  
  

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3.3.  
NON-INCLUSION CRITERIA  
- Patient participating in an interventional trial within 3 months of inclusion,  
- Pregnant or breastfeeding women, or women with the potential to conceive without effective 
contraception,  
- Patient who is a minor, under guardianship, curatorship or deprived of liberty,  
- Patient unable to follow the protocol, as judged by the investigator, or unwilling to use the 
digital applications,  
- Patients with contraindications to physical activity,  
- Patients who have already taken part in the physical activities offered by "Siel Bleu".   
  
 
3.4.  
FEASIBILITY  
An investigation with the CETD-Vendée team, cross-checked with the files of the "Siel Bleu" 
association network, showed an active file of 4 new patients per week on average, i.e. 200 new 
patients per year.   
The Nantes University Hospital estimated that it would be possible to include an active file of 
24 patients per year, given their patient base and the resources required for this project.   
With a 20% refusal rate, we would have 179 patients included in the year.  
 
 
4. DESIGN AND STUDY PROCESS  
 
4.1.  
EVALUATION METHODS  
The clinical assessments will be carried out by the healthcare team (doctors and nurses) of the CETDs 
of the participating centres (La Roche Sur Yon, Luçon, Montaigu, CHU Nantes).   
These evaluators will be different from physiotherapists or adapted physical activity teachers, regardless 
of the randomisation arm.   
  

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4.2.  
GENERAL RESEARCH METHODOLOGY  
The research has the following characteristics:   
- Open study,  
- Multicentric (CHD Vendée, CHU Nantes),  
- Controlled,  
- Of superiority,  
- Randomised  
  
Duration of inclusion: 18 months  
Duration of participation: 12 months (including 6 months of adapted physical activity 
depending on the randomisation arm)    
Duration of the research: 30 months  
  
Randomisation arm :  
• 
Control group: Classic non-specific management in a common "multipathology" 
group, with activity trackers:  
- 
One face-to-face session per week with the "Siel Bleu" association in the 
different sites of the Vendée and Loire-Atlantique.  
• 
Experimental group: Specific telephone coaching for fibromyalgia patients, with 
activity trackers:  
- 
A one-hour face-to-face individual session conducted by the "Siel Bleu" 
association -  
Eight telephone coaching sessions in Physical Activity - 
Health :  
• 
Four 30-minute sessions by the "Siel Bleu" association  
• 
Four 30-minute sessions by physiotherapists from participating institutions  
The nine sessions will be spread over 6 months.   
Concerning the continuation of physical activity after the end of the experiment (i.e. after M6), the 
physical activity coaching service could be provided, if the patient so wishes and on his or her initiative, 
by a private physiotherapist or an adapted physical activity teacher from "Siel Bleu". Similarly, standard 
care is based on an existing activity currently offered by "Siel Bleu" and can therefore be integrated by 
the patient who so requests.  

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4.3.  
RESEARCH AND ANALYSIS TECHNIQUES  
Detailed description of the evaluation parameters  
The revised Fibromyalgia Impact Questionnaire (FIQR, Appendix 5) is a self-administered 
questionnaire to assess the quality of life of the fibromyalgia patient (Burckhardt, Clark, & Bennett, 
1991). Composed of 10 items, the first item includes eleven questions rated from 0 to 3 on a Likert scale. 
Items 2 and 3 ask the patient to indicate the number of days they felt well and the number of days they 
were unable to work (including housework) due to fibromyalgia symptoms. Items 4 to 10 are horizontal 
linear scales marked in 10 steps on which the patient rates work difficulties, pain, fatigue, morning 
fatigue, stiffness, anxiety and depression. The Minimum Clinically Important Difference is 14%. 
(Bennett et al., 2009). This means that a 14% difference in the FIQR score is clinically important.  
  
The Visual Analogue Scale (VAS) of pain is used to assess the progression of pain (Scott & Huskisson, 
1976). . The therapist should explain the use of the scale by presenting the ruler with the extremes: "You 
have to move the cursor, with no pain on the left and the maximum pain you can imagine on the right". 
It is marked from 0 to 100 on a ruler, the patient must move a cursor on the side without graduation. The 
therapist reports the intensity of the pain felt on the graduated side. The Minimum Detectable Change is 
11, while the Minimum Clinically Important Difference is 13.7 points out of 100. The evaluation of the 
pain will be done on the different areas of pain felt by the patient (cervical, limb).  
  
The DN4 questionnaire (Appendix 6) is used for the detection of neuropathic pain. The first part is 
based on the history, the second on a clinical examination. This questionnaire is administered by the 
therapist. If the score is greater than or equal to 4/10, the test will be considered positive (Bouhassira et 
al., 2005).  
  
The isochrony between executed and imagined movement is a test inspired by the work of Moseley 
(2004) showing an alteration in the temporality of imagined movement in chronic pain patients. Patient 
positioning: initially, the patient has the upper limb and hand at the side of the body, with the feet 30cm 
from a table. A magazine is positioned by the operator flat, at the edge and not protruding from the table.  
First, the operator will ask the patient, "On my 'go' signal, you will take the magazine lying flat in front 
of you with your dominant hand and bring the limb back along your body at your comfort speed.  
When you have brought your limb back, you will say "stop".  I will stop the clock at your end stop.  
This movement is to be done twice. The operator will note the 2 times in seconds and hundredths. In a 
second step, the operator will ask the patient: "At my starting "top", you will, without actually doing it 
and without moving, imagine taking with your dominant hand the magazine lying flat in front of you 

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and imagine bringing the limb back along your body at your comfort speed. When you have imagined 
bringing your limb back, you will say "stop". I will stop the clock at your end stop. This movement is to 
be done twice. The operator will note the 2 times in seconds and hundredths.  
  
The Hospital Anxiety and Depression scale (HAD, Appendix 8) is a screening instrument for anxiety 
and depressive disorders. It consists of 14 items rated from 0 to 3. Seven questions relate to anxiety (total 
A) and seven others to the depressive dimension (total D), thus making it possible to obtain two scores 
(maximum score for each score = 21) (Zigmond & Snaith, 1983).  
  
The Widespread Pain Index (WPI, Appendix 9) is a score given by the patient according to the 
number of affected areas (Häuser et al., 2017)  
  
The Symptom Severity Scale (SSS, Appendix 10) is scored by the patient and includes headache, pain, 
cramp in the abdomen and depression (Häuser et al., 2017)  
  
The percentage of target attainment will be calculated by averaging the attainment of monthly results, 
compared to clinical practice guidelines from the results recorded by the use of activity trackers    
 Duration in minutes per month at least 70% of the theoretical maximum heart rate x100 / 240 
minutes  
(4 weeks x 60 minutes recommended = 240 minutes)   
  
 The percentage (%) and dry mass (in kg) of lean mass will be measured on an impedance scale  
  
Analgesic and painkiller treatments: the consumption of analgesic and painkiller treatments in the week 
preceding the inclusion visits, M6 and M12 will be collected.  
  
  
The Tampa Kinesiophobia Index Scale (TSK-CF, Appendix 7) was designed and validated to estimate 
the level of kinesiophobia present in an individual at the time of assessment, with the aim of adjusting 
the intervention accordingly, and subsequently assessing whether the intervention has had an effect on 
this common problem among people with persistent pain. The higher the score, the greater the level of 
kinesiophobia. A score of 40/68 is considered significant kinesiophobia (Vlaeyen et al. 1995), and the 
Tampa scale can also be used as a follow-up criterion.  
Annex 11 consists of 2 pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ 
VAS).  
The descriptive system consists of five dimensions: mobility, personal care, usual activities, 
pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problem, mild problems, 
moderate problems, severe problems and extreme problems. The patient is asked to indicate their health 

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status by ticking the box next to the most appropriate statement in each of the 5 dimensions.   The VAS 
EQ system records the patient's self-assessed health status on a vertical visual analogue scale, where the 
assessment criteria are entitled "The best health you can imagine" and "The worst health you can 
imagine". The VAS can be used as a quantitative measure of health outcomes that reflects the patient's 
own judgement.  
The level of physical activity between the groups will be measured each month. It will be measured 
with activity trackers based on the time in minutes per month between 50 and 60, 60 and 70, 70 and 80, 
80 and 90, and 90 and 100% of the theoretical maximum heart rate.  
  
The activity trackers are OH1 wristbands from Polar™ (User Manual - Appendix 12). They retrieve, 
throughout the exercise, the heart rate of the subject thanks to optical sensors. The bracelet is either 
connected directly to a smartphone to record this frequency, or connectable to a computer in order to 
retrieve the data written in memory. There is no GPS on the bracelet. Patients will be specifically asked 
not to activate the GPS mode of the application if they are using a smartphone, in order to comply with 
the General Data Protection Regulation (GDPR) and data minimisation.   
The data is implemented on a private PolarFlow™ cloud account of the subject, accessible by personal 
private codes. The subject grants a right, retractable at any time and in real time, to transfer the data to 
PolarFlow for Coach™ (software allowing access to patient training statistics), which can be accessed 
by therapists and the person in charge of implementing the Case Report Form (CRF), again by personal 
private codes.  
 
Description of techniques and analyses  
In the control group, the adapted physical activity intervention (in a "multipathology" group) consists 
of one face-to-face session per week. The face-to-face session consists of a ten-minute warmup, followed 
by forty minutes of interval training, and then ten minutes of rest with a flash nap. The interval training 
is interspersed with two minutes of gentle, positive stimulation such as self-massage and targeted infra-
painful stretching.   
In addition, participants are offered the opportunity to log on to the association's website to do a 
complementary adapted movement activity.   
  
In the experimental group, the specific physical activity intervention consists of an individual faceto-
face coaching session carried out by an adapted physical activity teacher (EAPA). The session will 
consist of therapeutic education in order to teach the basics of physical activity, its interest in the context 
of fibromyalgia and the rules for its implementation.   

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Then, the participants will be contacted by telephone eight times over the 6 months of the intervention, 
four times by the "Siel bleu" EAPAs and four times by the physiotherapists of the participating 
establishments, in order to collect their motivations, their physical and personal constraints in carrying 
out a physical activity in line with the recommendations.   
The objective is to propose the implementation of specific physical activity(ies) according to the 
participants' constraints.  Physiotherapists and adapted physical activity teachers will have received prior 
information in order to coordinate the treatment. No paid physical activities will be offered to patients.   
Thanks to the activity trackers, the physical coaching will be based on the analysis of the participants' 
activity levels on the dedicated website.   
  
  
 
4.4.  
SCHEME OF THE STUDY  
  
 
  
  
  
  
  
 
 
Evaluation at 1 year  
Indication  
Randomisation D0  
Collection of consent and inclusion D0  
Inclusion criteria met D0  
1 st arm:   
Intervention  
AP - Specific  
nd arm 
2 
:  
Control  
AP - Standard  
Evaluation at 6 months  
Encouragement to continue  
physical activity (outside the  

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4.5.  STUDY SCHEDULE   
TIMETABLE OF THE STUDY   
  
Actions  
J0 Inclusion 
visit  
Between D0 and 
M6  
M6  
Between M6 and 
M12  
M12  
Patient information  
X  
  
  
  
  
Collection of written consent   
X  
  
  
  
  
Background  
X  
  
  
  
  
Randomisation   
X  
  
  
  
  
Clinical examination and questionnaires1  
X  
  
X  
  
X  
Encouragement to continue physical activity  
  
  
X  
  
  
Physical activity with activity trackers  
  
X  
X  
X2  
X2  
Analgesic treatments  
X  
  
X  
  
X  
Adverse events   
  
X  
X  
X  
X  
1EVA, DN4, HAD, WPI, SSS, impedance measurement, Tampa, FIQR, EQ-5D-5L         
2 Depending on the patient's choice   
 
  

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4.6.  
IDENTIFICATION OF ALL SOURCE DATA NOT IN THE MEDICAL 
RECORD  
- Physical activity: practice at inclusion and type of activity  
- Questionnaires: FIQR, DN4, Tampa, HAD, WPI, SSS, EQ-5D-5L  
- EVA  
- Physical activity during the study according to the randomisation arm (% success)  
- Impedance measurement  
 
4.7.  
RULES FOR STOPPING A PERSON'S PARTICIPATION  
Criteria for premature termination of a person's participation in research  
Any patient included in the protocol who no longer wishes to participate will be prematurely withdrawn 
from the study as soon as the request is made.  
For the modalities and duration of the follow-up of the early leavers, see the statistical section.  
  
  
-Withdrawal of patient consent at any time during the study, before publication of results.  
  
Right to object to the use of the data at any time during the study, before publication of the results  
.  
  
Procedures for premature termination of a person's participation in research    
For details of how to use the data of people who stopped the study prematurely, see the statistics section.  
  
Criteria for stopping part or all of the research (excluding biostatistical 
considerations)  
Part or all of the study may be stopped permanently or temporarily by decision of the ANSM, the CPP or 
the study sponsor.   
  
A written confirmation will be sent to the coordinating investigator of the study (specifying the reasons for 
premature termination) and to the principal investigator of each centre if applicable.  

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5. DATA MANAGEMENT AND STATISTICS  
 
5.1.  
COLLECTION AND PROCESSING OF STUDY DATA  
Data collection  
One observation book (eCRF) will be created per patient. All information required by the protocol should 
be provided in the eCRF. It should include the data needed to confirm compliance with the protocol and all 
data needed for statistical analysis; it should identify major deviations from the protocol.  
  
The persons responsible for filling in the eCRFs (investigator, CRA, etc.) must be defined and are identified 
in the table of delegation of responsibilities for each centre (kept in the investigator's folder).  
Data coding  
By signing this protocol, the principal investigator and all co-investigators agree to keep confidential the 
identities of the patients who participated in the study.   
  
The transmission of a person's data for research purposes will therefore only be possible if a coding system 
is applied; the presentation of the research results must exclude any direct or indirect identification.  
  
The identification of patients will be done according to the order of inclusion of patients by a number 
automatically assigned by the Clinsight software (eCRF) and then completed by the patients' initials.  
  
This code will be the only information that will appear on the eCRF and will allow the eCRF to be linked to 
the patient afterwards.   
The Research Manager is also required to code patient data on any documents he/she may have in his/her 
possession that are attached to the CRF.  
  
A mapping table will be set up in each centre. This table will be kept in a secure location by the centre's 
principal investigator and will contain the patient code and patient data in order to be able to trace back to 
the patient file in case of missing or erroneous data. No clinical data will be collected in these correspondence 
tables.  
Data processing  
The collection of clinical data will be based on the setting up of a database and the creation of data entry 
masks similar to the observation book in accordance with the protocol and regulations currently in force.  

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The structure of the database and input screens will be approved by the Research Manager.  
 
 
 
 
5.2.  
STATISTICS  
Description of the planned statistical methods, including the timing of planned 
interim analyses  
  
All variables will be described globally and by group. The description will include the numbers and 
percentages of modalities for qualitative variables and the minimum, maximum, mean, standard deviation 
and median for quantitative variables.  
  
Main criterion  
  
The patients' quality of life will be measured using the FIQR questionnaire at D0, M6 and M12. The 
evolution of the score at 6 and 12 months will be characterised by a graph and compared between the 2 
groups using a linear regression model taking into account the baseline score at D0, the time effect, the 
"time*group" interaction and the repeated nature of the data.   
The comparison of the evolution of the score at M6 will be tested from the M6 contrast.  
  
  
Secondary criteria   
  
The evolution of pain will be graphically characterised and compared using a mixed linear regression model 
taking into account the baseline data of the D0 score and the repeated nature of the data.  
  
Neuropathic pain will be assessed using the DN4 questionnaire score. It will be compared between the two 
groups using a mixed generalized linear regression model taking into account the repeated nature of the data.  
  
The evolution of the isochrony will be characterised graphically and compared using a mixed linear 
regression model taking into account the baseline data J0 and the repeated nature of the data.  
  
The evolution of anxiety will be assessed from the total HAD score and compared between the two groups 
using a mixed linear regression model taking into account the baseline D0 score and the repeated nature of 
the data.  
  
The evolution of pain on muscle compression will be assessed from the total WPI score and compared 
between the two groups using a mixed linear regression model taking into account the baseline score on D0 
and the repeated nature of the data.  
  
  

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The severity of symptoms will be measured from the SSS score and compared using a mixed linear 
regression model taking into account the baseline data of the D0 score and the repeated nature of the data.  
  
Physical activity monitoring will be collected every month until M12. Each month, the percentage of goal 
achievement will be calculated. The average percentage of success will be plotted and compared between 
the 2 groups using a mixed linear regression model taking into account the repeated nature of the data.  
  
The evolution of lean body mass will be collected at D0 M6 and M12 and compared using a mixed linear 
regression model taking into account the repeated nature of the data.  
  
  
The evolution of kinesiophobia will be assessed using the TAMPA self questionnaire at D0, M6 and M12. 
The total score will be compared between the groups using a mixed linear regression model taking into 
account the baseline score on D0 and the repeated nature of the data.  
  
  
The evolution of the quality of life will be measured using the EQ5D-5L questionnaire at D0, M6 and M12. 
The evolution of the score will be characterised by a graph and compared between the 2 groups using a 
mixed linear regression model taking into account the baseline score on D0 and the repeated nature of the 
data.  
  
Exploratory criterion   
The evolution of the FIQR score will be evaluated using a linear mixed model taking into account the group 
and repeated nature of the data as well as the isochrony data at D0 in order to evaluate its predictive character.  
Statistical justification of the number of inclusions  
The study is a superiority trial on the decrease of the FIQR score (improvement of the quality of life) at 6 
months between a control group (classic non-specific management in a common "multipathology" group) 
and an experimental group (specific management in a "fibromyalgia patients" group).  
According to Hackshaw et al. (2016), the mean baseline QoL of the ten patients included was 49.4 (13.8) on 
the FIQR scale. After 6 months of intervention (life coaching including physical activity), the mean level of 
quality of life was 31.0 (13.2), i.e. a decrease in score of 18.4 points (37% decrease).  
Evidence of a 7-point difference between the two intervention groups at M6 will be considered clinically 
significant.  
With a power of 80%, and an alpha risk of 5%, 114 patients will be needed to show this difference. To ensure 
the necessary power, an additional 10% of patients will be included, for a total of 126 patients.  
Expected level of statistical significance  
The alpha risk is set at 5%.  

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Statistical criteria for stopping the research  
NA  
  
Method of accounting for missing, unused or invalid data  
All missing data and the reason for it will be described in each group.  
  
The FIQR score will be estimated and compared between the 2 groups using a linear model taking into 
account the repeated nature of the data, so no imputation method will be applied.  
Managing changes to the original strategy analysis plan  
NA  
Selection of persons to be included in the analyses  
The main analysis will be performed on the Intent-to-Treat (ITT) population, i.e. on all randomised patients.  
A sensitivity analysis will be performed on the Per Protocol (PP) population including randomised patients 
for whom no major protocol deviations were identified.  
A data review meeting will be held to review and define the major criterion or not for each of the deviations.  
Randomisation  
Randomisation will be carried out in a 1:1 ratio and will be done in blocks.  
  
Randomisation will be carried out in Ennov Clinical by connecting to the website: https://www.dirc-
hugo-online.org/csonline/. The connection will be made through a login, a password and a study 
number, delivered by the data manager of the Research Unit of the La Roche sur Yon Hospital. The 
following information must be filled in:  
  
-First initial of the name,  
  
-First initial of the first name,  
  
-Month and Year of birth,  
  
Compliance with inclusion and non-inclusion criteria (yes/no),  
  
  
Randomisation will be carried out by the investigator after confirmation of the possibility of 
inclusion in the study. The inclusion number will be assigned automatically during randomisation. 

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An email confirmation will be sent to the person who performed the randomisation and to all 
persons involved.  
  
The randomisation list will be carried out by the statistician of the Research Unit of the CHD of La 
Roche sur Yon. An explanatory guide to randomisation will be available online in Ennov Clinical   
 
  
6. VIGILANCE AND MANAGEMENT OF ADVERSE 
EVENTS  
6.1.  
DEFINITIONS  
    
Vigilance  
It is the monitoring of medicines, medical devices and other health 
products. It also consists of the prevention of the risk of adverse effects 
resulting from their use, whether this risk is potential or proven,  
Adverse events (AEs)  
Any harmful event occurring in a person who is a subject of research 
involving the human person, whether or not the event is related to the 
research or the product to which the research relates.  
Intensity of Adverse Events 
(AEs)  
It will be scored according to the criteria chosen when the protocol was 
drafted   
For any event not noted in the chosen classification, the rating will be 
as follows: 1 = benign  
2 = moderate  
3 = severe  
4 = life-threatening  
5 = death  
Adverse effects (AEs)  
An adverse event occurring in a person who is a subject of research 
involving the human subject, where that event is related to the research 
or the product to which the research relates.  
Serious 
adverse 
events 
(SAEs)/Events (SAEs)  
Any adverse effect/event that :  
* 
results in death,  
* 
is life-threatening,  
* 
results in temporary or permanent incapacity or disability,  
* 
requires or prolongs the patient's hospitalization,  
* 
causes a congenital or neonatal anomaly,  
* 
is medically important (the list of medically important 
effects/events is defined by the EMA).  

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Unexpected adverse events 
(AEs)  
Any adverse reaction whose nature, severity or course is not consistent 
with the information about the products, procedures and methods used 
in the research.  
New fact  
Any new information that may lead to a reassessment of the riskbenefit 
balance of the research or the investigational product, to changes in the 
use of the investigational product, in the conduct of the research, or in 
the documentation of the research, or to the suspension or 
discontinuation or modification of the research protocol or similar 
research. For trials involving the first administration or use of a health 
product in persons without medical conditions: any serious adverse 
reaction.  
Abuse  
Intentional, persistent or sporadic excessive use of a drug that is 
accompanied by harmful physical or psychological reactions.  
Overdose  
Administration of an amount of drug, given at one time or 
cumulatively, that is above the maximum recommended dose according 
to the rules of compliance or use of the product. Clinical judgement 
should always be applied.   
 
(actual overdose: due to too much raw material / relative overdose: due to 
predisposing 
factors of the patient 
such as renal insufficiency, 
hypoalbuminemia...)  
Misuse or off-label use  
Situation where the product is intentionally used in a way that does not 
comply with the specifications for use of the product (e.g. different 
route of administration/posology or indication than listed in the 
reference document).  
Medication error (ME)  
Corresponds to any omission or unintentional, proven (or potential) 
performance of an act during the care process, in the circuit (from 
manufacture to administration) involving a product that may be the 
cause of a risk or an adverse event for the patient. The risk of error or 
potential error concerns situations where the error has not occurred, has 
been intercepted but could have occurred  
 
6.2.  
LIST OF EXPECTED ARS  
Within the framework of this protocol, the expected ARs are :   
  
Concerning physical activity :   
ARs related to physical activity are of the following types:  
- 
musculoskeletal problems with more or less diffuse pain (limbs, neck, back, abdomen...), aches, 
contractures, cramps, musculoskeletal trauma including tendonitis...    
- 
general/metabolic: hunger, malaise, shortness of breath, weight loss, weight gain.  
  
Regarding the usual drug treatments for the disease:   
The prescription of treatments is not modified by participation in the study. Given their diversity, it is not 
possible to propose an exhaustive list of expected effects.  

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The medicinal management of fibromyalgia and associated symptoms involves various pharmacological 
classes. The drugs are used within the framework of their MA and the expected AEs are listed in the current 
SPCs of the specialities concerned.  
  
Medical devices can also be used (TENS, etc.) within the framework of their indications, their AEs are 
mentioned in the instructions for use.   
 
6.3.  
MANAGING ADVERSE EVENTS  
Collection of EvI/EI  
In this minimal risk, minimal burden research, the protocol does not involve any changes to the usual 
management of patients.  
  
The AEs related to the pathology studied (fibromyalgia), its treatment, the co-pathologies and their 
respective treatments, are neither to be entered in the vigilance part of the CRF, nor to be notified.   
  
Under the responsibility of the investigator, as in the case of care, the notification of complications and AEs 
is part of the regulated systems: AEs related to drugs and DMs transmitted to the pharmacovigilance systems, 
materialovigilance, complications of procedures and examinations integrated into the risk management 
system of the institutions, etc...    
The data concerning fibromyalgia and its evolution are traced in the dedicated part of the CRF.   
  
In the framework of this study, which aims at the interest of a specific 6-month physical activity programme 
on the quality of life of the patients, only the complications and AEs of the techniques having a potential 
impact on the protocol objective will be collected and notified if a severity criterion exists:  
- functional problems following the sessions that prevent the performance/continuation of physical activity  
-malfunction of the activity tracking system  
  
All developments and pregnancies that occur during the study will be traced and reported to the sponsor.     
Notification of SAEs / EvIG  
EvIGs and EIGs are notified to the appropriate vigilance circuits (a copy will be kept in the patient's clinical 
file).  
  
In the context of this protocol, new developments, special situations, and complications that may impact the 
study objective are listed in the CRF and will be taken into account in the analyses planned according to the 
study schedule.   
  

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Only new developments and malfunctions in the tracking system should be reported to the promoter without 
delay after becoming aware of them so that corrective measures can be put in place.   
  
Notification period to the promoter  
The investigator is responsible for collecting and reporting to the appropriate monitoring system the various 
complications presented by patients.  
It is the investigator's responsibility to record and report all AEs/SGEs, special situations or developments, 
as described above, whether expected or not, occurring during the entire study:  
-  from the date of signature of the randomisation - 
 
and until the end of the study (i.e. M12)  
6.4. MODALITIES AND DURATION OF FOLLOW-UP OF INDIVIDUALS 
FOLLOWING THE OCCURRENCE OF ADVERSE EVENTS  
Any event, especially a serious one, must be followed up until recovery, consolidation or death (closed 
event).   
Every pregnancy should be monitored at least until the birth of the child.  
 
7. ADMINISTRATIVE AND REGULATORY ASPECTS  
 
7.1.  
RIGHT OF ACCESS TO SOURCE DATA AND DOCUMENTS  
The medical data of each patient will be transmitted only to the sponsor or any person duly authorised by 
the sponsor, and, where appropriate, to the authorised health authorities, under conditions that guarantee 
their confidentiality.   
The sponsor and the regulatory authorities may request direct access to the medical record for verification 
of the clinical trial procedures and/or data, and within the limits permitted by the laws and regulations.  
  
 
7.2.  
DATA PRIVACY  
Persons with direct access shall take all necessary precautions to ensure the confidentiality of information 
relating to the persons who have access, in particular as regards their identity and the results obtained. These 

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persons, as well as the investigators themselves, are subject to professional secrecy (according to the 
conditions defined by articles 226-13 and 226-14 of the penal code).  
During or after the research, the data collected on the subjects and transmitted by the participants will be 
made anonymous.  
Under no circumstances should the names of the persons concerned or their addresses appear in clear text.  
Only the first two letters of the subject's name and the first letter of the subject's first name will be recorded, 
along with a study-specific code number indicating the order of inclusion of subjects.   
  
 
7.3.  
COMPUTERISED DATA AND SUBMISSION TO THE CNIL  
This study falls within the scope of the "Reference Methodology" (MR-001) in application of the provisions 
of Article 54 paragraph 5 of Law No. 78-17 of 6 January 1978, as amended, relating to information 
technology, files and freedoms. This change was approved by decision of 14 August 2016.  The CHD Vendée 
in La Roche sur Yon, the study's promoter, signed a commitment to comply with this "Reference 
Methodology".   
In view of the risk to the rights and freedoms of research participants (use of a new technology), an impact 
assessment will be carried out.   
 
7.4.  
MONITORING OF THE TRIAL  
Monitoring will be carried out by the Promotion Department of the Research Directorate. A Clinical 
Research Associate (CRA) will regularly visit each site (investigator and pharmacy) in order to carry out 
quality control of the data reported in the observation books.  
  
The protocol has been classified according to the estimated level of risk to the patient undergoing the 
research. It will be monitored as follows:   
Risk A: low or negligible foreseeable risk  
  
On-site monitoring visits will be organised after an appointment with the investigator. During these visits, 
the following will be reviewed  
- 
informed consent  
- 
compliance with the study protocol and the procedures defined therein  
- 
quality of the data collected in the observation book: accuracy, missing data, consistency of data 
with "source" documents (medical records, appointment books, original laboratory results, etc.) - 
management of any products.  

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7.5.  
INSPECTION / AUDIT  
In the context of this study, an inspection or audit may take place. The sponsor and/or the participating 
centres must be able to give access to the data to the inspectors or auditors.  
 
 
7.6.  
ETHICAL CONSIDERATIONS  
Patient information  
Patients will be fully and fairly informed, in understandable terms, of the objectives and constraints of the 
study, of their rights to refuse to participate in the study or of the possibility to withdraw at any time.  
  
All of this information is contained in an information and consent form given to the patient. The patient's 
free, informed and written consent will be obtained by the investigator, or a physician representing the 
investigator, before final inclusion in the study. A copy of the information and consent form signed by both 
parties will be given to the patient, and the investigator will retain the original.  A copy will be placed at the 
end of the study in a sealed tamper-proof envelope containing all the consent forms, which will be archived 
by the sponsor.  
Committee for the Protection of Individuals  
The sponsor undertakes to submit the study project for prior authorisation by a Personal Protection 
Committee (CPP). The information communicated concerns, on the one hand, the modalities and nature of 
the research and, on the other hand, the guarantees provided for the patients participating in this trial.  
  
 
7.7.  
INFORMATION TO THE COMPETENT AUTHORITIES  
This protocol will be reported to the ANSM.  
  
 
7.8.  
AMENDMENTS TO THE PROTOCOL  
Requests for substantial changes will be sent by the promoter to the relevant CPP for its opinion in 
accordance with the law in force and its implementing decrees.  
  

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An updated dated version of the amended protocol will be required.  
The information and consent form will need to be amended if necessary.  
 
7.9.  
FINANCING AND INSURANCE  
The promoter finances the study and takes out an insurance policy to cover the financial consequences of its 
civil liability, in accordance with the regulations.  
 
7.10.  RULES ON PUBLICATION  
Authorship will be in accordance with the International Committee of Medical Journal Editors' rules for 
publication of research papers submitted to medical journals. The project leader, Thomas Rulleau, will be 
listed as first author. Yves-Marie Pluchon, or in the case of a change of institution, his replacement at the 
CETD of the CHD, will appear as the last author. The other authors will appear in the following order: 
François Etcheverrigaray, second author, Lucie Planche, third author, Margot Miot, fourth author, Aline 
Liaigre, fifth author, and the principal investigator of the secondary centre, penultimate author.  
  
 
7.11.  ARCHIVING OF SOURCE DATA  
The investigator must keep all information about the study for at least 15 years after the end of the study. At 
the end of the study, the investigator will also receive a copy of the data of each patient in his centre via a 
CD-ROM sent by the institution responsible for the Research.  
 
 
 

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