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Montpellier PROspective Cohort in Relapsing Remitting Multiple Sclerosis Using Imaging and Serologic (PROMISE)

Primary Purpose

Multiple Sclerosis

Status
Not yet recruiting
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Magnetic Resonance Imaging
Blood withdrawal
Neuropsychological tests
Sponsored by
University Hospital, Montpellier
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Multiple Sclerosis focused on measuring Multiple sclerosis, MRI, Longitudinal cohort, Real life, Biomarkers

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patients over 18 and under 55 years of age Patients with Relapsing-remitting MS without relapse for at least 6 months EDSS<6 at time of inclusion Exclusion Criteria: Secondary progressive MS or Primary progressive MS at time of inclusion Evidence of disease progression (clinical or radiological) Change in treatment in the year prior to inclusion Subject with a contraindication to MRI (claustrophobia, pacemaker, etc.) Inability to follow the follow-up planned by the study Pregnant or breastfeeding women Patient not affiliated to the social security system or not benefiting from such a system Adult protected by law or patient under guardianship or curatorship Failure to obtain written informed consent after a reflection period

Sites / Locations

  • Neurology Department, Hopital Gui de Chauliac

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Relapsing-remitting Multiple sclerosis benefiting from a moderately effective treatment

Relapsing-remitting Multiple sclerosis benefiting from a highly effective treatment

Untreated relapsing-remitting Multiple sclerosis

Arm Description

Moderately effective treatment includes interferon beta, glatiramer acetate, Teriflunomide, dimethyl Fumarate and monomethyl fumarate n= 175 patients

Highly effective treatment includes Natalizumab, Ocrelizumab, Rituximab, Ofatumumab, Fingolimod and Cladribine n= 175 patients

Patients untreated for relapsing-remitting Multiple sclerosis n= 50 patients

Outcomes

Primary Outcome Measures

Total brain atrophy
Total brain atrophy measured with T1 MRI scans

Secondary Outcome Measures

Quantitative analysis: analysis of FLAIR hypersignals number
Analysis of FLAIR hypersignals numbers (lesion load)
Quantitative analysis: analysis of FLAIR hypersignals volume
Analysis of FLAIR hypersignals volume
Qualitative analysis: analysis of central vein lesions
Identification and quantification of central vein lesions on SWI
Qualitative analysis: analysis of peripheral rim lesion
Identification and quantification of peripheral rim lesions on SWI
Quantitative analysis: measurement of mean diffusivity
measurement of the mean diffusivity using diffusion tensor analysis
Quantitative analysis: measurement of anisotropy fraction
measurement of anisotropy fraction using diffusion tensor analysis
Quantitative analysis: measurement of cerebral blood flow (CBF)
cerebral blood flow analysis on 3DPCASL
Changes in serum light chain neurofilament values
Changes in serum light chain neurofilament values in patients with RRMS patients according to the treatment line (high efficacy treatment vs. medium efficacy treatment)
Clinical assessment scale: relapses
Clinical assessment scales (absolute changes and reaching threshold values): Relapses
Clinical assessment scale: Expanded Disability Status Scale (EDSS)
The EDSS scale ranges from 0 to 10 in 0.5 unit increments that represent higher levels of disability. Scoring is based on an examination by a neurologist.
Clinical assessment scale: Computerized Speed Cognitive Test (CSCT)
" Computerized Speed Cognitive Test " (CSCT) provides screening for cognitive impairment in MS patients
Clinical assessment scale: Six-Minute Walk Test (6MWT)
Six-Minute Walk Test
Clinical assessment scale: 9-Hole Peg Test (9-HPT)
The 9-HPT is a brief, standardized, quantitative test of upper extremity function.
Clinical assessment scale: Timed 25-Foot Walk (T25-FW)
The T25-FW is a quantitative mobility and leg function performance test based on a timed 25-walk.
Quality of life scale: The 5-level EQ-5D questionnaire (EQ5D-5L)
EQ5D5L comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. Lower score indicate better outcomes. The questionnaire also includes a visual analog scale in which the patient quantifies his or her perception of quality of life using a score ranging from the worst imaginable state of health (0) to the best imaginable state of health (100).
Quality of life scale: The Brief Pain Inventory (BPI)
The Brief Pain Inventory (BPI) assesses the severity of pain and its impact on functioning.
Quality of life scale: DN4
The "Douleur Neuropathique 4 questions" questionnaire is a 4 questions questionnaire on neuropathic pain rating from 0 to 10; If the patient's score is 4/10 or more, the test is positive When the practitioner suspects neuropathic pain, the DN4 questionnaire is useful as a diagnostic tool.
Fatigue scale: Chalder Fatigue Scale
Chalder Fatigue Scale is a self-administered questionnaire for measuring the extent and severity of fatigue.
Fatigue scale: Modified Fatigue Impact Scale (MFIS)
Modified Fatigue Impact Scale (MFIS) provides an assessment of the effects of fatigue in terms of physical, cognitive, and psychosocial functioning.
Sleep scale: Epworth Sleepiness Scale (ESS)
The Epworth Sleepiness Scale (ESS) is used to assess daytime sleepiness.The ESS is a self-administered questionnaire with 8 questions. ESS score can range from 0 to 24. A global score greater than ten is diagnostic of excessive daytime sleepiness .
Depression scale: Beck Depression Inventory (BID)
The Beck Depression Inventory (BDI) contains 21 items and identifies symptoms and attitudes associated with depression.
Anxiety scale: Generalized Anxiety Disorder 7-Item Scale (GAD-7)
Generalized Anxiety Disorder 7-Item Scale measures seven anxiety symptoms.
Headaches scale: ef-ID Migraine
ef-ID Migraine guide towards the diagnosis of migraine
Exploratory criteria:Serum Glial Fibrillary Acidic Protein (GFAP)
Serum GFAP
Exploratory criteria: Pittsburgh Sleep Quality Index (PSQI) questionnaire
Evaluation of habitual sleep quality trough a validated questionnaire. 19 items where each item is weighted on a 0-3 interval scale. The global PSQI score is then calculated by totaling the seven component scores, providing an overall score ranging from 0 to 21, where lower scores denote a healthier sleep quality.
Exploratory criteria: Idiopathic Hypersomnia Severity Hypersomnia Scale (IHSS)
Patient-reported questionnaire assessing the severity of excessive sleepiness, prolonged sleep duration, cognitive impairment and sleep inertia. The total score ranges from 0 to 50, with higher scores indicating more severe symptoms.
Exploratory criteria: RU SATED score
The Regularity, Sleep Quality, Alertness, Timing, Efficiency, Duration scale for sleep (RU SATED) ranges from 0 to 30, with higher scores indicating better sleep health.
Exploratory criteria: Insomnia Severity Index (ISI)
The Insomnia Severity Index is a seven item-scale scored on a five-point scale (from 0 to 4). The total score ranges from 0 to 28. Higher scores indicate more insomnia.
Exploratory criteria: Headaches Impact Test (HIT-6)
HIT-6 addresses six main domains affected by headaches, including pain, social functioning, role functioning, cognitive functioning, vitality and psychological stress. Little or no impact: 49 or less ; some impact: 50-55 ; substantial impact: 56-59 ; severe impact: 60-78
Exploratory criteria: Godin Leisure-Time Exercise Questionnaire (GLTEQ)
Godin Leisure-Time Exercise Questionnaire (GLTEQ)

Full Information

First Posted
June 15, 2023
Last Updated
July 18, 2023
Sponsor
University Hospital, Montpellier
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1. Study Identification

Unique Protocol Identification Number
NCT05962177
Brief Title
Montpellier PROspective Cohort in Relapsing Remitting Multiple Sclerosis Using Imaging and Serologic
Acronym
PROMISE
Official Title
Montpellier PROspective Cohort in Relapsing Remitting Multiple Sclerosis Using Imaging and Serologic
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
July 2023 (Anticipated)
Primary Completion Date
July 2028 (Anticipated)
Study Completion Date
July 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Montpellier

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
Several prospective monocentric cohorts of between 250 and 1000 patients have been set up in order to characterize more precisely the evolution of the disease. Nevertheless, due to an initial recruitment carried out in the years 2000-2010, they do not constitute a faithful representation of the patients followed in clinical routine, in particular in terms of distribution of treatments. Indeed, the introduction, about 10 years ago, of high efficacy treatments (HET) has changed the management of the disease and a significant proportion of patients not controlled by medium efficacy treatments (MET) of the disease are now stable on HET. Nevertheless, if their short-term efficacy has been clearly demonstrated, it remains important to be able to confirm the superiority of HET over MET with the help of prospective cohorts (thus ensuring a retention of patients > 90% over the long term) analyzing all clinical and imaging biomarkers, imaging and biological data. The measurement of cerebral atrophy and its progression is probably one of the most interesting and most easily used biomarkers that can be used clinically to assess this silent progression in these groups of patients. The progression of brain atrophy is also dependent on many other non-modifiable but also modifiable factors outside of MS that need to be better evaluated and eventually managed. Nevertheless, the existence of various neurological comorbidities (sleep disorders, headaches) on this atrophy has not been specifically analyzed to date. The functional assessments used in routine follow-up are most often performed in a care facility and have many limitations: lack of reproducibility, inter/intra operator variability, poor correlation with functional and quality of life scales, etc. It is therefore extremely important to be able to identify new clinical biomarkers of disease progression of the disease by evaluating the physical capacities of the patients as precisely as possible. This study is a single-center, prospective cohort study of a population of 400 patients with relapsing remitting MS (RRMS). The main objective of this study is to compare, on morphological imaging criteria (T1 volumetry), the progression of brain atrophy (biomarker of disease progression) at 3 years in RRMS patients according to treatment line (MET vs HET).
Detailed Description
Several prospective monocentric cohorts of between 250 and 1000 patients have been set up in order to characterize more precisely the evolution of the disease. Nevertheless, due to an initial recruitment carried out in the years 2000-2010, they do not constitute a faithful representation of the patients followed in clinical routine, in particular in terms of distribution of treatments. Indeed, the introduction, about 10 years ago, of high efficacy treatments (HET : Natalizumab, Fingolimod, Ocrelizumab, Rituximab, Ofatumumab, Cladribine) has changed the management of the disease and a significant proportion of patients not controlled by medium efficacy treatments (MET : Beta interferons, glatiramer acetate, teriflunomide, dimethyl fumarate, monomethyl fumarate) of the disease are now stable on HET. Nevertheless, if their short-term efficacy has been clearly demonstrated, it remains important to be able to confirm the superiority of HET over MET with the help of prospective cohorts (thus ensuring a retention of patients > 90% over the long term) analyzing all clinical and imaging biomarkers, imaging and biological data. The measurement of cerebral atrophy and its progression is probably one of the most interesting and most easily used biomarkers that can be used clinically to assess this silent progression in these groups of patients. The progression of brain atrophy is also dependent on many other non-modifiable but also modifiable factors outside of MS that need to be better evaluated and eventually managed. Nevertheless, the existence of various neurological comorbidities (sleep disorders, headaches) on this atrophy has not been specifically analyzed to date. The functional assessments used in routine follow-up are most often performed in a care facility and have many limitations: lack of reproducibility, inter/intra operator variability, poor correlation with functional and quality of life scales, etc. It is therefore extremely important to be able to identify new clinical biomarkers of disease progression of the disease by evaluating the physical capacities of the patients as precisely as possible. This study is a single-center, prospective cohort study of a population of 400 patients with relapsing remitting MS (RRMS). The main objective of this study is to compare, on morphological imaging criteria (T1 volumetry), the progression of brain atrophy (biomarker of disease progression) at 3 years in RRMS patients according to treatment line (MET vs HET). 3 groups of interest will be studied and included in the study: Group 1: RRMS with medium efficacy treatment (interferon beta, glatiramer acetate, Teriflunomide, dimethyl fumarate, monomethyl fumarate) of the disease (n=175 patients) Group 2: RRMS with high efficacy treatment (Natalizumab, Ocrelizumab, Rituximab, Ofatumumab, Fingolimod, Cladribine: n=175 patients) Group 3: Untreated RRMS (n=50 patients)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis
Keywords
Multiple sclerosis, MRI, Longitudinal cohort, Real life, Biomarkers

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
400 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Relapsing-remitting Multiple sclerosis benefiting from a moderately effective treatment
Arm Type
Experimental
Arm Description
Moderately effective treatment includes interferon beta, glatiramer acetate, Teriflunomide, dimethyl Fumarate and monomethyl fumarate n= 175 patients
Arm Title
Relapsing-remitting Multiple sclerosis benefiting from a highly effective treatment
Arm Type
Experimental
Arm Description
Highly effective treatment includes Natalizumab, Ocrelizumab, Rituximab, Ofatumumab, Fingolimod and Cladribine n= 175 patients
Arm Title
Untreated relapsing-remitting Multiple sclerosis
Arm Type
Experimental
Arm Description
Patients untreated for relapsing-remitting Multiple sclerosis n= 50 patients
Intervention Type
Other
Intervention Name(s)
Magnetic Resonance Imaging
Intervention Description
Magnetic Resonance Imaging
Intervention Type
Other
Intervention Name(s)
Blood withdrawal
Intervention Description
Blood withdrawal
Intervention Type
Other
Intervention Name(s)
Neuropsychological tests
Intervention Description
Neuropsychological tests
Primary Outcome Measure Information:
Title
Total brain atrophy
Description
Total brain atrophy measured with T1 MRI scans
Time Frame
3 years after Day 1
Secondary Outcome Measure Information:
Title
Quantitative analysis: analysis of FLAIR hypersignals number
Description
Analysis of FLAIR hypersignals numbers (lesion load)
Time Frame
3 years after Day 1
Title
Quantitative analysis: analysis of FLAIR hypersignals volume
Description
Analysis of FLAIR hypersignals volume
Time Frame
3 years after Day 1
Title
Qualitative analysis: analysis of central vein lesions
Description
Identification and quantification of central vein lesions on SWI
Time Frame
3 years after Day 1
Title
Qualitative analysis: analysis of peripheral rim lesion
Description
Identification and quantification of peripheral rim lesions on SWI
Time Frame
3 years after Day 1
Title
Quantitative analysis: measurement of mean diffusivity
Description
measurement of the mean diffusivity using diffusion tensor analysis
Time Frame
3 years after Day 1
Title
Quantitative analysis: measurement of anisotropy fraction
Description
measurement of anisotropy fraction using diffusion tensor analysis
Time Frame
3 years after Day 1
Title
Quantitative analysis: measurement of cerebral blood flow (CBF)
Description
cerebral blood flow analysis on 3DPCASL
Time Frame
3 years after Day 1
Title
Changes in serum light chain neurofilament values
Description
Changes in serum light chain neurofilament values in patients with RRMS patients according to the treatment line (high efficacy treatment vs. medium efficacy treatment)
Time Frame
3 years after Day 1
Title
Clinical assessment scale: relapses
Description
Clinical assessment scales (absolute changes and reaching threshold values): Relapses
Time Frame
3 years after Day 1
Title
Clinical assessment scale: Expanded Disability Status Scale (EDSS)
Description
The EDSS scale ranges from 0 to 10 in 0.5 unit increments that represent higher levels of disability. Scoring is based on an examination by a neurologist.
Time Frame
3 years after Day 1
Title
Clinical assessment scale: Computerized Speed Cognitive Test (CSCT)
Description
" Computerized Speed Cognitive Test " (CSCT) provides screening for cognitive impairment in MS patients
Time Frame
3 years after Day 1
Title
Clinical assessment scale: Six-Minute Walk Test (6MWT)
Description
Six-Minute Walk Test
Time Frame
3 years after Day 1
Title
Clinical assessment scale: 9-Hole Peg Test (9-HPT)
Description
The 9-HPT is a brief, standardized, quantitative test of upper extremity function.
Time Frame
3 years after Day 1
Title
Clinical assessment scale: Timed 25-Foot Walk (T25-FW)
Description
The T25-FW is a quantitative mobility and leg function performance test based on a timed 25-walk.
Time Frame
3 years after Day 1
Title
Quality of life scale: The 5-level EQ-5D questionnaire (EQ5D-5L)
Description
EQ5D5L comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. Lower score indicate better outcomes. The questionnaire also includes a visual analog scale in which the patient quantifies his or her perception of quality of life using a score ranging from the worst imaginable state of health (0) to the best imaginable state of health (100).
Time Frame
3 years after Day 1
Title
Quality of life scale: The Brief Pain Inventory (BPI)
Description
The Brief Pain Inventory (BPI) assesses the severity of pain and its impact on functioning.
Time Frame
3 years after Day 1
Title
Quality of life scale: DN4
Description
The "Douleur Neuropathique 4 questions" questionnaire is a 4 questions questionnaire on neuropathic pain rating from 0 to 10; If the patient's score is 4/10 or more, the test is positive When the practitioner suspects neuropathic pain, the DN4 questionnaire is useful as a diagnostic tool.
Time Frame
3 years after Day 1
Title
Fatigue scale: Chalder Fatigue Scale
Description
Chalder Fatigue Scale is a self-administered questionnaire for measuring the extent and severity of fatigue.
Time Frame
3 years after Day 1
Title
Fatigue scale: Modified Fatigue Impact Scale (MFIS)
Description
Modified Fatigue Impact Scale (MFIS) provides an assessment of the effects of fatigue in terms of physical, cognitive, and psychosocial functioning.
Time Frame
3 years after Day 1
Title
Sleep scale: Epworth Sleepiness Scale (ESS)
Description
The Epworth Sleepiness Scale (ESS) is used to assess daytime sleepiness.The ESS is a self-administered questionnaire with 8 questions. ESS score can range from 0 to 24. A global score greater than ten is diagnostic of excessive daytime sleepiness .
Time Frame
3 years after Day 1
Title
Depression scale: Beck Depression Inventory (BID)
Description
The Beck Depression Inventory (BDI) contains 21 items and identifies symptoms and attitudes associated with depression.
Time Frame
3 years after Day 1
Title
Anxiety scale: Generalized Anxiety Disorder 7-Item Scale (GAD-7)
Description
Generalized Anxiety Disorder 7-Item Scale measures seven anxiety symptoms.
Time Frame
3 years after Day 1
Title
Headaches scale: ef-ID Migraine
Description
ef-ID Migraine guide towards the diagnosis of migraine
Time Frame
3 years after Day 1
Title
Exploratory criteria:Serum Glial Fibrillary Acidic Protein (GFAP)
Description
Serum GFAP
Time Frame
3 years after Day 1
Title
Exploratory criteria: Pittsburgh Sleep Quality Index (PSQI) questionnaire
Description
Evaluation of habitual sleep quality trough a validated questionnaire. 19 items where each item is weighted on a 0-3 interval scale. The global PSQI score is then calculated by totaling the seven component scores, providing an overall score ranging from 0 to 21, where lower scores denote a healthier sleep quality.
Time Frame
3 years after Day 1
Title
Exploratory criteria: Idiopathic Hypersomnia Severity Hypersomnia Scale (IHSS)
Description
Patient-reported questionnaire assessing the severity of excessive sleepiness, prolonged sleep duration, cognitive impairment and sleep inertia. The total score ranges from 0 to 50, with higher scores indicating more severe symptoms.
Time Frame
3 years after Day 1
Title
Exploratory criteria: RU SATED score
Description
The Regularity, Sleep Quality, Alertness, Timing, Efficiency, Duration scale for sleep (RU SATED) ranges from 0 to 30, with higher scores indicating better sleep health.
Time Frame
3 years after Day 1
Title
Exploratory criteria: Insomnia Severity Index (ISI)
Description
The Insomnia Severity Index is a seven item-scale scored on a five-point scale (from 0 to 4). The total score ranges from 0 to 28. Higher scores indicate more insomnia.
Time Frame
3 years after Day 1
Title
Exploratory criteria: Headaches Impact Test (HIT-6)
Description
HIT-6 addresses six main domains affected by headaches, including pain, social functioning, role functioning, cognitive functioning, vitality and psychological stress. Little or no impact: 49 or less ; some impact: 50-55 ; substantial impact: 56-59 ; severe impact: 60-78
Time Frame
3 years after Day 1
Title
Exploratory criteria: Godin Leisure-Time Exercise Questionnaire (GLTEQ)
Description
Godin Leisure-Time Exercise Questionnaire (GLTEQ)
Time Frame
3 years after Day 1

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients over 18 and under 55 years of age Patients with Relapsing-remitting MS without relapse for at least 6 months EDSS<6 at time of inclusion Exclusion Criteria: Secondary progressive MS or Primary progressive MS at time of inclusion Evidence of disease progression (clinical or radiological) Change in treatment in the year prior to inclusion Subject with a contraindication to MRI (claustrophobia, pacemaker, etc.) Inability to follow the follow-up planned by the study Pregnant or breastfeeding women Patient not affiliated to the social security system or not benefiting from such a system Adult protected by law or patient under guardianship or curatorship Failure to obtain written informed consent after a reflection period
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xavier AYRIGNAC, Medical Doctor
Phone
0467337202
Email
x-ayrignac@chu-montpellier.fr
Facility Information:
Facility Name
Neurology Department, Hopital Gui de Chauliac
City
Montpellier
Country
France

12. IPD Sharing Statement

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Montpellier PROspective Cohort in Relapsing Remitting Multiple Sclerosis Using Imaging and Serologic

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