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

Multiple Sclerosis Clinical Trial

— PROMISE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05962177
• Other study ID #: RECHMPL20_0422
• Status: Recruiting
• Phase: N/A
• Start date: September 11, 2023
• Est. completion date: July 2028

Study information

• Verified date: November 2023
• Source: University Hospital, Montpellier
• Contact: Xavier AYRIGNAC, Medical Doctor
• Phone: 0467337202
• Email: x-ayrignac[@]chu-montpellier.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 400
• Est. completion date: July 2028
• Est. primary completion date: July 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Sclerosis

Intervention

Other:
• Magnetic Resonance Imaging
Magnetic Resonance Imaging
• Blood withdrawal
Blood withdrawal
• Neuropsychological tests
Neuropsychological tests

Locations

Country	Name	City	State
France	Neurology Department, Hopital Gui de Chauliac	Montpellier

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Montpellier

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total brain atrophy	Total brain atrophy measured with T1 MRI scans	3 years after Day 1
Secondary	Quantitative analysis: analysis of FLAIR hypersignals number	Analysis of FLAIR hypersignals numbers (lesion load)	3 years after Day 1
Secondary	Quantitative analysis: analysis of FLAIR hypersignals volume	Analysis of FLAIR hypersignals volume	3 years after Day 1
Secondary	Qualitative analysis: analysis of central vein lesions	Identification and quantification of central vein lesions on SWI	3 years after Day 1
Secondary	Qualitative analysis: analysis of peripheral rim lesion	Identification and quantification of peripheral rim lesions on SWI	3 years after Day 1
Secondary	Quantitative analysis: measurement of mean diffusivity	measurement of the mean diffusivity using diffusion tensor analysis	3 years after Day 1
Secondary	Quantitative analysis: measurement of anisotropy fraction	measurement of anisotropy fraction using diffusion tensor analysis	3 years after Day 1
Secondary	Quantitative analysis: measurement of cerebral blood flow (CBF)	cerebral blood flow analysis on 3DPCASL	3 years after Day 1
Secondary	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)	3 years after Day 1
Secondary	Clinical assessment scale: relapses	Clinical assessment scales (absolute changes and reaching threshold values): Relapses	3 years after Day 1
Secondary	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.	3 years after Day 1
Secondary	Clinical assessment scale: Computerized Speed Cognitive Test (CSCT)	" Computerized Speed Cognitive Test " (CSCT) provides screening for cognitive impairment in MS patients	3 years after Day 1
Secondary	Clinical assessment scale: Six-Minute Walk Test (6MWT)	Six-Minute Walk Test	3 years after Day 1
Secondary	Clinical assessment scale: 9-Hole Peg Test (9-HPT)	The 9-HPT is a brief, standardized, quantitative test of upper extremity function.	3 years after Day 1
Secondary	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.	3 years after Day 1
Secondary	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).	3 years after Day 1
Secondary	Quality of life scale: The Brief Pain Inventory (BPI)	The Brief Pain Inventory (BPI) assesses the severity of pain and its impact on functioning.	3 years after Day 1
Secondary	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.	3 years after Day 1
Secondary	Fatigue scale: Chalder Fatigue Scale	Chalder Fatigue Scale is a self-administered questionnaire for measuring the extent and severity of fatigue.	3 years after Day 1
Secondary	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.	3 years after Day 1
Secondary	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 .	3 years after Day 1
Secondary	Depression scale: Beck Depression Inventory (BID)	The Beck Depression Inventory (BDI) contains 21 items and identifies symptoms and attitudes associated with depression.	3 years after Day 1
Secondary	Anxiety scale: Generalized Anxiety Disorder 7-Item Scale (GAD-7)	Generalized Anxiety Disorder 7-Item Scale measures seven anxiety symptoms.	3 years after Day 1
Secondary	Headaches scale: ef-ID Migraine	ef-ID Migraine guide towards the diagnosis of migraine	3 years after Day 1
Secondary	Exploratory criteria:Serum Glial Fibrillary Acidic Protein (GFAP)	Serum GFAP	3 years after Day 1
Secondary	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.	3 years after Day 1
Secondary	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.	3 years after Day 1
Secondary	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.	3 years after Day 1
Secondary	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.	3 years after Day 1
Secondary	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	3 years after Day 1
Secondary	Exploratory criteria: Godin Leisure-Time Exercise Questionnaire (GLTEQ)	Godin Leisure-Time Exercise Questionnaire (GLTEQ)	3 years after Day 1