Clinical trial NCT04979650: Corticosteroid Effects on Asymptomatic Gadolinium-enhancing Lesions in Multiple Sclerosis
Official title: Corticosteroid Pulse Therapy Effects on MRI Asymptomatic Gadolinium-enhancing Lesions Conversion to a Non-enhancing Black Hole With or Without Treatment in MS Clinic of Booalisina Hospital Sari 2021-2023
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Multiple Sclerosis, Relapsing-Remitting
Magnetic Resonance Imaging
Methylprednisolone
Keywords: Multiple sclerosis
Methylprednisolone Pulse therapy
Asymptomatic enhancing lesions
Chronic black hole
Lead sponsor: Mazandaran University of Medical Sciences
Sponsor class: OTHER
First posted: 2021-07-28
Enrollment: 104
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: to determine the rate of asymptomatic gadolinium-enhancing lesions conversion to the non-enhancing black hole (neBHs) with or without corticosteroid pulse therapy in patients with RRMS, and to analyze if treatment of asymptomatic gadolinium enhancement lesions has any effect on the expanded disability status scale. The study is performed in the MS clinic of Bu Ali Sina Hospital in Sari and Mazandaran University of Medical Sciences. 104 recurrent MS patients are admitted based on the admission criteria. They are divided into two groups of intervention and control based on a simple randomization block. The intervention group received 1 gram of methylprednisolone in 500 ccs of normal saline for 5 days and the control group received only 500 ccs of serum. After 6 months, a new MRI is taken from the patients and the possibility of asymptomatic active plaque conversion with or without intervention is compared in the two groups, as well as the amount of EDSS in the two groups. They do not know whether the patient is in the control group or the intervention.

Detailed description: Investigators perform a study on 104 consecutive patients with a diagnosis of RR-MS. Participants will be selected for the study if they meet all of the following inclusion criteria: (1) a baseline MRI scan with at least one CEL on contrast-enhanced T1-weighted images (performed either at the time of the diagnosis or during the routine MRI monitoring of the disease) and (2) a follow-up MRI scan performed at least 6 months later in the same hospital site. Participants were then divided into two groups by block randomization (the Block size will be 4): (1) participants with asymptomatic CELs, treated with a single cycle of high-dose IVMP after baseline MRI (group A) and (2) participants with asymptomatic CELs for clinical relapse and, therefore, not exposed to IVMP after baseline MRI (group B).

1. Microsoft Excel software will be used for block randomization with a group of 4.
2. Number the participants from 1 to 102.
3. In a group of 2, the possible combinations of blocks are:(A=Group1 and B=Group2)

1. ABBA 2. ABAB 3. BBAA 4. ABAB 5. BAAB 6. BABA

To determine the sample size for this study we used the result of Maria Di Gregorio and et al.

This study will be double-blind patients and radiologist clinicians unaware of types of interventions.

MRI examinations were performed with a 1.5 T magnet (General Electric Medical Systems, Milwaukee, WI, USA) with a standard head coil. The MRI protocol used in our Neuroradiology Section included the following sequences: (1) a T2-weighted-fluid-attenuated inversion recovery (FLAIR) sequence with an inversion time (TI) of 2400 ms, an echo time (TE) of 120 ms, and a repetition time (TR) of 8000 ms; (2) a T2-weighted fast spin-echo (FSE) sequence with a TE of 90 ms and a TR of 6600 ms; and (3) a spin-echo (SE) sequence for T1-weighted images with a TR of 500 ms and a TE of 20 ms Post-contrast images were obtained with a scan delay of 5 min after the injection of gadoterate (Dotarem, Guerbet group, Roissy, France) at 0.2 mmol/kg. 3-mm thick contiguous slices were obtained.

In the baseline MRI, the following characteristics of CELs were recorded: (1) number; (2) maximum diameter (≤ or \> 5 mm); (3) pattern of enhancement (homogeneous or ring enhancement); (4) hypointensity as compared to normal-appearing surrounding white matter in baseline T1-weighted images acute black hole (aBH); and (5) the fact of being symptomatic, as established by an experienced neurologist (MDG) on the basis of CELs' localization and clinical characteristics of the concomitant relapse. The follow-up MRI was performed with the same 1.5 T magnet and using the same MRI protocol. At the follow-up MRI, the presence of persistent black holes (pBHs) was recorded. Specifically, pBHs were defined as non-enhancing T1 lesions hypointense with respect to the surrounding normal-appearing white matter and concordant with hyperintense T2 lesions \[10\]. Three investigators (MDG, AP, and GR) in agreement with a senior experienced neuro-radiologist (PF) revised baseline CELs and follow-up pBHs' characteristics. The three investigators and the neuroradiologist were blinded to the exposure of the patients to IVMP treatment

Eligibility criteria: Inclusion Criteria:

* All patients with a diagnosis of RR-MS
* with a baseline MRI scan with at least one asymptomatic CEL on contrast-enhanced T1-weighted images

Exclusion Criteria:

* Pulse therapy 3 months ago,
* More than 6 months ago slowly progressive disease
* Systemic infections, including fungal infection
* Uncontrolled hypertension
* With known hypersensitivity to the steroid preparation

Primary outcomes:
measure: Number of black hole
timeFrame: After 6 months
measure: Expanded disability status scale
timeFrame: After 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Sari
country: Iran, Islamic Republic of
facility: Mazandaran University of medical sciences
state: Mazandaran
Study officials:
affiliation: Mazandaran University of Medical Sciences
name: Seyed Mohammad Baghbanian, Dr.
role: PRINCIPAL_INVESTIGATOR
References: