Clinical trial NCT06369766: REtinal Markers In Neuroinflammatory Diseases ("REMIND")
Official title: Retinal Markers in Neuroinflammatory Diseases: a Prospective Observational Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Multiple Sclerosis
Neuroinflammatory Diseases
Keywords: Retinal Markers
OCT
Disease Progression
Progression Independent of Relapse Activity (PIRA)
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
Collaborators: name: University of Basel
First posted: 2024-04-17
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with Multiple Sclerosis and the other neuroinflammatory diseases are recruited in the Multiple Sclerosis and Neuroimmunology center of the Department of Neurology at the University Hospital Basel in Basel. These patients with Multiple Sclerosis are participants of the ongoing observational Swiss Multiple Sclerosis Cohort Study. Healthy Controls are recruited from an older healthy control-cohort, which were matched to the Multiple Sclerosis patients and underwent Optical Coherence Tomography in 2016/2017. Further Healthy Controls are recruited bycontacting volunteers that participated in previous studies and agreed to be contacted again for new studies and by public announcements.

Brief summary: The goal of this observational study, including patients with Multiple Sclerosis, patients with other neuroinflammatory diseases and healthy controls, is to determine the predictive value of retinal markers in predicting disease progression. Participants complete a questionnaire and undergo various non-invasive retinal routine clinical examinations.

Detailed description: Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) and represents one of the most common neurological disorders affecting young adults worldwide and often leads to significant disability over time. While MS typically presents with recurrent neurological symptoms known as relapses, most patients also experience progressive neurological deterioration independent of relapses, referred to as progression independent of relapse activity (PIRA). PIRA is a major contributor to long-term disability and represents a significant challenge in the management of MS. Early identification of patients at high risk to develop PIRA is crucial for therapeutic decisions and testing treatment efficacy, highlighting the urgent need for accurate predictive markers of progression in MS.

The primary objective of this longitudinal, observational, prospective, single center study is to investigate the predictive value of various retinal markers in predicting PIRA in MS patients.

The study assesses several easily obtained, non-invasive retinal measures:

* Neuroaxonal loss in the retina: This serves as a marker of neurodegeneration in the CNS. It will be assessed by measuring the volume of the ganglion cell-inner plexiform layer and the thickness of the peripapillary retinal nerve fiber layer using optical coherence tomography (OCT).
* Neuroinflammation in the retina: This will be assessed by evaluating thickening of other retinal layers in OCT, particularly the inner nuclear layer.
* Fixation instability of the patients: This serves as a marker of global neuronal dysfunction in the CNS. It will be measured using Scanner Laser Ophthalmoscopy-OCT.
* Structural changes of the retinal vessels: Particularly, the arteriolar and venular diameters will be assessed. This serves as a marker of systemic microvascular health and will be measured using static retinal vessel analysis.
* Functional/perfusional changes of the retinal vessels: For a subgroup of patients, this will be evaluated using OCT-angiography, and/or dynamic retinal vessel analysis, and/or laser speckle flowgraphy. These measures provide insights into the functional and perfusional changes of the retinal vessels.

As secondary objectives, this study comprises:

* Comparison with other biomarkers of neuroaxonal damage to determine whether the retinal markers are independent and/or stronger predictors of PIRA.
* Comparison with the retinal markers of Healthy Controls and patients with other neuroinflammatory diseases of the CNS to understand the differences in mechanisms of damage.
* Investigating the associations among the various retinal measures to understand the relationship between neuroaxonal loss, functional deficits and vascular changes in MS.

Data will be collected at baseline and annually over up to 5 years, or for some MS patients, up to 10 years, to evaluate changes in retinal markers and their correlation with disease progression. This comprehensive assessment will provide valuable insights into the utility of retinal markers in predicting PIRA and their relationship with disease severity and progression in MS.

Eligibility criteria: Inclusion Criteria:

1. All groups:

   * Age \>18 years old
2. Patients with Multiple Sclerosis:

   * Diagnosis of Multiple Sclerosis, according to the last revisions of the McDonald Criteria (2017)
3. Patients with other neuroinflammatory diseases:

   * Diagnosis of Neuromyelitis optica spectrum disorder or Myelin oligodendrocyte glycoprotein antibody disease or other neuroinflammatory disorders other than Multiple Sclerosis

Exclusion Criteria:

1. All groups:

   * Inability to undergo Optical Coherence Tomography (OCT) and/or retinal vessel imaging (e.g. severe nystagmus that prevents eye fixation on both eyes)
   * Presence of any ocular pathology that may interfere with the validity of the OCT/retinal vessel analysis (cataracts, glaucoma, history of refractive defects \>6 D etc.).
   * Pregnancy and Lactation
2. Healthy Controls

   * History of other neurological conditions: participants with a history of other significant neurological conditions that might interfere with the assessment or interpretation of the signs and symptoms will be excluded (e.g. confirmed Stroke, Acute disseminated encephalomyelitis, Chronic inflammatory Demyelinating Disease, Polyneuropathy, etc.)

Primary outcomes:
measure: Occurence of Progression Independent of Relapse Activity (PIRA)
timeFrame: 5 Years (or for a subgroup up to 10 years) after baseline
measure: Neuroaxonal loss in the retina (as marker of neurodegeneration in the CNS)
timeFrame: Baseline and once every year over up to 5 years
measure: Neuroinflammation in the retina
timeFrame: Baseline and once every year over up to 5 years
measure: Fixation instability (as marker of global neuronal dysfunction in the CNS)
timeFrame: Baseline and once every year over up to 5 years
measure: Structural changes of the retinal vessels (as marker of systemic microvascular health)
timeFrame: Baseline and once every year over up to 5 years
measure: (For a subgroup of participants) Functional/perfusional changes of the retinal vessels
timeFrame: Baseline and once every year over up to 5 years
Secondary outcomes:
measure: Relative value of retinal markers for the prediction of PIRA compared to or combined with other biomarkers of neuroaxonal damage
timeFrame: Baseline and once every year over up to 5 years
measure: Comparison of the examined retinal markers of Multiple Sclerosis patients with Healthy Controls and with patients with other neuroinflammatory diseases of the CNS
timeFrame: Baseline and once every year over up to 5 years
measure: The relationship between neuroaxonal loss, functional deficits and vascular changes in Multiple Sclerosis
timeFrame: Baseline and once every year over up to 5 years
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel, Department of Neurology
Study officials:
affiliation: University Hospital Basel, Department of Neurology
name: Athina Papadopoulou, PD Dr. med.
role: PRINCIPAL_INVESTIGATOR
References: