Clemastine Fumarate as Remyelinating Treatment in Internuclear Ophthalmoparesis and Multiple Sclerosis...
Multiple SclerosisInternuclear OphthalmoplegiaRationale: Clemastine fumarate has been identified as potential remyelinating therapy for multiple sclerosis (MS). The (long-term) effects of clemastine need to be confirmed in clinical models for MS. Internuclear ophthalmoparesis (INO) may be used as a clinical model for investigating remyelinating therapies by measuring horizontal eye movements with infrared oculography. Furthermore, infrared oculography combined with a single dose of fampridine may be used to identify individuals with MS that are most likely to benefit from remyelinating therapy. Objective: To assess the (long-term) efficacy of clemastine fumarate in improving dysconjugacy of eye movements in patients with internuclear ophthalmoparesis and multiple sclerosis. Secondly, to assess whether a response to a single dose of fampridine can predict the effects of clemastine treatment. Study design: A single-centre double-blind randomized placebo-controlled trial consisting of a 6 months (180 days) treatment period followed by a 30 months follow-up period. Study population: 80 MS patients, age 18-70 years, with INO. Intervention: The intervention group will receive 4 mg of clemastine fumarate twice daily (8 mg/day) for 6 months (180 days), the control group will receive an equivalent amount of placebo. At baseline all participants will receive a single 10 mg dose of fampridine. Main study parameters/endpoints: The primary outcome measure is the change in versional dysconjugacy index (VDI) of area under the curve (AUC) measured by infrared oculography. Secondary outcome measures include changes in other VDI measures (peak velocity per amplitude (PV/Am) and peak velocity (PV)), changes in VDI after single fampridine dose, other oculography parameters (e.g. saccadic latency, anti-saccades), (peripheral) retinal nerve fibre layer (pRNFL) and (macular) ganglion cell inner plexiform layer (mGCIPL) thickness measured by OCT, SDMT, EDSS, high and low contrast visual acuity, subjective visual functioning (NEI-VFQ-25 and NOV-AU questionnaire), quality of life (EQ5D-5L) and fatigue (CIS20R and NFI-MS questionnaire). Nature and extent of the burden and risks: Participation in the study will consist of a total of 7 study visits. Study visits will include physical/neurological examination, infrared oculography, OCT, visual acuity tests, a cognition test (SDMT), 5 questionnaires and blood samples for safety laboratory tests. Considering both clemastine and fampridine are registered and well-established drugs and have been used in clinical practice, the estimated risk of unexpected adverse reactions is low.
Clinical Trial Comparing Two Non-Surgical Treatments for Severe Blepharoptosis
BlepharoptosisPtosis5 moreThis clinical trial will evaluate two non-surgical devices designed to improve eye lid opening for patients with severe Blepharoptosis (incomplete opening of the eyelids).
The KHENEREXT Study
Mitochondrial DiseasesMitochondrial DNA tRNALeu(UUR) m.3243A<G Mutation4 moreThis is an open-label, multi-centre study in subjects with a genetically confirmed mitochondrial deoxyribonucleic acid (DNA) transfer ribonucleic acid (tRNA)Leu(UUR) m.3243A>G mutation who completed study KH176-202. In the KH176-203 study subjects will be receiving KH176 100 mg BID or KH176 50 mg bid in die (BID) (as determined by the investigator based on safety / tolerability considerations) for a year, thereby ensuring continued treatment with KH176 after study KH176-202. A final follow-up visit is scheduled 4 weeks after the intake of the last dose of study medication for patients not rolling over into the compassionate use program. Primary safety data and secondary efficacy (endpoint) data will be monitored and reviewed every three months by an independent Data Safety Monitoring Board (DSMB) to evaluate potential risks and benefits.
Genomic Profiling of Mitochondrial Disease - Imaging Analysis for Precise Mitochondrial Medicine...
Mitochondrial MyopathiesMitochondrial DNA Mutation3 moreThis study is an observational longitudinal study involving the use of MRIs and video recordings taken at home of patients completing basic tasks. Once consent is obtained, subjects will be asked to schedule an appointment with radiology to undergo the listed MRIs of the heart and/or muscle. Subjects will also be given instructions on how to use the video recording app on their personal devices, or study provided device. The subjects will be followed regularly over the course of two years, submitting video recordings of their movements and reporting to Mayo Clinic for MRIs as scheduled.
Genetic Studies of Strabismus, Congenital Cranial Dysinnervation Disorders (CCDDs), and Their Associated...
Congenital Fibrosis of Extraocular MusclesDuane Retraction Syndrome26 moreThe purpose of this study is to identify genes associated with impaired development and function of the cranial nerves and brainstem, which may result in misalignment of the eyes (strabismus) and related conditions.
Capsular Tension Rings in Intraocular Lens Rotation
CataractOphthalmoplegia1 moreTo investigate whether implantation of a capsular tension ring device will affect the degree of rotation of an implanted toric intraocular lens following cataract surgery.
Nicotinamide Riboside and Mitochondrial Biogenesis
Mitochondrial DiseasesMitochondrial Myopathies6 moreMitochondria are important parts of the cell that are responsible for producing energy. The amount of energy they produce depends on how much energy the body needs to function and this energy production can be severely impaired in people with mitochondrial disease. Symptoms of mitochondrial disease vary widely but usually involve the brain, nerves and muscles, as these are tissues that need a lot of energy. Mitochondrial disorders affect 1 in 5000 of the UK population and there is currently no cure. Some scientists think that increasing the number of mitochondria in the body (mitochondrial biogenesis) might be an effective treatment for the symptoms of mitochondrial disease. Studies carried out in mice have shown that a type of B-vitamin called Nicotinamide Riboside (NR) is able to increase the number of mitochondria, leading to increased energy and a reduction in the symptoms of mitochondrial disease. The aim of this study is to investigate if the same B vitamin, Nicotinamide Riboside, can increase energy production and reduce symptoms in humans with mitochondrial disease. The study will consist of two parts: Part 1: Participants will be given a single oral dose of Nicotinamide Riboside and the levels of NR in their bloodstream will be measured at regular intervals. This will involve a single overnight stay and simple blood tests. Part 2: This requires 6 separate visits from each participant. Each participant will undergo a series of standard tests including a muscle biopsy and an MRI scan, then they will take a course of Nicotinamide Riboside (twice daily for 4 weeks). After 4 weeks of treatment, the participants will undergo the same tests again to see if there have been any changes in response to the treatment.
Study and Treatment of Visual Dysfunction and Motor Fatigue in Multiple Sclerosis
Multiple SclerosisInternuclear Ophthalmoplegia1 morePrimary fatigue represents a major cause of disability in patients with multiple sclerosis (MS), being reported in about 90% of cases. Fatigue interferes with everyday functioning but, unfortunately, little is known about its mechanisms. The investigators propose a characteristic eye movement abnormality (internuclear ophthalmoparesis, INO), commonly encountered in MS, as a simple model for primary motor fatigue. The investigators described worsening of ocular performance in MS patients with INO following visual tasks (ocular motor fatigue), which is likely due to decreased neural conduction along brain pathways injured by MS. This mechanism could represent a major component of MS-related primary motor fatigue. Relevant to Veterans' care, INO is a significant cause of visual disability, especially when complicated by ocular fatigue, and limits daily activities such as reading and driving. The investigators propose a medical treatment to improve ocular performance/fatigue in INO, which can reduce visual disability and improve quality of life in Veterans with MS.
Prevalence of a High-intensity Signal of the Oculomotor Nerve on T2 MRI Sequence in Patients With...
OphthalmoplegiaOculomotor nerve (third cranial nerve or III) palsy is a relatively frequent cause of consultation in ophthalmology. It may reveal a life-threatening pathology such as aneurysm rupture, pituitary apoplexy, and therefore need imaging in emergency. Apart from few extreme emergency situations, MRI of the oculomotor tract is the first-line examination required. In the usual clinical practice, the investigators noticed in several patients unusual areas of high-intensity signal within the oculomotor nerve on T2 sequence, observed in various locations along the nerve path (cavernous and/ or intra-orbital segment). This abnormal signal, at the best knowledge of the investigators, has never been reported in the literature and could confirm the nerve impairment. In patients with ophthalmoplegia involving probably the third cranial nerve, disclosing this new MRI sign could help (i) to confirm the involvement of the oculomotor nerve and eliminate differential diagnoses such as myasthenia (ii) to orientate the etiological diagnosis (inflammatory or ischemic origin). A T2 sequence focused on the III could thus be systematically included in the usual MRI protocol.
Prevalence of Contrast Enhancement of the Oculomotor Nerve on 3D PD T1 MRI Sequence in Patients...
OphthalmoplegiaOculomotor nerve (third cranial nerve or "III") palsy is a relatively frequent cause of consultation in ophthalmology. It may reveal a life-threatening pathology such as aneurysm rupture, pituitary apoplexy, and therefore need imaging in emergency. Apart from few extreme emergency situations, MRI of the oculomotor tract is the first-line examination required. In our usual clinical practice, we noticed in several patients unusual contrast enhancement within the oculomotor nerve on T1 sequence with gadolinium injection, observed in various locations along the nerve path (cavernous and/ or intra-orbital segment). This contrast enhancement, could confirm the nerve impairment This study aims to analyse the efficiency of a new sequence 3D PD T1 which isotropic spatial resolution less than 1mm, not yet described in the literature, to depict this enhancement. In patients with ophthalmoplegia involving probably the third cranial nerve, disclosing this MRI sign could help (i) to confirm the involvement of the oculomotor nerve and eliminate differential diagnoses such as myasthenia (ii) to orientate the etiological diagnosis (inflammatory or ischemic origin). This new sequence 3D PD T1 sequence focused on the III could thus be systematically included in the usual MRI protocol.