Neuromyelitis Optica
Conditions
Keywords
Neuromyelitis Optica, Cetirizine
Brief summary
Neuromyelitis optica (NMO) is an autoimmune disease that affects the central nervous system. Patients have relapses (also known as attacks) which are often quite severe and leave them with significant disability. Without treatment, within 5 years 50% of NMO patients are blind in one or both eyes or require walking assistance (cane, walker or wheelchair). NMO has only been relatively recently described and is fairly rare. Most NMO patients' immune systems produce abnormal antibodies against aquaporin-4 (AQP4), which is found in certain cells in the central nervous system. When these AQP4 antibodies bind to AQP4, they trigger a cascade of events involving the immune system which eventually leads to damage to the nervous system. This ultimately leads to disability, some of which is permanent. Until now, treatments for NMO have been mostly focused on decreasing production of this AQP4 antibody. However, recent experiments in animal models of NMO have shown the importance of what happens inside the central nervous system after the antibody binds to the nervous system cell. Specifically, researchers have noted the importance of a specific cell type, eosinophils, in causing damage in NMO lesions. In a recent study, researchers showed they could prevent damage from NMO by blocking eosinophils using cetirizine, which is a popular over-the-counter allergy medicine. Cetirizine is already known to be safe and well-tolerated in the general population. In this study, the researchers plan to add cetirizine on to patients' current NMO treatment. The researchers aim to show that it is safe, well-tolerated, and that with cetirizine, NMO patients have less relapses and therefore less disability over the course of the year following initiation of treatment. The researchers also plan to study how cetirizine changes the immunological profile in NMO patients by examining blood and cerebrospinal fluid.
Detailed description
The researchers hypothesize that cetirizine, an allergy medication that acts as an eosinophil-stabilizer, will decrease the relapse rate when added to current standard therapy in patients with neuromyelitis optica. Medication compliance will be assessed by the research coordinator at each visit through discussion with the patient and pill counting.
Interventions
DRUGcetirizine
Sponsors
Guthy Jackson Charitable Foundation
Icahn School of Medicine at Mount Sinai
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* 18 years to 85 * Meet criteria for the diagnosis of neuromyelitis optica as outlined by Wingerchuk et al in 2006. Alternatively patients may be included if they have had an episode of myelitis or optic neuritis in combination with a positive NMO IgG antibody, as positive antibody with a first episode is highly associated with future relapse. * Disease duration of at least 6 months * Stable, without any NMO relapses, for the 3 months prior to the baseline assessment visit * Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations.
Exclusion criteria
* Current therapy with daily cetirizine or another daily antihistamine for any indication * Known hypersensitivity to cetirizine, hydroxyzine, or any component of the formulation * Change in NMO disease-modifying therapy in the 3 months prior to baseline assessment * Pregnancy or planning pregnancy during the study period * Severe renal or hepatic impairment * Inability to complete the study protocol for any reason
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Annualized Relapse Rate Before Cetirizine | Baseline and 1 year | Relapses defined as patient-reported symptoms or objectively observed signs typical of an acute inflammatory demyelinating event in the CNS, with duration of at least 24 hours, in the absence of fever or infection. The on study ARR was calculated as the number of relapses during the study divided by the length of time in the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Epworth Sleepiness Scale | Baseline and 1 year | Sedation as measured by Epworth Sleepiness Scale. The test is a list of eight situations in which you rate your tendency to become sleepy on a scale of 0, no chance of dozing, to 3, high chance of dozing. Total score 0 to 24 from unlikelihood of abnormally sleep to excessively sleepy. |
| Expanded Disability Status Scale (EDSS) | Baseline and 1 year | Disability as measured by Expanded Disability Status Scale (EDSS). The EDSS provides a total score on a scale from 0 to 10, from normal function to lessening function with higher score, 10, being death due to MS. |
| Eotaxin Plasma Levels | 6 months | Eotaxin - an eosinophil-specific chemoattractant in the blood. Immunological measures related to eosinophil activity. Eotaxin plasma levels. |
Countries
United States
Participant flow
Recruitment details
Twenty-four potential participants were referred by treating physicians at the Corinne Goldsmith Dickinson Center for Multiple Sclerosis at Mount Sinai between April 2014 and February 2015. Sixteen were enrolled between Aprill 2014 and February 2016.
Participants by arm
| Arm | Count |
|---|---|
| Cetirizine 10mg oral each day | 16 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Cetirizine |
|---|---|
| Age, Continuous | 36.5 years |
| Age, Customized Age at Symptom onset | 31.0 years |
| Annualized Relapse Rate | 0.0 relapses per treatment year |
| Duration of Current Treatment | 18.3 months |
| Number of Previous Preventative NMO treatment types 0 | 10 Participants |
| Number of Previous Preventative NMO treatment types 1 | 5 Participants |
| Number of Previous Preventative NMO treatment types 2 | 1 Participants |
| Oral Prednisone use at Enrollment | 1 Participants |
| Positive NMO antibody in serum | 13 Participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 1 Participants |
| Total pre-study relapses | 3.0 relapses |
| Total pre-study relapses while on current preventative treatment | 0.0 relapses |
| Type of NMO Preventative Treatment at Enrollment Azathioprine | 1 Participants |
| Type of NMO Preventative Treatment at Enrollment Mycophenolate | 7 Participants |
| Type of NMO Preventative Treatment at Enrollment Rituximab | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 15 |
| other Total, other adverse events | 3 / 15 |
| serious Total, serious adverse events | 0 / 15 |
Outcome results
Primary
Annualized Relapse Rate Before Cetirizine
Relapses defined as patient-reported symptoms or objectively observed signs typical of an acute inflammatory demyelinating event in the CNS, with duration of at least 24 hours, in the absence of fever or infection. The on study ARR was calculated as the number of relapses during the study divided by the length of time in the study.
Time frame: Baseline and 1 year
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cetirizine | Annualized Relapse Rate Before Cetirizine | Baseline | 0.4 relapses per year | Standard Deviation 0.8 |
| Cetirizine | Annualized Relapse Rate Before Cetirizine | 1 year | 0.1 relapses per year | Standard Deviation 0.24 |
Secondary
Eotaxin Plasma Levels
Eotaxin - an eosinophil-specific chemoattractant in the blood. Immunological measures related to eosinophil activity. Eotaxin plasma levels.
Time frame: 6 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cetirizine | Eotaxin Plasma Levels | 19.25 pg/mL |
Secondary
Epworth Sleepiness Scale
Sedation as measured by Epworth Sleepiness Scale. The test is a list of eight situations in which you rate your tendency to become sleepy on a scale of 0, no chance of dozing, to 3, high chance of dozing. Total score 0 to 24 from unlikelihood of abnormally sleep to excessively sleepy.
Time frame: Baseline and 1 year
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cetirizine | Epworth Sleepiness Scale | Baseline | 6.5 units on a scale | Standard Deviation 5.33 |
| Cetirizine | Epworth Sleepiness Scale | 1 year | 6.9 units on a scale | Standard Deviation 4.5 |
Secondary
Expanded Disability Status Scale (EDSS)
Disability as measured by Expanded Disability Status Scale (EDSS). The EDSS provides a total score on a scale from 0 to 10, from normal function to lessening function with higher score, 10, being death due to MS.
Time frame: Baseline and 1 year
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cetirizine | Expanded Disability Status Scale (EDSS) | Baseline | 3.9 units on a scale | Standard Deviation 2.18 |
| Cetirizine | Expanded Disability Status Scale (EDSS) | 1 year | 3.2 units on a scale | Standard Deviation 2.31 |