Neuromyelitis Optica (NMO) & Cetirizine

An Open Label, add-on Trial of Cetirizine for Patients With Neuromyelitis Optica

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.

Study Overview

• Status: Completed
• Conditions: Neuromyelitis Optica
• Intervention / Treatment: Drug: cetirizine

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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: cetirizine; 10mg oral each day	Drug: cetirizine; Other Names: Zyrtec

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline and 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline and 1 year
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.	Baseline and 1 year
Eotaxin Plasma Levels	Eotaxin - an eosinophil-specific chemoattractant in the blood. Immunological measures related to eosinophil activity. Eotaxin plasma levels.	6 months

Collaborators and Investigators

• Sponsor: Icahn School of Medicine at Mount Sinai
• Collaborators: Guthy Jackson Charitable Foundation
• Investigators: Principal Investigator: Ilana Katz Sand, MD, Icahn School of Medicine at Mount Sinai

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): February 1, 2016
• Study Completion (Actual): February 1, 2016

Study Registration Dates

• First Submitted: August 9, 2016
• First Submitted That Met QC Criteria: August 9, 2016
• First Posted (Estimated): August 12, 2016

Study Record Updates

• Last Update Posted (Actual): June 7, 2023
• Last Update Submitted That Met QC Criteria: May 11, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Cetirizine; Neuromyelitis Optica
• Additional Relevant MeSH Terms: Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Eye Diseases; Optic Nerve Diseases; Cranial Nerve Diseases; Myelitis, Transverse; Optic Neuritis; Neuromyelitis Optica; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Allergic Agents; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Histamine H1 Antagonists, Non-Sedating; Cetirizine
• Other Study ID Numbers: 13-1513

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO