Clinical trial NCT05407428: A Prospective Study to Evaluate the Correlation Between Oculometric Measurements and Clinical Endpoints in ALS Patients
Official title: An Prospective Study in a Cohort of Amyotrophic Lateral Sclerosis (ALS) Patients Participating in a Phase IIb Drug Study (NCT05357950) to Evaluate the Correlation Between Oculometric Measurements and ALS Functional Rating Scale (ALSFRS-R)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Amyotrophic Lateral Sclerosis
Lead sponsor: NeuraLight
Sponsor class: INDUSTRY
First posted: 2022-06-07
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: About 45 ALS patients, ages 18-75 years with familial or sporadic ALS, according to the Gold Coast Criteria, who are recruited and participating in the PrimeC drug study (NCT05357950)

Brief summary: This is a prospective study in a cohort of about 45 patients with ALS participating in the Neurosense PrimeC drug study (NCT05357950).

This study aims to evaluate the correlation between oculometric measures and clinical endpoints. Subjects will be evaluated every 2 months during a time period of 18 months. The evaluations will include ALSFRS-R examination, as well as an oculometric evaluation for eye movements.

Detailed description: This is an observational prospective study in a cohort of about 45 patients with ALS participating in the Neurosense PrimeC drug study (NCT05357950), which is a Phase IIb, Randomized, Prospective, Double-Blind, Placebo-Controlled Study, to Evaluate Safety, Tolerability and Efficacy of PrimeC in Subjects with ALS. The subjects are males or females with familial or sporadic ALS of no more than 30 months disease duration, who meet the inclusion criteria of the PrimeC drug study, provide a signed an Informed consent and are willing and able to comply with study's procedures including follow-up visits.

This study is designed to evaluate the correlation between oculometric measures and the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R). Subjects will be evaluated every 2 months during a time period of 18 months. The evaluations will include an ALSFRS-R examination by a certified neurologist and other tests. In addition, all patients will undergo a NeuraLight session for oculometric evaluation along with eye-tracking recordings. All assessments will be performed during a clinic visit unless authorized to be conducted remotely.

Eligibility criteria: Inclusion Criteria:

* Able to comprehend and willing to sign an informed consent form (ICF)
* Males or females between the ages of 18 and 75 years of age, inclusive
* Diagnosis of familial or sporadic ALS (defined as meeting the laboratory-supported probable, probable, or definite criteria for a diagnosis of ALS according to the Gold Coast criteria)
* Disease duration after first symptom (muscle weakness) less than 30 months prior to screening
* Pre-enrollment ALSFRS-R slope from disease onset ≥ 0.3 points per month
* ALSFRS-R at screening ≥ 25
* Item 3 (swallowing) in ALSFRS-R ≥ 3
* Subjects may be treated in parallel with Riluzole and/or Edaravone and/or Sodium Phenylbutyrate; 30 days of stable use prior to enrollment is required
* Upright slow vital capacity (SVC) ≥ 60% of predicted for age, height, weight and sex at screening according to the GLI-2012
* 18 \< BMI \< 30
* A caregiver (if one is needed)
* Female subjects must be post-menopausal (≥ 1 year) OR sterilized, OR if of childbearing potential (i.e., females who have had their first period unless they are anatomically or physiologically incapable to become pregnant), must have a negative pregnancy test, and agree to use contraceptive drugs or devices (e.g., diaphragm plus spermicide, or oral contraceptives) for the duration of the study and 10 weeks after the last treatment dose AND require male partners to use a condom during sexual intercourse

Exclusion Criteria:

* A past history of adverse reaction/hypersensitivity to either NSAIDs, celecoxib or fluoroquinolones, ciprofloxacin
* Any known clinically significant abnormal gastric mucosal erosion, ulcer or tumor or/and GI disorder and/or bariatric surgery Known history of clinically significant impairment of renal function (creatinine ≥ 1.5)
* Known or suspected symptomatic congestive heart and/or coronary heart disease, previous history of myocardial infarction, uncontrolled arterial hypertension, or rhythm abnormalities requiring permanent treatment
* Known history of QT/QTc prolongation, Torsade de pointes (TdP) (e.g. heart failure, hypokalemia, family history of Long QT syndrome) and the use of concomitant medications that prolong the QT/QTc interval
* Known or suspected diagnosis or family history of epilepsy in first degree relatives
* Known predisposition to tendinitis
* Tracheostomy or percutaneous gastrostomy use
* Presence at screening of any medically significant cardiac, pulmonary, musculoskeletal, or psychiatric illness that might interfere with the subject's ability to comply with study procedures or that might confound the interpretation of clinical safety data, including, but not limited to:

  1. Mean systolic blood pressure \>160 mm Hg and/or mean diastolic blood pressure \>100 mm Hg (measurements taken after a few minutes rest) that persist on 3 successive measurements taken at least 2 minutes apart
  2. NYHA Class II or greater congestive heart failure
  3. Chronic obstructive pulmonary disease or asthma requiring daily use of bronchodilator medications
  4. Poorly controlled or brittle diabetes mellitus
  5. Cognitive impairment, related to ALS or otherwise, sufficient to impair subject's ability to understand and/or comply with study procedures and provide informed consent
* Subject who is treated with chronic aspirin or NSAIDs and is at risk if stopped. Clopidogrel is allowed and can replace Aspirin.
* Any contraindication for ciprofloxacin and celecoxib according to the current prescribing information.
* Female who is pregnant or breastfeeding or with intention of becoming pregnant during the course of the study.
* Any impairment or social circumstance that, in the opinion of the Investigator, would render the subject not suitable to participate in the study.
* Subject, or subject's legal guardian(s) is/are unable to understand the nature, scope, and possible consequences of the study.
* Subject is participating in (or plans to participate in) any other investigational drug trial, or plans to be exposed to any other investigational agent, device and/or procedure, from 30 days prior to Screening through study completion.

Primary outcomes:
measure: Correlation between ALSFRS-R score and its parts with NeuraLight oculometric measurements
timeFrame: 18 months
measure: Feasibility of using NeuraLight system to capture oculometric measures in a cohort of ALS patients
timeFrame: 18 months
measure: Comparison of NeuraLight extracted oculometric measures with a validated eye-tracking system
timeFrame: 18 months
Secondary outcomes:
measure: Using the retrieved data of collected NeuraLight oculometric measures for calibration of prediction models of ALSFRS-R clinical endpoint
timeFrame: 18 months
Other outcomes:
Locations:
city: Tel Aviv
country: Israel
facility: Sourasky medical center
Study officials:
affiliation: Sackler Faculty of Medicine, Tel Aviv University
name: Vivian Drory, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kang BH, Kim JI, Lim YM, Kim KK. Abnormal Oculomotor Functions in Amyotrophic Lateral Sclerosis. J Clin Neurol. 2018 Oct;14(4):464-471. doi: 10.3988/jcn.2018.14.4.464. Epub 2018 Jun 27.
citation: Guo X, Liu X, Ye S, Liu X, Yang X, Fan D. Eye Movement Abnormalities in Amyotrophic Lateral Sclerosis. Brain Sci. 2022 Apr 11;12(4):489. doi: 10.3390/brainsci12040489.