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Efficacy of Lenses in Abolishing Photoparoxysmal Responses (PPRs)

Primary Purpose

Reflex Epilepsy, Photosensitive, Eyeglasses

Status
Recruiting
Phase
Not Applicable
Locations
United Kingdom
Study Type
Interventional
Intervention
Z1 lens
Experimental Lens 1
Experimental Lens 2
Experimental Lens 3
Experimental Lens 4
Sponsored by
Aston University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Reflex Epilepsy, Photosensitive focused on measuring photosensitivity, pattern sensitivity, Electroencephalography, Photic Stimulation, Pattern Stimulation, photoparoxysmal response, Light, Visible, Red Colour, Blue Light, children, epilepsy, standardized photoparoxysmal response range

Eligibility Criteria

5 Years - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers
  1. Inclusion Criteria:

    1. Children and adolescents between 5-18 years with suspected or confirmed diagnosis of photosensitive epilepsy (PSE), whether they are taking antiepileptic medication or not.
    2. Capacity to:

      • maintain concentration during the procedure
      • follow simple commands
      • assent (under 16 years) or consent (16-18 years) to participate after understanding the purpose of the study.
  2. Exclusion Criteria:

    1. Presence of a condition that may compromise the ability to tolerate the procedure and/or the capacity to assent or consent, such as:

      • intellectual disability
      • attention-deficit/hyperactivity disorder
      • autism spectrum disorders
      • difficulties to understand verbal/written explanations in English
    2. Refusal to participate
    3. Generalized seizure during the EEG procedure.
    4. Female patients suspected or known to be pregnant.

Sites / Locations

  • Birmingham Women's and Children's NHS Foundation TrustRecruiting
  • Aston UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

5 Lenses

Arm Description

The five lenses will be tested in each patient following always the same specific order, with the most protective lenses tested first (Z1). Z1F133 (Zeiss Clarlet Z1) is a CE marked device manufactured by Carl Zeiss Vision International GmBH (Aalen, Germany). Our lenses are CE marked devices manufactured by Cerium Optical Products (Kent, UK).

Outcomes

Primary Outcome Measures

PPR change
Relative change in the photoparoxysmal response grade
SPR change
Relative change in the standardized photoparoxysmal response range (SPR)

Secondary Outcome Measures

Adherence and tolerability to lenses in everyday life
The score obtained in the different sections of the Patient Satisfaction Questionnaire [on a scale from 1 (worst outcome) to 5 (best outcome)]

Full Information

First Posted
August 30, 2019
Last Updated
July 25, 2022
Sponsor
Aston University
Collaborators
Birmingham Women's and Children's NHS Foundation Trust
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1. Study Identification

Unique Protocol Identification Number
NCT04076410
Brief Title
Efficacy of Lenses in Abolishing Photoparoxysmal Responses
Acronym
PPRs
Official Title
Efficacy of New Lenses in Abolishing Photoparoxysmal Responses in Paediatric Patients With Photosensitive Epilepsy (PSE)
Study Type
Interventional

2. Study Status

Record Verification Date
July 2022
Overall Recruitment Status
Recruiting
Study Start Date
February 20, 2021 (Actual)
Primary Completion Date
January 31, 2024 (Anticipated)
Study Completion Date
January 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Aston University
Collaborators
Birmingham Women's and Children's NHS Foundation Trust

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Background. Blue lenses that filter out red light have been proposed as a new therapeutic alternative for patients with PSE, such as the lens Zeiss Clarlet Z1. This lens only allows a small overall quantity of visible light, and particularly a minimum percentage of red light, to pass through. However, these characteristics entail two main pitfalls: reduced applicability in high- latitude regions and lack of transmission for the red and yellow colors. The latter would mainly expose patients to the other colors that compose the visible light, and particularly to the blue visible light. This exposure might be damaging for their eyes in the long term, as it has been reported in some studies. Aim. To determine whether four new lenses with different spectral characteristics are not inferior in efficacy to Z1 to reduce the PPRs in patients with PSE. Participants. Patients between 5-18 years with suspected or confirmed PSE, referred to the Neurophysiology Service at Birmingham Children's Hospital (BCH) for an EEG with IPS/pattern stimulation. Objectives & Outcomes: 1.A) Primary Objective: To evaluate the reduction/suppression produced by four new lenses in the PPRs shown by patients with PSE during an EEG with IPS/pattern stimulation, and compare it with the reduction provoked by the Z1 lens in the same individuals. B) Primary Outcome: reduction/suppression in both the PPR and the standardized photoparoxysmal response range (SPR) for IPS and pattern stimulation. A) Secondary Objectives: To obtain feedback from the patients who acquire a pair of our lenses regarding tolerability, overall adherence to treatment and improvement in the quality of life. Comparison of the reduction/suppression in the PPRs between our lenses and the Z1 lens in those retrospective patients with PSE seen between 2008-2017 at the Aston Brain Center. 2.B) Secondary Outcomes: Mean score obtained in adherence to treatment, tolerability, reduction in seizure frequency and autonomy according to the patient/parents or carers satisfaction questionnaires. Reduction/suppression in both the PPR and the standardized photoparoxysmal response range (SPR) for IPS and pattern stimulation in those patients recruited at the Aston Brain Center.
Detailed Description
BACKGROUND Photosensitive epilepsy (PSE) is the most common of reflex epilepsies and represents approximately 10% of all new cases of epilepsy in the age range 7-19 years (Harding & Jeavons, 1994). Photosensitivity is the nuclear feature of PSE, in which seizures are provoked by light stimuli or visual patterns, such as lines, gratings or checkerboards (Yalçin, Kaymaz, & Forta, 2000)(Fisher, Harding, Erba, Barkley, & Wilkins, 2005). Therefore, usual external triggers of seizures in the daily life of patients with PSE are sunlight and screens, like televisions (TVs), video games and computer displays. Photic/pattern sensitivity can be detected on the electroencephalogram (EEG) by the presence of a specific abnormality, called the 'photoparoxysmal response' (PPR), which is usually evoked by intermittent photic stimulation (IPS) or pattern stimulation, respectively (Quirk et al., 1995). Red color (wavelength around 600-700nm) has been proposed to be the most provocative stimulus among the primary colors to trigger photosensitivity/pattern-sensitivity in these patients (Fisher et al., 2005)(Guerrini & Genton, 2004). There are certain preventive measures to avoid triggering external stimuli which are particularly useful in PSE patients, but pharmacological treatment is required when seizures are not controlled by preventive measures or when photic or pattern-induced seizures coexist with spontaneous seizures. However, adverse effects of antiepileptic drugs (AEDs) and the relapse percentage after medication withdrawal, which may be nearly 50% (Verrotti et al., 2014), drove investigators to seek other therapeutic alternatives, such as the use of blue lenses that filter out red light. To date, the most extensively investigated lens has been Zeiss Clarlet Z1, which abolished PPRs in 75.9% of 610 patients (Giuseppe Capovilla et al., 2006). This effect was accounted for by the spectroscopic profile of Z1, that shows the minimal transmittance for the spectrum of red color (600-700 nm) (G Capovilla et al., 1999) and a luminous transmittance for the visible spectrum (τν) around 7%. However, Z1 transmittance characteristics have two main limitations for its use in everyday life: 1) it is a very dark lens and not practical in high-latitude regions, where the number of sunlight hours is reduced; 2) its lack of transmission in the red and yellow parts of the spectrum determines that people using Z1 are almost completely exposed to blue visible light, which has been associated with the appearance of ophthalmological diseases in the long term, such as age-related macular degeneration (AMD) ("blue-light hazard" phenomenon) (Mainster, 2006). RATIONALE In light of these limitations, we hypothesized that a new type of lenses created by improving some spectral characteristics of Z1 could also be helpful for patients with PSE. This is the reason why we have designed four new lenses at the Aston Brain Center (ABC, Aston University) in collaboration with the Aston University Vision Sciences Department. These new lenses were firstly tested in those patients with PSE referred to the ABC between 2008-2017, when this center was the referral site in West Midlands to perform an EEG with photic/pattern stimulation. To date, no lens has demonstrated similar efficacy to Z1 with improved transmittance characteristics. Our new lenses may become an alternative or adjuvant therapy for paediatric and adult patients with PSE, leading to a reduction in the necessary dose of medication, with consequently less probability of adverse effects and an overall improvement in the quality of life. AIM AND OBJECTIVES The aim of our study is to demonstrate that our lenses are not inferior in efficacy to reduce the PPRs in comparison with Z1 in a sample of children and adolescents with PSE. The primary objective of this study is to investigate the efficacy of these four lenses in suppressing the PPRs evoked by IPS and/or pattern stimulation in a sample of pediatric patients with PSE recruited at the Birmingham Women's and Children's NHS Foundation Trust (BWCH), and compare their results with those obtained with Z1 in the same patient. Our secondary objectives are: To collect the retrospective information (clinical and EEG data) of those PSE patients who were seen between 2008 and 2017 at the ABC, where the lenses were firstly tested before moving the equipment to the BWCH. To obtain feedback from the patients who finally acquire a pair of our lenses in relation to the overall adherence to treatment, tolerability and improvement in the quality of life. To achieve this objective, we will send a patient satisfaction questionnaire (PSQ) to these patients approximately 6 months after purchasing the lenses. 4. DESIGN This is a single-arm clinical trial. We will carry out two types of study: a prospective (forward) study recruiting patients at BWCH and also a retrospective (backwards) study collecting those patients seen at the ABC between 2008 and 2017. In both studies, data analysis will take place at Aston University after being pseudonymized. 5. METHODS 5.1. Recruitment Prospective study (BWCH, Aston University): Patients (either males or females) from 5 to 18 years with suspected or confirmed diagnosis of generalised epilepsy with photosensitivity or photosensitive epilepsy (PSE) who are referred to the Neurophysiology Service at BCH for an EEG with IPS/pattern stimulation to confirm the diagnosis or check evolution, whether they are taking AEDs or not. Participants will be able to maintain concentration during the procedure, follow simple commands given by the NHS PI and have the capacity to assent (under 16 years) or consent (16-18 years) to participate after checking that they have understood the purpose of the study. Retrospective study (Aston University): •Selection criteria followed in the retrospective study conducted at the ABC were the same, except for the age criterion, since adult patients were also seen at the ABC. 5.2. Trial Procedures Prospective study (BWCH, Aston University): On the first visit to the BWCH, a standardised procedure for EEG with IPS (Kasteleijn-Nolst Trenité et al., 2012) will be performed, followed by stimulation with visual patterns (stationary vertical grids at different spatial frequencies on a screen). If PPRs are shown in response to IPS/pattern stimulation, lenses will be tested to evaluate the relative reduction produced by our lenses & Z1 on the PPRs evoked by IPS/pattern testing. This reduction will be determined by the change in both the type of PPR and the standardized photoparoxysmal response range (SPR). If our lenses are effective and patients/families decide to acquire one of them, they will be asked to fill in a Likert-scale PSQ approximately 6 months after purchasing the lenses. This information will provide us with some feedback on the overall adherence to treatment, tolerability and improvement in the quality of life. 5.2.2) Retrospective study (Aston University): it will consist in the same procedures as the prospective study, but in this case the PSQ was not sent to patients/families. 6. DATA ANALYSIS A minimum sample size of 76 patients was obtained based upon data collected from a previous pilot study, taking into consideration a power value of 80%, an alpha value of 5% and a non-inferiority margin of 0.03. For each patient, we will compare the reduction/suppression on both the PPR and the SPR between the different lenses (α=0.05). PSQ results will be expressed by the percentages of patients/parents who marked a particular response in these multiple-choice questionnaires. Missed data (patients who finally drop out of the study) will not be considered for analysis purposes. 7. ETHICAL CONSIDERATIONS All procedures conducted will comply with the Declaration of Helsinki as revised in 2013, the Data Protection Act 1998 and Local Information Governance protocols. Consent will be sought from parents/legal guardians and patients over 15 years, as well as assent in the case of younger patients. Only pseudonymized raw data will be available for sharing outside of the department as the analysis is to be performed by the PI-based at the sponsor site (Aston University). Data storage will be in keeping with the Trust Information Governance policies.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Reflex Epilepsy, Photosensitive, Eyeglasses
Keywords
photosensitivity, pattern sensitivity, Electroencephalography, Photic Stimulation, Pattern Stimulation, photoparoxysmal response, Light, Visible, Red Colour, Blue Light, children, epilepsy, standardized photoparoxysmal response range

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
Participants will be recruited among those patients (both males and females) from 5 to 18 years with suspected or confirmed diagnosis of generalised epilepsy with photosensitivity or photosensitive epilepsy (PSE) who comply with the established inclusion criteria. No control patients will be required, since each patient will be tested with the different lenses in a specific order and will be, in turn, his/her own control. No randomisation will be carried out in our study.
Masking
None (Open Label)
Allocation
N/A
Enrollment
76 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
5 Lenses
Arm Type
Experimental
Arm Description
The five lenses will be tested in each patient following always the same specific order, with the most protective lenses tested first (Z1). Z1F133 (Zeiss Clarlet Z1) is a CE marked device manufactured by Carl Zeiss Vision International GmBH (Aalen, Germany). Our lenses are CE marked devices manufactured by Cerium Optical Products (Kent, UK).
Intervention Type
Device
Intervention Name(s)
Z1 lens
Other Intervention Name(s)
Zeiss F133
Intervention Description
CE marked device
Intervention Type
Device
Intervention Name(s)
Experimental Lens 1
Intervention Description
CE marked device
Intervention Type
Device
Intervention Name(s)
Experimental Lens 2
Intervention Description
CE marked device
Intervention Type
Device
Intervention Name(s)
Experimental Lens 3
Intervention Description
CE marked device
Intervention Type
Device
Intervention Name(s)
Experimental Lens 4
Intervention Description
CE marked device
Primary Outcome Measure Information:
Title
PPR change
Description
Relative change in the photoparoxysmal response grade
Time Frame
Baseline (First visit T0)
Title
SPR change
Description
Relative change in the standardized photoparoxysmal response range (SPR)
Time Frame
Baseline (First visit T0)
Secondary Outcome Measure Information:
Title
Adherence and tolerability to lenses in everyday life
Description
The score obtained in the different sections of the Patient Satisfaction Questionnaire [on a scale from 1 (worst outcome) to 5 (best outcome)]
Time Frame
6 months after acquiring the lenses (T6)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
5 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Children and adolescents between 5-18 years with suspected or confirmed diagnosis of photosensitive epilepsy (PSE), whether they are taking antiepileptic medication or not. Capacity to: maintain concentration during the procedure follow simple commands assent (under 16 years) or consent (16-18 years) to participate after understanding the purpose of the study. Exclusion Criteria: Presence of a condition that may compromise the ability to tolerate the procedure and/or the capacity to assent or consent, such as: intellectual disability attention-deficit/hyperactivity disorder autism spectrum disorders difficulties to understand verbal/written explanations in English Refusal to participate Generalized seizure during the EEG procedure. Female patients suspected or known to be pregnant.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Stefano Seri, Prof
Phone
+44 (0)121 333
Ext
9260
Email
s.seri@nhs.net
First Name & Middle Initial & Last Name or Official Title & Degree
Peter R Bill, CSci
Phone
+44 (0)121 333
Ext
9264
Email
peter.bill@nhs.net
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bryony Carr, BSc
Organizational Affiliation
Birmingham Women's and Children's NHS Foundation Trust
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ana Checa-Ros, MD, PhD
Organizational Affiliation
Aston University, Birmingham, UK
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Sukhvir Wright, MD, PhD
Organizational Affiliation
Aston University
Official's Role
Study Chair
Facility Information:
Facility Name
Birmingham Women's and Children's NHS Foundation Trust
City
Birmingham
State/Province
West Midlands
ZIP/Postal Code
B4 6NH
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Stefano Seri, Prof
Phone
+44 (0)121 333
Ext
9260
Email
s.seri@nhs.net
First Name & Middle Initial & Last Name & Degree
Peter R Bill, CSci
Phone
+44 (0)121 333
Ext
9264
Email
peter.bill@nhs.net
First Name & Middle Initial & Last Name & Degree
Bryony Carr, BSc
First Name & Middle Initial & Last Name & Degree
Andrew R Lawley, MD
Facility Name
Aston University
City
Birmingham
State/Province
West Midlands
ZIP/Postal Code
B4 7ET
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sukhvir Wright, MD, PhD
Phone
+44 (0) 121 204
Ext
3953
Email
s.wright5@aston.ac.uk
First Name & Middle Initial & Last Name & Degree
Ana Checa-Ros, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
All data recruited at BCH and at the ABC will be pseudonymized before being shared with the PI at Aston University to protect patient confidentiality.
Citations:
PubMed Identifier
10541598
Citation
Capovilla G, Beccaria F, Romeo A, Veggiotti P, Canger R, Paladin F. Effectiveness of a particular blue lens on photoparoxysmal response in photosensitive epileptic patients. Ital J Neurol Sci. 1999 Jun;20(3):161-6. doi: 10.1007/s100720050026.
Results Reference
background
PubMed Identifier
16529617
Citation
Capovilla G, Gambardella A, Rubboli G, Beccaria F, Montagnini A, Aguglia U, Canevini MP, Casellato S, Granata T, Paladin F, Romeo A, Stranci G, Tinuper P, Veggiotti P, Avanzini G, Tassinari CA. Suppressive efficacy by a commercially available blue lens on PPR in 610 photosensitive epilepsy patients. Epilepsia. 2006 Mar;47(3):529-33. doi: 10.1111/j.1528-1167.2006.00463.x.
Results Reference
background
PubMed Identifier
16146439
Citation
Fisher RS, Harding G, Erba G, Barkley GL, Wilkins A; Epilepsy Foundation of America Working Group. Photic- and pattern-induced seizures: a review for the Epilepsy Foundation of America Working Group. Epilepsia. 2005 Sep;46(9):1426-41. doi: 10.1111/j.1528-1167.2005.31405.x.
Results Reference
background
PubMed Identifier
14706039
Citation
Guerrini R, Genton P. Epileptic syndromes and visually induced seizures. Epilepsia. 2004;45 Suppl 1:14-8. doi: 10.1111/j.0013-9580.2004.451011.x.
Results Reference
background
Citation
Harding, G., & Jeavons, P. (1994). Photosensitive Epilepsy: Clinics in Developmental Medicine. London, UK: McKeith Press.
Results Reference
background
PubMed Identifier
22091642
Citation
Kasteleijn-Nolst Trenite D, Rubboli G, Hirsch E, Martins da Silva A, Seri S, Wilkins A, Parra J, Covanis A, Elia M, Capovilla G, Stephani U, Harding G. Methodology of photic stimulation revisited: updated European algorithm for visual stimulation in the EEG laboratory. Epilepsia. 2012 Jan;53(1):16-24. doi: 10.1111/j.1528-1167.2011.03319.x. Epub 2011 Nov 16.
Results Reference
background
PubMed Identifier
16714268
Citation
Mainster MA. Violet and blue light blocking intraocular lenses: photoprotection versus photoreception. Br J Ophthalmol. 2006 Jun;90(6):784-92. doi: 10.1136/bjo.2005.086553.
Results Reference
background
PubMed Identifier
8529557
Citation
Quirk JA, Fish DR, Smith SJ, Sander JW, Shorvon SD, Allen PJ. Incidence of photosensitive epilepsy: a prospective national study. Electroencephalogr Clin Neurophysiol. 1995 Oct;95(4):260-7. doi: 10.1016/0013-4694(95)00118-i.
Results Reference
background
PubMed Identifier
23891468
Citation
Verrotti A, Grosso S, D'Egidio C, Parisi P, Spalice A, Pavone P, Capovilla G, Agostinelli S. Valproate in adolescents with photosensitive epilepsy with generalized tonic-clonic seizures only. Eur J Paediatr Neurol. 2014 Jan;18(1):13-8. doi: 10.1016/j.ejpn.2013.06.006. Epub 2013 Jul 26.
Results Reference
background
PubMed Identifier
10986003
Citation
Yalcin AD, Kaymaz A, Forta H. Reflex occipital lobe epilepsy. Seizure. 2000 Sep;9(6):436-41. doi: 10.1053/seiz.2000.0424.
Results Reference
background

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Efficacy of Lenses in Abolishing Photoparoxysmal Responses

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