PatiEnt Neuropsychological outcomeS After laseR Ablation
Conditions: Cognitive Change
Sponsor: Monteris Medical

CL10147
 PENSAR Study Protocol    
    Rev A 
Monteris Medical 
Strictly Confidential 
Page 1 of 10 
PatiEnt Neuropsychological outcomeS After laseR ablation 
NCT05075850 
July 21, 2021 

CL10147                                  
 PENSAR Study Protocol     
    Rev A 
 
 
Monteris Medical 
Strictly Confidential 
Page 2 of 10 
 
 
 
PROTOCOL SIGNATURE PAGE 
 
 
PatiEnt Neuropsychological outcomeS After laseR ablation  
 
 
I have read this protocol and agree to adhere to the requirements. I will provide copies of this protocol 
and all pertinent information to the study personnel under my supervision and my hospital institutional 
review board (IRB). I will discuss this material with them and ensure the conduct of the study according to 
this protocol, including applicable laws, regulatory requirements, general standards of good clinical 
practice and any other instructions provided by the Sponsor and the IRB. 
 
 
 
 
Site Name 
Site Investigator (Printed Name) 
Site Investigator (Signature) 
Date 

CL10147                                  
 PENSAR Study Protocol     
    Rev A 
 
 
Monteris Medical 
Strictly Confidential 
Page 3 of 10 
 
TABLE OF CONTENTS 
1 
Definitions ........................................................................................................................................ 3 
2 
Background & Purpose .................................................................................................................... 4 
3 
Intervention/treatment ...................................................................................................................... 4 
4 
Study Design Overview .................................................................................................................... 4 
4.1 
Study Objectives ........................................................................................................................ 4 
4.2 
Study Population ....................................................................................................................... 5 
5 
Informed Consent (ICF) ................................................................................................................... 5 
6 
Visit Schedule and Data Collection .................................................................................................. 5 
7 
Study Completion or Withdrawal ...................................................................................................... 8 
8 
Adverse Event Reporting ................................................................................................................. 8 
9 
Protocol Deviations .......................................................................................................................... 8 
10 
Data Analysis ................................................................................................................................... 8 
11 
Study Management And Data Collection ......................................................................................... 8 
12 
Administrative Responsibilities ........................................................................................................ 9 
12.1 
Sponsor Responsibilities ........................................................................................................... 9 
12.2 
Investigator Responsibilities ...................................................................................................... 9 
12.3 
Institutional Review Board (IRB) Approval ................................................................................ 9 
12.4 
Confidentiality ............................................................................................................................ 9 
13 
Monitoring ...................................................................................................................................... 10 
14 
Investigator Reports and Records Requirements .......................................................................... 10 
15 
Use of Information and Publication ................................................................................................ 10 
16 
References ..................................................................................................................................... 10 
 
1 
DEFINITIONS  
Term 
Definition 
Comprehensive 
neuropsychological 
assessment 
Defined by AACN guidance (Board of Directors, 2007):   
“Neuropsychological evaluations vary in content depending on their purpose, 
but they typically assess multiple neurocognitive and emotional functions. 
Primary cognitive domains include: intellectual functions; academic skills (e.g., 
reading, writing, math); receptive and expressive language skills (e.g., verbal 
comprehension, fluency, confrontation naming); simple and complex attention; 
learning and memory (e.g., encoding, recall, recognition); visuospatial abilities; 
executive functions, problem-solving and reasoning abilities; and sensorimotor 
skills. Ideally, assessments should also include measures designed to assess 
personality, social-emotional functioning, and adaptive behavior.” 
Cognitive Domain 
For this study, collected cognitive domains include Language,  
Executive Function, Attention, Verbal Memory, Visual Memory, Verbal 
Fluency, and Motor Function 
Preferred 
neuropsychological 
tests 
For this study, tests include Boston Naming, Trails making Test A and Test B, 
Digit Span, Logical memory test (subtest from Wechsler Memory Scale IV), 
BVMT--Brief Visuospatial Memory Test, Animal Fluency test, and Grooved 
Pegboard 
LAANTERN registry 
ClinicalTrials.gov identifier NCT02392078, Protocol CL10027 
LAANTERN Index 
Procedure 
First NeuroBlate® System procedure after signing the LAANTERN Informed 
Consent Form. 
Protocol Deviation 
An event that did not occur according to the protocol and which will include 
issues with consenting and missed follow-up Neuropsychology testing. 
Visual field testing 
Humphry Automated fields for visual field testing to assess peripheral vision.  
 
 

CL10147                                  
 PENSAR Study Protocol     
    Rev A 
 
 
Monteris Medical 
Strictly Confidential 
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2 
BACKGROUND & PURPOSE  
A portion of patient concern regarding epilepsy surgery is potential for cognitive decline or functional 
deficit following surgery.  To address this concern, comprehensive neuropsychological testing is 
performed as part of the surgical epilepsy evaluation and at follow-up. While neuropsychological and 
functional change after open resection is well described, change following Laser Interstitial Thermal 
Therapy (LITT) is less well known. The goal of this study is to assess and describe differences in post-
surgical neuropsychological test scores in a population of patients with epilepsy who are undergoing 
LITT.  This study will also assess a subset of patients with mesial temporal lobe epilepsy for changes to 
visual fields. This study is being conducted as a sub-study within the LAANTERN registry; therefore, all 
enrolled patients in PENSAR must be consented to both protocols. 
 
3 
INTERVENTION/TREATMENT 
• 
All subjects will undergo comprehensive neuropsychological assessment post-LITT per standard 
of care practice.  
• 
Visual field testing will be conducted in a subset of enrolled patients. 
 
4 
STUDY DESIGN OVERVIEW 
This is a multicenter sub-study that will include comprehensive neuropsychological assessment data 
collection done at baseline (within 1 year prior to the index LITT procedure) and at follow-up (at least 6 
months from the index LITT procedure). Visual field testing will be conducted in a subset of enrolled 
patients. Up to 250 subjects may be enrolled at up to 15 study sites.  
 
 
4.1 STUDY OBJECTIVES 
Primary outcome measure: Site-determined cognitive changes per domain 
[Time Frame: 6+ months] 
Neuropsychological test data will be collected for all study participants to describe 
cognitive domain specific changes as a cohort. Change will be assessed from raw test 
scores and demographically corrected standardized scores (where available).  
 
Secondary outcome measure 1: Change in raw test scores from standard battery of 
preferred neuropsychological tests 
[Time Frame: 6+ months] 
Describe the observed change or stability of neuropsychological test scores in patients 
who underwent laser ablation surgery. Change will be assessed from raw test scores and 
demographically corrected standardized scores (where available).  
 
Secondary outcome measure 2: Incidence of visual field deficits in patients with MTLE. 
[Time Frame: 6+ months] 
Visual field testing using Humphry automated fields (HVF 24-2 SITA standard) will be 
conducted for a subset of patients to identify visual field deficits resulting after the LITT 
procedure.

CL10147                                  
 PENSAR Study Protocol     
    Rev A 
 
 
Monteris Medical 
Strictly Confidential 
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4.2 STUDY POPULATION 
Subjects who meet inclusion criteria and no exclusion criteria and sign the Informed Consent Form (ICF) 
(CL10149) will be considered enrolled in this study. Subjects will continue to be identified by their unique 
identification number (ID) assigned in LAANTERN and will be presented with additional electronic Case 
Report Forms (eCRFs) applicable for the PENSAR study. 
 
Inclusion Criteria: 
1. Patient or legally authorized representative provides written authorization and/or consent. 
2. Patient is enrolled in the LAANTERN trial and had an epilepsy diagnosis without the 
presence of a malignant brain tumor. 
3. Patient is 16 years of age or older. 
4. Patient has completed a baseline comprehensive neuropsychological assessment with a 
neuropsychologist. 
 
Exclusion Criteria: 
1. Patient does not complete the index LITT procedure as specified in the LAANTERN 
registry. 
 
5 
INFORMED CONSENT (ICF) 
The Sponsor will provide a template ICF to each site for Institutional Review Board (IRB) submission prior 
to the site initiation. This template may be modified to suit the requirements of the individual study site. 
The Sponsor must pre-approve all changes to the ICF prior to initial submission to the IRB. A copy of the 
IRB-approved ICF must be sent to the Sponsor and the original copy must be retained at the study site. If 
the ICF is amended by the reviewing IRB, the Sponsor must pre-approve all changes to the ICF prior to 
submission. In addition, a copy of the approved documents must be provided by the Investigator to the 
Sponsor prior to enrollment of subjects in the study.  
The Investigator or assigned designee must administer this approved ICF to each prospective study 
subject and obtain the subject’s signature or a legally authorized representative signature along with the 
date of consent and prior to performing any PENSAR study related activity. The ICF must be obtained in 
accordance with 21 CFR Part 50. Subjects must be informed about their right to withdraw from the study 
at any time and for any reason without sanction, penalty, or loss of benefits to which the subject is 
otherwise entitled and informed that withdrawal from the study will not jeopardize their future medical 
care. A copy of ICF must be given to each subject enrolled in the study. The institutional standard subject 
consent form does not replace the study ICF. 
 
6 
VISIT SCHEDULE AND DATA COLLECTION 
Neuropsychological testing is typically conducted as standard of care at baseline and at follow-up. The 
testing should be conducted by qualified neuropsychologist. The neuropsychologist should use the same 
tests at follow-up so that the status of change from baseline may be assessed.  
Collection of preferred test results will allow for pooling of multicenter data for the Primary Outcome and 
Secondary Outcome 1. A listing of preferred and commonly used tests assessing multiple 
neuropsychological functions are provided in Table 1.  
Additional neuropsychological tests consisting of each site’s standard-of-care battery (along with raw 
scores and demographically corrected standardized scores) will also be accepted in cases where 
preferred test results are not available. 
Visual fields testing will be conducted as the study intervention/treatment at follow-up using Humphry 
automated fields (HVF 24-2 SITA standard) for visual field testing to assess peripheral vision after at least 
6 months from the index LITT procedure in cases where:  
• 
The patient is diagnosed with mesial temporal lobe epilepsy (MTLE)/mesial temporal sclerosis 
(MTS).  
• 
The patient has an amygdala/hippocampal LITT ablation.  

CL10147                                  
 PENSAR Study Protocol     
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Monteris Medical 
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• 
The patient is surgically naïve prior to the LITT procedure (excluding surgical placement of 
diagnostic electrodes). 
• 
The patient does not have glaucoma or other known retina/eye issues that would interfere with 
Visual field testing or interpretation of the results. 
Single field Analysis result from both eyes and summary data of normal/abnormal findings will be 
collected. 
 
 
 
Informed Consent/Baseline Visit 
(Must be after LAANTERN consent is obtained) 
 Obtain Informed 
Consent in PENSAR. 
 Collect baseline 
Neuropsychology 
assessment. 
Follow-up Visit 
 
 
 
Follow LAANTERN study flow. After at least 6-
months from index LITT procedure, move to 
follow-up visit for PENSAR. 
Figure 1: Study Flow Chart 
Conclude PENSAR data collection and Continue 
LAANTERN Study Visit schedule 
 Collect follow-up 
Neuropsychology 
assessment  
 Collect Visual field-testing result 
(HVF 24-2 SITA standard) 
Only if subject is eligible for cohort 

CL10147                                  
 PENSAR Study Protocol     
    Rev A 
 
 
Monteris Medical 
Strictly Confidential 
Page 7 of 10 
 
 
Table 1: Comprehensive Neuropsychological Testing 
Preferred Neuropsychological tests  
(Secondary outcome measure 1) 
Cognitive domain  
(Primary outcome measure and Secondary 
outcome measure 1) 
1. Boston Naming 
Language 
2. Trails making Test A and Test B  
Executive Function* 
3. Digit Span 
Attention* 
4. Logical memory test  
(subtest from Wechsler Memory Scale IV) 
Verbal Memory 
5. BVMT--Brief Visuospatial Memory Test 
Visual Memory 
6. Animal Fluency test 
Verbal Fluency 
7. Grooved Pegboard 
Motor Function 
*Components of Verbal Memory  
Table 2: Study Visit Schedule* 
 
Baseline 
(within 1 year prior to the index 
LITT procedure) 
Follow-up  
(At least 6 months from the 
index LITT procedure) 
Inclusion/Exclusion Assessment 
X 
- 
Comprehensive neuropsychological 
testing (See Table 1) 
 
Collection of preferred test scores: 
• 
Boston Naming 
• 
Trails making Test A and Test B  
• 
Digit Span 
• 
Logical memory test (subtest from 
Wechsler Memory Scale IV) 
• 
BVMT--Brief Visuospatial Memory 
Test 
• 
Animal Fluency test 
• 
Grooved Pegboard 
 
If applicable, collection of change in 
substituted (non-preferred)§ test scores 
X† 
 
 
 
X 
X 
X 
X 
 
X 
X 
X 
 
 
- 
X‡ 
 
 
 
X 
X 
X 
X 
 
X 
X 
X 
 
 
X 
Visual field testing|| 
- 
X 
End of Study 
Patient participation in the study will end after applicable follow-
up testing is completed or upon subject withdrawal. 
*The visit schedule is calculated from the date of the LITT procedure captured under the LAANTERN protocol.  
†Baseline testing is conducted as standard of care and is required to meet inclusion criterion 4.  
‡If applicable, any patient-reported subjective memory changes are collected. 
§If the preferred neuropsychological tests were not assessed at baseline, other comparable tests may be substituted; 
however, only the change in score will be collected at follow-up. 
||Visual fields will be assessed and collected only in cases where:  
• 
The patient is diagnosed with mesial temporal lobe epilepsy (MTLE)/mesial temporal sclerosis (MTS).  
• 
The patient has an amygdala/hippocampal LITT ablation.  
• 
The patient is surgically naïve prior to the LITT procedure (excluding surgical placement of diagnostic 
electrodes). 
• 
The patient does not have glaucoma or other known retina/eye issues that would interfere with Visual field 
testing or interpretation of the results.  

CL10147                                  
 PENSAR Study Protocol     
    Rev A 
 
 
Monteris Medical 
Strictly Confidential 
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7 
STUDY COMPLETION OR WITHDRAWAL 
Subjects will complete the PENSAR study once follow-up comprehensive neuropsychological testing is 
completed and/or their participation in the LAANTERN registry ends. 
 
8 
ADVERSE EVENT REPORTING 
No separate adverse events will be collected or reported for this study. Adverse events will continue to be 
collected and reported under the LAANTERN protocol criteria and definitions. Visual field test results and 
neuropsychological outcomes are not reportable adverse events unless they meet LAANTERN protocol 
criteria and definitions.  
 
9 
PROTOCOL DEVIATIONS 
Anticipated protocol deviations include improper consenting of subject (i.e., consent not obtained and 
improper consenting) and not completing follow-up neuropsychological testing. All deviations will be 
reported to Monteris Medical. It is the site’s responsibility to report deviations in compliance with their 
Institutional Review Board if required. 
 
10 DATA ANALYSIS 
Study objectives will not be statistically powered given the anticipated heterogeneity in available 
neuropsychological test results.  
Scores will be collected to assess domain specific changes for the Primary outcome measure using pre-
defined clinically meaningful cut scores (based on previously described methods1,2):  
• 
Changes of 1.5 standard deviations will be considered improved (+) or worsened (-). 
• 
Changes of 2.5 standard deviations will be considered substantial post-operative improvements 
(+) or worsening (-).  
• 
Any score change less than 1.5 standard deviation will be considered unchanged and the result 
of anticipated variability.  
 
Descriptive statistics will be used to summarize the results for Secondary Outcome measures: 
• 
Continuous variables: The total count, mean, standard deviation, minimum, and maximum will be 
provided. 
• 
Categorical variables: Total count and percentage will be provided. 
 
Ad hoc, exploratory analyses may be conducted if sufficient sample size allows for correlation or 
multivariate assessment of patient subsets (e.g., those with improvement or worsening). 
 
11 DATA COLLECTION AND MANAGEMENT  
The study will be performed in accordance with all requirements set forth in the U.S. regulations, 21 Code 
of Federal Regulations (CFR) Parts 50 (Protection of Human Patients), 56 (Institutional Review Board), 
and applicable requirements from the reviewing IRB for the study at each site.  
 
The study data will be hosted in the same electric data capture (EDC) system as the LAANTERN registry 
where it will continue to follow compliance with the U.S. regulations, 21 CFR part 11, Electronic Records; 
Electronic Signatures.  
 
All required data for this study will be collected on standardized Case Report Forms (CRFs). 
Qualified study staff at each investigational site will perform primary data collection drawn from source 
document (e.g., hospital chart) review. All CRFs will be subject to review for omitted data, gross data 
inconsistencies, illegible data, and deviations. Any deficiencies or deviations will be reviewed, and any 
necessary action determined (e.g., data query, communication to the study center).  
De-identified source documents will be collected for neuropsychological testing results at baseline and 
follow-up. De-identified source for the Single Field Analysis (HVF24-2 printouts) from both eyes will be 
collected as well as summary data of normal/abnormal findings.  

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Data review (including crosschecks) will be performed, and any discovered errors will be reported to the 
study site using the data correction and query process (as necessary). The study site will review the 
query, respond, and make any necessary corrections or comments. The data cleaning cycle will be 
repeated until all data are considered clean.  
 
12 ADMINISTRATIVE RESPONSIBILITIES  
12.1 SPONSOR RESPONSIBILITIES 
The Sponsor’s responsibilities for this study are to: 
• 
Select qualified clinical investigators and study sites 
• 
Provide study protocol training to participating study sites including the Investigator and staff 
conducting the study 
• 
Provide financial support to each study site which is fair, reasonable, and equitable to fair market 
value 
• 
Follow/promote all applicable regulatory standards per CFRs at each study site  
• 
Own and control the use of the data, including review and approval of study-related 
publications/presentations, etc.  
 
12.2 INVESTIGATOR RESPONSIBILITIES 
The Primary Investigator for each site is responsible for ensuring the study is conducted according to: 
• 
All signed agreements (including financial disclosures) 
• 
The Study Protocol 
• 
IRB guidelines 
• 
Applicable Food and Drug Administration (FDA) regulations 
 
The Investigator for each site may not begin enrollment until Sponsor receives and approves (when 
necessary) required documents, including a completed and signed Investigator Agreement/Clinical Trial 
Agreement (or equivalent), Protocol Signature Page, IRB and ICF approvals.  
It is acceptable for the Investigator to delegate one or more of the above functions to an associate or Sub-
Investigator or trained Study Coordinator; however, the Investigator remains responsible for the proper 
conduct of the clinical investigation, including obtaining and documenting proper study informed consent, 
collecting all required data, submitting accurate and complete CRFs, etc. 
At each site, appropriate procedures must be followed to maintain subject confidentiality according to 
appropriate local regulations (e.g., Health Insurance Portability and Accountability Act in the U.S.). Each 
site may have its own internal procedures or requirements for use and release of subject medical 
information in research studies. Each Investigator is responsible for obtaining appropriate approvals, 
consents, or releases of medical information as dictated by their relevant patient privacy laws. 
The study is not transferable to other sites attended by the Investigator unless prior approval is obtained 
from the appropriate IRB and the Sponsor.  
 
12.3 INSTITUTIONAL REVIEW BOARD (IRB) APPROVAL 
Investigators must submit the study protocol and ICF to their reviewing IRB and obtain IRB written 
approval before being allowed to conduct and participate in the study. Each Investigator must submit to 
the Sponsor a copy of the IRB approval letter, specific to this protocol and addressed to Investigator, 
certifying study approval prior to enrolling subjects into the study. This approval letter should identify the 
study name, study protocol number (including revision number), the date of the approval as well as the 
expiration date of such an approval. The Investigator is also responsible for fulfilling any conditions of 
approval imposed by the IRB, and for maintaining continuation of the approval during the entire study 
period. The Investigator must provide the Sponsor with copies of such approvals.  
 
12.4 CONFIDENTIALITY 
All information and data sent to the Sponsor concerning subjects or their participation in this study will be 
considered confidential. All data used in the analysis and reporting of this evaluation will be used in a 
manner without identifiable reference to the subject.  
 

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13 MONITORING  
The Sponsor or a Sponsor representative will monitor the progress of the study as described in the Study 
Monitoring Plan. The Investigator consents to visits by the staff of the Sponsor or its representatives to 
review the study subject medical records, including any test or laboratory data that might have been 
recorded on diagnostic test media (e.g., MRI). The Sponsor will request that any source documents to be 
submitted to the sponsor, sponsor representative be de-identified (subject’s name and other personal 
identifiers must be removed and replaced with the study subject ID).  
 
14 INVESTIGATOR REPORTS AND RECORDS REQUIREMENTS  
The Investigator is responsible for the completion and submission to the Sponsor of all CRFs and 
deviations from the protocol. If any action is taken by an IRB with respect to the study, the information 
must be forwarded to the Sponsor in a timely manner. All data must be stored and retained by the 
investigative site for a minimum of 2 years following a notification from Sponsor that all investigative sites 
are complete, terminated, or discontinued. Should the investigator withdraw from the responsibility of 
retaining study records, then custody of the records transfers to a person assuming responsibility. 
Sponsor will be notified in writing of new custodian by the investigative site. 
 
15 USE OF INFORMATION AND PUBLICATION 
Publications will follow guidelines in the LAANTERN Registry and the associated Publication Plan 
(CL10084). A committee will be formed for prioritization of PENSAR-specific publications. This study will 
be submitted for inclusion in the clinical trial study at: http://www.ClinicalTrials.gov.  
 
16 REFERENCES 
1.  Bermudez CI, Jermakowicz WJ, Kolcun JPG, et al. Cognitive outcomes following laser interstitial 
therapy for mesiotemporal epilepsies. Neurology: Clinical Practice. Published online September 6, 
2019:10.1212/CPJ.0000000000000728. doi:10.1212/CPJ.0000000000000728 
2. 
Board of Directors. (2007). American Academy of Clinical Neuropsychology (AACN) Practice 
Guidelines for Neuropsychological Assessment and Consultation. The Clinical Neuropsychologist, 
21(2), 209–231. https://doi.org/10.1080/13825580601025932 
 
3.  Drane DL, Loring DW, Voets NL, et al. Better object recognition and naming outcome with MRI-
guided stereotactic laser amygdalohippocampotomy for temporal lobe epilepsy. Epilepsia. 
2015;56(1):101-113. doi:10.1111/epi.12860