INTERAGENCY SERVICE AGREEMENT (ISA)

AMENDMENT

ARIZONA DEPARTMENT OF

HEALTH SERVICES

OFFICE OF PROCUREMENT

150 N 18th Ave., Ste. #530 Phoenix, Arizona 85007

AGREEMENT NO.: CTR065451 AMENDMENT NO.: 02 Procurement Officer:

Brittany Manuel

Revised 04/08/2024

CPAE Registry & Biospecimen Repository

Effective upon signature by both parties it is mutually agreed that the ISA is amended as follows:

1. Pursuant to the Uniform Terms and Conditions, Provision Twenty-Six (26), Miscellaneous, Section 26.3 the Agreement is hereby revised with the following:

1.1 The Scope of Work is revised and replaced.

1.2 The Price Sheet is revised and replaced.

ALL CHANGES ARE REFLECTED IN RED

ALL OTHER PROVISIONS SHALL REMAIN IN THEIR ENTIRETY

Contractor hereby acknowledges receipt and acceptance of above amendment and that a signed copy must be filed with the Procurement Office before the effective date

The above referenced Contract Amendment is hereby executed this _____ day of __________ 20______ at Phoenix, Arizona

(To be filled out by ADHS Procurement Office)

Contractor Signature

Contractor Signature Date

Authorized Signatory’s Name and Title

AZ Board of Regents, University of Arizona Contractor’s Name Procurement Officer Signature

10/23/2025

23 October 25

ARIZONA DEPARTMENT OF

HEALTH SERVICES

OFFICE OF PROCUREMENT

150 N 18th Ave., Ste. #530 Phoenix, Arizona 85007

AGREEMENT NO.: CTR065451 AMENDMENT NO.: 02 Procurement Officer:

Brittany Manuel

Revised 04/08/2024

1. Background

1.1. The Arizona Biomedical Research Centre (ABRC) receives funding from the Arizona Tobacco Tax Fund in accordance with Arizona Revised Statutes §36-275 (https://www.azleg.gov/ars/36/00275.htm)§36-773 (https://www.azleg.gov/ars/36/00773.htm), to engage with various institutions to conduct biomedical research. The University of Arizona (U of A) is conducting research regarding Childhood Postinfectious Autoimmune Encephalopathy (CPAE) disease. They have learned that CPAE produces ongoing brain injury in children due to persistent inflammation from an untreated infection, with severe developmental consequences. Children with these disorders present with acute-onset psychiatric symptoms. CPAE includes disorders such as Pediatric Acute-onset Neuropsychiatric Syndrome (PANS), Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection (PANDAS), and Sydenham chorea.

1.2. Arizona is leading the nation in CPAE research discovery and clinical services. The goal of this Agreement is to expand investigation and knowledge regarding this condition.

Research over the past several decades has greatly increased medical knowledge of CPAE, and clinical leadership by the U of A CPAE Center and its partners across the country have contributed to the understanding of treatment needs and methods. However, there are still unanswered questions regarding the mechanisms that trigger these disorders, methods of prevention, and most effective treatments. There is a critical need for research to clarify the etiology, individual risk, time course and treatment strategies that can respond to core questions regarding this condition.

1.3. A concerted two-pronged approach is expected to reduce pediatric risk related to CPAE in Arizona and will contribute substantially to efforts in the state, nationally and globally to reduce the detrimental impact on children’s lives. This approach includes development of a CPAE patient registry previously initiated with ABRC support to provide researchers in Arizona and national colleagues with expanded accessibility of comprehensive clinical data for diagnostic assessment, evaluating varied interventions and measuring treatment success. Secondly, it includes the establishment of a biorepository linked to the patient registry to promote basic science and translational research aimed at discovering the biological causes, diagnostic and outcome markers, and potential cures for these conditions.

1.4. This work will contribute to knowledge in the field regarding factors that cause/predict CPAE as well as treatment response and effectiveness. Over five (5) years, this will advance Arizona as a national leader in basic science and clinical relational research, providing endless research and collaborative opportunities.

1.5 Childhood Postinfectious Autoimmune Encephalopathy (CPAE) encompasses Pediatric Acute- onset Neuropsychiatric Syndrome (PANS) and Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infections (PANDAS). These conditions are characterized by a sudden onset of obsessive-compulsive disorder (OCD) or severe food restriction (ARFID) along with symptoms of anxiety, emotional lability, depression, aggression, developmental regressions, school performance deterioration, tics, or somatic issues. While behavior therapy is suggested to reduce challenging behaviors and improve treatment adherence, the efficacy of such interventions for CPAE remains understudied. The primary objectives of this project are to evaluate the efficacy of

ARIZONA DEPARTMENT OF

HEALTH SERVICES

OFFICE OF PROCUREMENT

150 N 18th Ave., Ste. #530 Phoenix, Arizona 85007

AGREEMENT NO.: CTR065451 AMENDMENT NO.: 02 Procurement Officer:

Brittany Manuel

Revised 04/08/2024 behavioral treatments for families affected by CPAE and disseminate findings to professionals to improve care systems for children with CPAE.

1.6 Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS) are characterized by abrupt, severe neuropsychiatric symptoms, including obsessive-compulsive behaviors, tics, and food restrictions. Despite their impact, there are no reliable diagnostic tools or biomarkers to monitor disease activity or treatment response. Arizona, through the University of Arizona CPAE Center, is a national leader in research and clinical care for these disorders, having established a comprehensive patient registry and biorepository with ABRC support. All new salivary samples and associated clinical/molecular data will be collected, processed, and stored within the existing University of Arizona Health Sciences Biorepository, following established protocols and harmonized with current biospecimen and clinical datasets. This integration enables multi-modal, longitudinal research and maximizes the value of all biospecimens for collaborative discovery. This project will pioneer non-invasive salivary diagnostics for PANS/PANDAS, enabling earlier detection and improved monitoring of disease activity. By fully integrating with the ongoing CPAE biorepository and registry, the study will provide a robust platform for multi-modal, longitudinal research, accelerate biomarker discovery, and support the development of point-of-care diagnostic tools—directly benefiting Arizona’s pediatric population and advancing national research efforts.

2. Objective

Major Aims of the Project

2.1. AIM 1: Develop the CPAE Patient Registry

2.1.1. Objective 1.1: Enhance services to those with CPAE by maintaining the currently-established research registry and continuing to expand the study cohort;

2.1.2. Objective 1.2: Use the web-based application for data collection, surveys, and databases, Research Electronic Data Capture (REDCap), to refine data collection instruments utilized to collect and maintain the CPAE Registry; and

2.1.3. Objective 1.3: Expand the use of the registry to accelerate CPAE research both internally and through collaboration with other researchers.

2.2. AIM 2: Establish a Biorepository to Promote Basic Science and Translational Research

2.2.1. Objective 2.1: Design an Arizona CPAE biorepository that will integrate with the existing repositories of national collaborators;

2.2.2. Objective 2.2: Collect and catalog biospecimens from pediatric patients seen at the U of A CPAE Clinic; and

2.2.3. Objective 2.3: Manage an Arizona CPAE Biorepository that can provide access to researchers with specimens from children with CPAE from varied time points

ARIZONA DEPARTMENT OF

HEALTH SERVICES

OFFICE OF PROCUREMENT

150 N 18th Ave., Ste. #530 Phoenix, Arizona 85007

AGREEMENT NO.: CTR065451 AMENDMENT NO.: 02 Procurement Officer:

Brittany Manuel

Revised 04/08/2024 of the disease.

2.3. Aim 3: Explore and analyze the effectiveness of direct behavioral interventions through weekly treatment sessions with participants from the CPAE clinic.

2.4. Aim 4: Evaluate the relation of caregiver stress to treatment outcomes and acceptability of treatment procedures.

2.5. Aim 5: Provide education and training to health care providers, psychologists, and other mental health professionals in Arizona to increase awareness of effective behavioral intervention

2.6 Aim 6: Integrated Expansion of the CPAE Biorepository: Identification of Salivary Biomarkers and Oral Microbiome Profiling

2.6.1. Objective 3.1: Identify and validate salivary protein biomarkers for diagnosing and monitoring PANS/PANDAS.

2.6.2. Objective 3.2: Characterize oral microbiome signatures associated with disease onset, progression, and treatment response.

2.6.3. Objective 3.3: Integrate salivary biomarker and microbiome data with the CPAE registry and biorepository to enable comprehensive, longitudinal, and collaborative research.

3. Patient Registry

The patient registry will provide a powerful tool that facilitates observing the course of disease, understanding variations in treatment and outcomes, and examining factors that influence prognosis and quality of life. Over the project period, researchers will focus on maintaining, refining, and expanding data collection and use of the CPAE patient research registry. This registry is a repository of collected medical and clinical data, securely housed within a secure web application for building and managing online surveys and databases commonly referred to as REDCap to analyze and determine the natural course of CPAE symptoms using validated tests of cognitive function, anxiety, neurologic signs, and overall disease severity. During this project period, U of A will be transitioning the existing database to REDCap so that it will become a secure, searchable entity containing data that can be accessed by teams of researchers in Arizona and from other institutions and can be linked to a biorepository of specimens from children with PANS/ PANDAS, normal controls, and non-neurotypical controls. REDCap’s ease-of-use and accessibility offers a convenient method of sharing data collaboratively. U of A will aim to foster and maintain professional collaborations that expand awareness, accelerate promising research, and improve the health of patients with CPAE.

4. Biorepository

4.1. The Biorepository to Promote Basic Science and Translational Research will work in conjunction with partner institutions locally and nationally. Arizona will contribute to efforts to assemble a large dataset across institutions to fuel collaborative research. Over the course of this project, a biorepository will be established at the U of A that will collect and store samples of blood, feces, and other biologic specimens. Patients currently enrolled in

ARIZONA DEPARTMENT OF

HEALTH SERVICES

OFFICE OF PROCUREMENT

150 N 18th Ave., Ste. #530 Phoenix, Arizona 85007

AGREEMENT NO.: CTR065451 AMENDMENT NO.: 02 Procurement Officer:

Brittany Manuel

Revised 04/08/2024 the research registry will be invited to participate in sample collection; for those who consent, efforts will be made to obtain specimens longitudinally, at various points in their disease progression (initial onset, flare, recovery).5.1

4.2. Samples will be collected by the U of A Clinical and Translational Sciences Research Center (CATS), and stored and maintained by the existing University of Arizona Health Sciences Biorepository (UAHS Biorepository), allowing users to set aside samples for their own use, while making samples available to investigators both inside and outside of the university. Initially the project will be focused on collecting samples from children seen at the U of A CPAE Clinic with a confirmed diagnosis. Over the course of the project, the possibility of expanding the scope to include a cohort of neurotypical controls will be explored. The biorepository will serve as an essential component in streamlining ongoing research of PANS and PANDAS at the CPAE Center of Excellence, while also contributing to the forward progress of other researchers.

5. Data Analysis

5.1. This project will employ a data analyst whose primary responsibility will be to abstract information from patient clinical records to ensure accurate and uniform data entry into the REDCap database. Data also will be collected in the registry from direct family input into demographic variables. Clinical variables will be abstracted from the patient clinical record.

Information submitted to the UA Biological Specimen Repository will be managed with strict guidelines for sample preparation and management.

5.2. Data Collection: Data will be gathered about behavioral challenges through rating scales and caregiver report (using the following scales: Parenting Stress Index, Caregiver Burden Inventory, Family Accommodation Scale – Parent Report, Child Behavior Checklist) at baseline and at the end of treatment to assess changes in child challenging behavior and levels of caregiver stress. Additionally, direct observation of behavior via a functional analysis will be conducted at baseline to directly evaluate the conditions under which the child engages in challenging behavior. Based on the results of the functional analysis, behavioral interventions will be individualized to each child and will include therapies based in the science of behavior analysis, including Functional Communication Training and Parent Management Training.

Families will receive coaching by a qualified behavior specialist on their individualized behavioral intervention during weekly 60-minute sessions. Weekly treatment sessions will continue until challenging behavior is reduced by at least 80% (compared to baseline), which may take between 8-20 sessions. The data collected will provide insights into the effectiveness of behavioral interventions for this population.

5.3. Biomarker Data Collection: Participants include 120 patients (including controls) from the University of Arizona’s PANS/PANDAS clinic, enrolled through the ongoing CPAE registry and biorepository. Enrollment will be expanded to include research subjects from Dartmouth to include a more geographically diverse population in the study. Saliva samples will be collected at diagnosis, during exacerbations, and during remission, in parallel with other biospecimens already banked in the biorepository, with all samples processed and stored using the same protocols. All clinical phenotypes, treatment data, and symptom severity scores will be linked in the secure REDCap database and harmonized across all biospecimen types. The key methods involve high-throughput mass spectrometry to identify candidate salivary protein biomarkers, validated via ELISA or Luminex assays, and 16S rRNA sequencing along with

ARIZONA DEPARTMENT OF

HEALTH SERVICES

OFFICE OF PROCUREMENT

150 N 18th Ave., Ste. #530 Phoenix, Arizona 85007

AGREEMENT NO.: CTR065451 AMENDMENT NO.: 02 Procurement Officer:

Brittany Manuel

Revised 04/08/2024 metagenomics to characterize oral microbiome signatures and functional pathways. Statistical modeling will be used to link salivary biomarkers and microbiome features to clinical outcomes, leveraging the unified CPAE database.

5.4. Professional Education: To ensure that practitioners in Arizona are well-informed about the latest behavioral treatments for CPAE, we are seeking support to provide accessible education to providers throughout the state with the goal to increase awareness of effective, empirically supported behavioral interventions for children with CPAE. Two additional training workshops will be provided each year, with the emphasis on empirically supported behavioral interventions. The workshops will be provided to local groups including the Arizona Psychological Association, Arizona Association of Behavior Analysts, and Banner Children’s Virtual Lunch Lecture series. We will reach additional frontline providers including behavior analysts, psychologists, behavioral and mental health practitioners, school counselors, and psychiatrists. We will incorporate this information about behavioral interventions into the existing Arizona CPAE Research Brief disseminated by email to healthcare professionals.

5.5. Regional Conferences: Presentations will be delivered in-person or virtually at two regional conferences a year, which provides a platform for the researchers to share their work and collaborate with other researchers in the field. Additionally, we expect to publish our presented results in scientific, peer-reviewed journals, which allows for external peer-review from outside experts.

6. Tasks

The University shall:

6.1. Objective 1 – Enroll Participants, hire research technician and audit data:

6.1.1. Enroll consenting subjects to participate in the CPAE registry that allows for the longitudinal assessment of CPAE symptoms.

6.1.2. Hire and train a research technician to abstract medical and clinical data relating to CPAE symptoms from consented subjects.

6.1.3. Audit collected data to ensure database integrity, consistency and regulatory compliance.

6.2. Objective 2 – Effective use REDCap to collect and analyze data.

6.2.1. Design and improve REDCap collection tools to maximize data collection efficiency and efficacy.

6.2.2. Train investigators to expand the effective use of REDCap as a survey tool and data collection instrument.

ARIZONA DEPARTMENT OF

HEALTH SERVICES

OFFICE OF PROCUREMENT

150 N 18th Ave., Ste. #530 Phoenix, Arizona 85007

AGREEMENT NO.: CTR065451 AMENDMENT NO.: 02 Procurement Officer:

Brittany Manuel

Revised 04/08/2024

6.2.3. Extract and analyze the REDCap data to explore key research questions.

6.3. Objective 3 – Harmonize the database structure to facilitate research and analyze treatment response elements;

6.3.1. Harmonize database structure and information to facilitate joint research opportunities across CPAE sites interested in collaborative inquiry, and

6.3.2. Utilize collected data to determine elements associated with response to specific treatments that impact CPAE.

6.4. Objective 4 – Support Professional Education and Dissemination;

6.4.1. Conduct two (2) annual training workshops for Arizona providers, psychologists, and mental health professionals, focusing on salivary diagnostics and oral microbiome interpretation in PANS/PANDAS2,

6.4.2. Prepare presentations at two regional conferences per year; publication of results in peer-reviewed journals, and

6.4.2. Integrate findings into the Arizona CPAE Research Brief, disseminated to healthcare professionals statewide,

6.5. Objective 5 – Integration of Salivary Biomarkers and Oral Microbiome Profiling with CPAE Biorepository;

6.5.1. Process and store all saliva samples using the University of Arizona Health Sciences Biorepository protocols, ensuring consistency and quality,.

6.5.2. Data Harmonization - Salivary biomarkers and microbiome data will be linked to the CPAE registry in REDCap, ensuring comprehensive, searchable, and accessible datasets for future research and collaboration,

6.5.2. Collaborative Access - Saliva samples and associated data will be available for approved collaborative projects, maximizing the impact of the resource,

7. Requirements

The University shall provide:

7.1. A fully functioning CPAE Patient Registry by the end of the Contract; and

7.2. A fully operational CPAE Biorepository by the end of the Contract.

8. Deliverables

The University shall provide:

8.1. Quarterly Program Progress Reports on a form provided by the ABRC;

ARIZONA DEPARTMENT OF

HEALTH SERVICES

OFFICE OF PROCUREMENT

150 N 18th Ave., Ste. #530 Phoenix, Arizona 85007

AGREEMENT NO.: CTR065451 AMENDMENT NO.: 02 Procurement Officer:

Brittany Manuel

Revised 04/08/2024

8.1.1. These reports are due not later than thirty (30) days after the end of each calendar quarter with the exception of the quarter ending December 31, which shall be due on February 28.

8.1.2. Reimbursement for expenses will not be approved until the corresponding Program Progress Report is received.

8.2. Quarterly Contractor Expenditure Report (CER)

8.2.1. These reports are due no later than thirty (30) days after the end of each calendar quarter with the exception of the quarter ending December 31, which shall be due on February 28, and

8.2.2. Reimbursement for expenses in these CERs will not be approved until the corresponding Program Progress Report is received.

9. Notices, Correspondence, Reports, and Invoices

9.1. Notices, correspondence, reports, and Contractor Expenditure Reports from the University to ADHS shall be sent to: Biomedical@azdhs.gov.

John S. Garcia, Program Director Arizona Biomedical Research Centre 250 North 17th Avenue Phoenix, AZ 85007 Phone: (602) 364-0157 Email: Biomedical@azdhs.gov

9.2. Notices, Correspondence, Reports, and Payments from ADHS to the University shall be sent to Administration:

The University of Arizona Sponsored Projects & Contracting Services P. O. Box 41867 Tucson, AZ 85717-1867 Email: sponsor@arizona.edu Program:

University of Arizona Sydney Rice, M.D, MSc University of Arizona College of Medicine Tucson – Pediatrics

(520) 626-6301 srice@peds.arizona.edu

9.3. Payments from ADHS to the University shall be sent to the “Remit To” address listed in the University’s Arizona Procurement Portal (APP) profile

ARIZONA DEPARTMENT OF

HEALTH SERVICES

OFFICE OF PROCUREMENT

150 N 18th Ave., Ste. #530 Phoenix, Arizona 85007

AGREEMENT NO.: CTR065451 AMENDMENT NO.: 02 Procurement Officer:

Brittany Manuel

Revised 04/08/2024

Price sheet

Description Year One Year

Two

Year

Three

Year

Four

Year

Five

TOTAL

Personnel and

Benefits

$160,945.00 $190,713.00 $356,713.00 $362,292.00 $264,746.00 $1,335,409.00

Professional &

Outside Services

$61,328.00 $38,378.00 $38,378.00 $37,345.00 $37,345.00 $212,774.00

Other Expenses $5,000.00 $12,000.00 $23,100.00 $23,100.00 $16,100.00 $79,300.00

Indirect Costs -

Capped at 10%

$22,727.00 $23,909.00 $41,809.00 $42,263.00 $31,809.00 $162,517.00

Contract Total $250,000.00 $265,000.00 $460,000.00 $465,000.00 $350,000.00 $1,790,000.00