CURATE.AI COR-Tx Trial for Post Brain Radiotherapy Patients

CURATE.AI Optimised Digital COgnitive Rehabilitation Therapy (COR-Tx) for Post Brain Radiotherapy Patients: CURATE.AI COR-Tx Mixed-methods Feasibility Clinical Trial

Cognitive deficit is common in patients who have undergone whole brain or partial brain radiotherapy. To counteract intellectual deterioration, the conventional strategies includes drug- based treatments such as donezepil and memantine, which have shown to only provide marginal improvement and, cognitive training regimens, both of which are usually administered at fixed dose/intensities often leading to sub-optimal responses. This study aims to address this clinically relevant problem by harnessing the CURATE.AI platform to identify N-of-1cognitive training profiles the can enhance learning trajectories through individualised calibration and training regimens. CURATE.AI is a phenotypic personalised medicine (PPM) platform that correlates a patient's phenotypic response (cognitive performance) to a certain input (training intensity) based exclusively on the patient's data. This PPM platform is independent of biological system or interventional agent and can be applied to any disorder treatment where dosing/intensity could be better personalised. CURATE.AI is expected to optimise/personalise cognitive training in post-brain radiotherapy patients by dynamically modulating the intensity of a digital cognitive test battery that measures executive processing, multitasking and perceptual learning tasks. In addition, this clinical feasibility trial aims to assess this cognitive test battery as a potential analogous or complementary diagnostic tool as compared to traditional cognitive evaluations performed by a clinician.

Study Overview

• Status: Recruiting
• Conditions: Cognitive Decline
• Intervention / Treatment: Device: CURATE.AI

Detailed Description

Brain radiotherapy causes downstream cognitive deficits. Drug-based cognitive decline treatments show little improvement and side effects may reduce patient compliance. Regimens are usually administered at a fixed dose that doesn't incorporate high patient variability, leading to sub-optimal responses.

Effective cognitive training can improve cognitive performance. Artificial intelligence platforms show great potential for training personalisation. The CURATE.AI platform can be used to identify N-of-1 (single subject) training profiles that can be used to optimise learning trajectories through individualised calibration and training regimens, potentially leading to improved outcomes compared to standard static or adaptive training strategies. CURATE.AI uses only a subject's own performance data to identify the intensity needed for his/her best output. As the subject evolves during the course of intervention, the training intensities are dynamically modulated to maintain performance within a given range.

Here the investigators propose to test the feasibility of CURATE.AI, with a digital cognitive test battery as the interface, as an adaptive training platform for cognitive training addressed to improve brain cancer radiotherapy patients' cognitive performance. The acceptability, implementation and limited efficacy of the digital intervention (DI) will be explored. In addition, the investigators propose to test the feasibility of the digital cognitive test battery potential as a digital diagnostic (DD) tool as compared to traditional cognitive evaluations performed by a clinician. User experience and usability will also be explored.

• Study Type: Interventional
• Enrollment (Anticipated): 15
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dr Balamurugan A Vellayappan; Phone Number: +65 67795555; Email: bala_vellayappan@nuhs.edu.sg
• Study Contact Backup: Name: Qian Yee, Queenie Chai; Email: queenie_qy_chai@nuhs.edu.sg

Study Locations

• Singapore
  • Singapore, Singapore
    • Recruiting
    • National University Hospital
    • Contact: Qian Yee, Queenie Chai, Coordinator; Email: queenie_qy_chai@nuhs.edu.sg
    • Contact: Fatin Aliyah, Coordinator; Email: fatin_hussin@nuhs.edu.sg
  • Singapore, Singapore
    • Recruiting
    • The N.1 Institute for Health (N.1), NUS
    • Contact: Xavier Tadeo, PhD; Email: biextc@nus.edu.sg
    • Contact: Yoong Hun Ong, MSc; Phone Number: +6596680807; Email: yh.ong@nus.edu.sg
    • Sub-Investigator: Theodore Kee, MSc
    • Sub-Investigator: Alexandria Remus, PhD
    • Sub-Investigator: Chris Asplund, A/Prof

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 99 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age >21 years.
• ECOG performance status 0 to 2.
• Patients with a neoplastic condition (benign or malignant) involving the brain or skull requiring radiotherapy (with or without chemotherapy).
• Patients with a life expectancy of at least 6 months.

Exclusion Criteria:

• Pregnant or breastfeeding women.
• Patients undergoing stereotactic radiosurgery (single fraction).
• Patients who are undergoing re-irradiation to the same area of the brain.
• Patients physically incapable of using computer tablet (either due to vision loss or dominant hand weakness)
• Patients who cannot understand spoken English language.
• Patients who are unable to give informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: CURATE.AI; A cognitive evaluation and a Digital Diagnostic (DD) session performed anytime before radiotherapy will serve as the baseline. After the radiotherapy treatment, which can last between 1 to 6.5 weeks, patients will have a variable recovery time (0 to 4 weeks). Subsequently, patients will be subject to a cognitive evaluation and a DD session, right before starting the Digital Intervention (DI) training. This training will comprise ten weeks of DI (three 10-15 minute sessions per week). Patients will complete cognitive evaluations and DD sessions at the end of DI, and 16 and 32 weeks after the end of DI.

Device: CURATE.AI; CURATE.AI will be utilised to provide personalised training intensity recommendations (low, medium or high) to the patients during the digital cognitive test battery DI session. The difficulty of each task will be modulated by CURATE.AI by adjusting the frequency of critical events that demand evaluation and/or response.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient acceptability of the digital cognitive test battery DI/DD obtained during a semi-structured interview	Qualitative summary of patient acceptability of the digital cognitive test battery DI/DD	One visit 60 minutes (at the end of the 10 week intervention)
Patient adherence to the DI/DD	Percentage of completed DI/DD sessions	up to 12 months
Patient attrition rate to the DI/DD	Percentage of patients that drop out of DI/DD	up to 12 months
Percentage of CURATE.AI profiles successfully created and applied		up to 12 months
Timely delivery of DI/DD at indicated time points	Percentage of DI/DD sessions successfully delivered by study team at indicated time points	up to 12 months
Digital intervention limited efficacy	Change in cognitive performance as measured by the standard of care cognitive evaluations pre-post digital intervention	up to 12 months
Digital diagnostic limited efficacy	Correlation between standard of care cognitive evaluations scores and digital diagnostic scores	up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1. Usability of the digital cognitive test battery DI/DD obtained during a semi-structured interview	Qualitative summary of patient usability of the digital cognitive test battery DI/DD	One visit 60 minutes (at the end of the 10 week intervention)

Collaborators and Investigators

• Sponsor: National University Hospital, Singapore
• Collaborators: National University, Singapore; The N.1 Institute for Health (N.1)
• Investigators: Principal Investigator: Dr Balamurugan A Vellayappan, National University Cancer Institute, Singapore

Publications and helpful links

General Publications

• Kee, Theodore & Weiyan, Chee & Blasiak, Agata & Chong, Jordan & Chen, Jonna & Yeo, B.T. Thomas & Ho, Dean & Asplund, Christopher. (2019). Harnessing CURATE.AI as a Digital Therapeutics Platform by Identifying N-of-1 Learning Trajectory Profiles. Advanced Therapeutics. 2. 1900023. 10.1002/adtp.201900023.
• Zarrinpar A, Lee DK, Silva A, Datta N, Kee T, Eriksen C, Weigle K, Agopian V, Kaldas F, Farmer D, Wang SE, Busuttil R, Ho CM, Ho D. Individualizing liver transplant immunosuppression using a phenotypic personalized medicine platform. Sci Transl Med. 2016 Apr 6;8(333):333ra49. doi: 10.1126/scitranslmed.aac5954.
• Pantuck AJ, Lee DK, Kee T, Wang P, Lakhotia S, Silverman MH, Mathis C, Drakaki A, Belldegrun AS, Ho CM, Ho D. Modulating BET bromodomain inhibitor ZEN-3694 and enzalutamide combination dosing in a metastatic prostate cancer patient using CURATE. AI, an artificial intelligence platform. Advanced Therapeutics. 2018 Oct;1(6):1800104.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 14, 2021
• Primary Completion (ANTICIPATED): January 1, 2022
• Study Completion (ANTICIPATED): July 1, 2022

Study Registration Dates

• First Submitted: March 2, 2021
• First Submitted That Met QC Criteria: April 13, 2021
• First Posted (ACTUAL): April 19, 2021

Study Record Updates

• Last Update Posted (ACTUAL): November 12, 2021
• Last Update Submitted That Met QC Criteria: November 10, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: Radiotherapy; Oncology; Digital therapeutics; Cognitive training; Cognitive evaluation; CURATE.AI; Digital diagnostic; Phenotypic Personalised Medicine (PPM); Multi-Attribute Task Battery (MATB); Training intensity
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction
• Other Study ID Numbers: 2020/00249

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No