Clinical trial NCT04972019: Telerehabilitation Cognitive Impairments Following Chemotherapy Feasibility Study
Official title: Home-based Virtual Reality System for the Treatment of Chemotherapy-related Cognitive Impairments - Feasibility Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Cognitive Impairment, Mild
Keywords: chemotherapy
cognitive impairments
breast cancer
executive functions
Lead sponsor: Bright Cloud International Corp
Sponsor class: INDUSTRY
Collaborators: name: National Cancer Institute (NCI)
name: Rutgers, The State University of New Jersey
First posted: 2021-07-22
Enrollment: 40
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Feasibility Sham comparison study:

Participants are randomized equally into the experimental group and a sham control group. Randomization will be based on a randomization table prepared by a contracted bio-statistician.
Primary purpose: TREATMENT

Brief summary: Develop a game-based upper-extremity motor and cognitive rehabilitation system using custom and adaptable virtual reality simulations on a wearable device enhanced with biosensors.

Participants are stage II and stage III breast cancer survivors with lasting cognitive impairments following their first round of chemotherapy. They will be randomized 1:1 into an experimental group and a sham control group. Each group will train in the home for 8 weeks, during which they will perform up to 4 rehabilitation sessions/week (based on tolerance). Each session will start with vitals being measured and logged. Each group will have three clinical evaluations: 1) at baseline; 2) at 8 weeks post-baseline; and 3) at 16 weeks from baseline for follow up.

Experimental group sessions will consist of increasingly more difficult cognitive training tasks in the form of simulated tasks. Biosensors will be sampled while participants interact with these games while wearing the computer system.

Sham control group will have the same number, suration and frequency of sessions, however they will play web games while wearing some the same biosensors.

Caregivers of all subjects will receive a laptop to be used in filling subjective evaluation forms and sending messages to research team. Training will be in the home, so caregivers will need to support the trials by ensuring compliance with the protocol.

All subjects will undergo standardized clinical evaluations at baseline, at 8 weeks and at 16 weeks from baseline. The subjects in the experimental group will have computerized measures taken during each session, and will fill subjective evaluation forms every 4 weeks of active training.

Detailed description: This portion of the study is intended to provide information pertaining to the feasibility of the experimental system for remote integrative (cognitive and motor) therapy of breast cancer survivors (Stage II or III) with lasting cognitive impairments subsequent to their first chemotherapy regimen, and living in the community with a caregiver.

We aim primarily at determining any clinical benefits in improved cognition (primarily in the executive functions domain), but also increased independence in ADLs, and improved mood (reduced depression). Another outcome is the degree of technology acceptance by the targeted population. Training will be done in the home, thus co-dwelling caregivers will also be recruited.

Specific aims are:

1. testing of a wearable device modified with added biosensors, by breast cancer survivors with CRCI.
2. new technology acceptance and ease of use at home by these individuals;
3. clinical benefit to improved cognition (primarily executive functions and cognitive endurance) when experimental therapy is added to daily routine vs. daily routine plus web-based cognitive games;
4. a therapist console module and enhanced automatic session report that will allow remote monitoring of patient exercising and offline data processing and review.

Participants will be randomized equally in an experimental group, or a sham control group. Experimental subjects will receive computer-based therapy, of increasing duration and intensity for up to 4 sessions/week for 8 weeks. The length of sessions will increase from 15 minutes in week 1 to 40 minutes of actual play in week 8. The longer sessions will also train cognitive endurance, or the ability for sustained cognitive effort. All experimental subjects will have their exercise duration and intensity data logged into the database and investigators will monitor them remotely. An Artificial Intelligence (AI) software layer in the system will progress game difficulty based on success in the games as well as on degree of cognitive engagement, as estimated by the biosensors. Higher cognitive difficulty will be indicative of improved cognition, thus progress in mitigating cognitive impairments subsequent to chemotherapy. Additionally, the duration of training will also be logged, as will be the frequency of training. Longer sessions will be indicative of ability to sustain cognitive engagement longer. Additional input will be obtained from caregivers in the form of periodic questionnaires.

Fatigue will be self-reported during weekly follow up calls by a Clinical Coordinator. Participants will train while seated, and (if needed) their arms can be supported on a table. Rest periods may be introduced as needed, to further mitigate fatigue.

At the end of every other week participants and their caregivers in the experimental group will fill a subjective evaluation questionnaire aimed at gauging perceived benefits and possible technical difficulties when using the BrightGo system. Questions will be scored on a 5-point Likert scale.

Control group will perform an equal amount of web-based game play of assigned cognitive-oriented games.

All participants will undergo screening for cognitive impairments (to confirm Mild Cognitive Impairment at baseline). Then they will continue with their daily routine during their 8-week training, and will undergo a second clinical evaluation at the end of these 8 weeks. All participants will then undergo a third (follow up) evaluation at 8 weeks post-end of training.

Caregivers will support the training by helping ensure compliance to protocol, and will complete subjective evaluation forms to rate the perceive benefit of training for the person they care for.

All participants will receive a weekly call from the Clinical Coordinator so to report on any health concerns and system issues.

Eligibility criteria: Recruitment will be at Robert Wood Johnson Medical School and at Rutgers NJ Cancer Institute.

INCLUSION CRITERIA FOR CANCER SURVIVORS WITH CRCI SUBSEQUENT TO CHEMOTHERAPY

* Female breast cancer survivor;
* Age 20 to 65 years;
* At least 12 years of formal education;
* Not participating in other studies;
* Generally healthy and active pre-diagnosis (based on self-report);
* Chemotherapy related cognitive impairments with a Montreal Cognitive Assessment (MoCA) Score 10-25 indicating mild to moderate impairment \[Chapman 2016\];
* Having had invasive (Stages II and III) breast cancer;
* Had completed standard course of chemotherapy with Anthracyclines: doxorubicin (Adriamycin) \& epirubicin (Ellence), or Taxanes: docetalex (Taxotere) \& paclitaxel (Taxol), or Combination therapies with like carboplatin, cyclophosphamide (Cytoxan), and fluorouracil (5-FU).
* At least one month post completion of first chemotherapy regimen.
* English speakers so as to comprehend game instructions, feedback forms, clinical exam questionnaires, and neuropsychological testing;
* Adult caregivers male or female can be either spouse, child, or a significant other living in the same home and available for the study;
* Absence of lymphedema or other co-morbidity limiting upper extremity function;
* Low propensity for simulation sickness (as measured by Simulation Sickness questionnaire);
* Living in the community in Central Jersey so to facilitate researchers travel to home for system installation and/or repairs,
* Living with a caregiver willing to support trials and be present during sessions;
* Good upper extremity motor function, able to move arms (at least 30 degrees shoulder, 30 degrees elbow and 30 degrees index finger); 20
* Willing to allow home inspections to ascertain internet conditions in the home, to determine best placement for the experimental system, to install and remove system, and to provide repairs if needed.

EXCLUSION CRITERIA FOR PARTICIPANTS WITH CRCI POST CHEMOTHERAPY

* Male;
* Female participants younger than 20 or older than 65;
* High propensity for simulation sickness (as determined by Simulation Sickness Questionnaire screening);
* Those with severe visual neglect or legally blind;
* Those with severe hearing loss or deafness;
* Those with uncontrolled hypertension (\>190/100 mmHg);
* Those with severe cognitive impairment (MoCA score\<10);
* Current diagnosis of moderate-severe depression (Beck Depression Inventory II score of 17-63);
* a history of psychiatric illness, defined as serious psychiatric illness such as bipolar mood disorder and schizophrenia, or requiring psychiatric hospitalization.
* a history of or current substance abuse;
* a previous head injury resulting in loss of consciousness;
* a prior diagnosis of neurological illness;
* a current or prior diagnosis of brain cancer;
* non-English speakers;
* Those unable to reliable participate in pre-study assessment due to any reason;
* Those with co-morbidities limiting arm and neck motor function (ex. lymphedema, chronic pain, severe arthritis);
* Less than 1 month post first chemotherapy regimen or starting chemotherapy during 16 weeks post screening (as chemotherapy during study participation is a confounding factor);
* Those with Stage IV (metastatic) breast cancer will be excluded;
* Those presenting with multiple cancers, such as breast and arm bone cancer, or breast and brain cancer;
* Those who are unwilling to allow a home inspection to ascertain Internet quality, determine best placement for the experimental or sham systems, for installation and removal of the systems and necessary repairs.

INCLUSION CRITERIA FOR CAREGIVERS OF PARTICIPANTS WITH CRCI POST CHEMOTHERAPY

* Age 18 or older;
* Generally in good overall health; 21
* Able to converse in English;
* Willing and able to participate in the study;
* Lives with the individual with CRCI post chemotherapy, or comes at least 4 days a week or at least present during home sessions;
* Willing to report on standard of care (e. g. any other treatments during the study) on a weekly basis while enrolled;
* Willing to report on experimental system issues and to fill periodic evaluation questionnaires.

EXCLUSION CRITERIA FOR CAREGIVERS OF INDIVIDUALS WITH CRCI POST CHEMOTHERAPY

* Cardiac, orthopedic, neurologic, psychiatric symptoms limiting participation;
* Dementia;
* Aggressive behaviors (observation);
* Domestic disputes or unstable home environment limiting home based training.

Reasons for exclusion based on these impairments relate to the nature of the virtual rehabilitation training, where participants need to be able to perceive the graphics scene on a head-mounted display, be able to hold game controllers in both hands and interact with therapeutic games, hear the simulation sounds, be aware of their surroundings and be able to sustain rapid arm/fingers movement. While the proposed system is considered safe, malignancies in the upper body, cardiac, orthopedic or neurologic issues can pose bodily risks due to intense activity, risks which we want to minimize. Pregnancy is an exclusion since pregnant women are more prone to simulation sickness. The evaluation instruments are in English, thus subjects who do not speak the language will not comprehend the evaluation questions or instructions, which will bias responses.

Primary outcomes:
measure: Change in Montreal Cognitive Assessment (MoCA)
timeFrame: Change from Screening at baseline, to 8 weeks and to 16 weeks from baseline
measure: Change in Test of Pre-morbid Functioning
timeFrame: Change from baseline, to 8 weeks and to 16 weeks from baseline
measure: Change in NAB Attention Module
timeFrame: Change from baseline, to 8 weeks and to 16 weeks from baseline
measure: Change in NAB Functioning Word Module
timeFrame: Change from baseline, to 8 weeks and to 16 weeks from baseline
measure: Change in Trail Making Test
timeFrame: Change from baseline, to 8 weeks and to 16 weeks from baseline
measure: Change in Hopkins Verbal Learning Test Revised
timeFrame: Change from baseline, to 8 weeks and to 16 weeks from baseline
measure: Change in Brief Visuo-spatial Memory Test, Revised (BVMT-R)
timeFrame: Change from baseline, to 8 weeks and to 16 weeks from baseline
Secondary outcomes:
measure: Change in Quality of Life Patient/Cancer Survivor Version (QOL-CSV)
timeFrame: Change from baseline, to 8 weeks and to 16 weeks from baseline
measure: Caregiver Quality of Life-Cancer (CQOL-C)
timeFrame: Change from baseline, to 8 weeks and to 16 weeks from baseline
measure: Change in Beck Depression Inventory II
timeFrame: Change from baseline, to 8 weeks and to 16 weeks from baseline
measure: Change in Grasp strength (Jamar dynamometer)
timeFrame: Change from baseline to 8 weeks and to 16 weeks from baseline
measure: Change in Shoulder strength (wrist weights)
timeFrame: Change from baseline, to 8 weeks and to 16 weeks from baseline
measure: Change in Range of motion (goniometer)
timeFrame: Change from baseline, to 8 weeks and to 16 weeks from baseline
measure: Change in Jebsen test of hand function
timeFrame: Change from baseline, to 8 weeks and to 16 weeks from baseline
measure: Change in Chedokee test (CAHAI-9)
timeFrame: Change from baseline, to 8 weeks and to 16 weeks from baseline
measure: Change in Game performance
timeFrame: Change in daily performance during 8 weeks experimental therapy
measure: Change in Subjective evaluation questionnaire
timeFrame: change in scores at 4 weeks and at 8 weeks from baseline
measure: biosensor data
timeFrame: at every session during 8 weeks experimental therapy following baselining
measure: Change in Subjective Pain Rating Scale
timeFrame: Change in subjective pain rating score from baslie to end of 8 weeks experimental therapy and at evaluation sessions
Other outcomes:
measure: Cyber-sickness Susceptibility Questionnaire for participant
timeFrame: Screening at consent
measure: Change in Heart rate
timeFrame: Change in heart rate from baseline to end of 8 week trainig measured every session.
measure: Change in Blood pressure (systolic and diastolic)
timeFrame: Change in heart rate from baseline to end of 8 week trainig measured every session.
Locations:
city: New Brunswick
country: United States
facility: Rutgers University Rober Wood Johnson Medical School
state: New Jersey
city: North Brunswick
country: United States
facility: Bright Cloud Int'l Corp
state: New Jersey
Study officials:
affiliation: Bright Cloud Int'l Corp
name: Grigore C Burdea, PhD
role: PRINCIPAL_INVESTIGATOR
References: