Rehabilitation and Longitudinal Follow-up of Cognition in Adult Lower Grade Gliomas

University of California San Francisco (UCSF)

Status: Enrolling

Conditions: Low-grade Glioma

Treatments: Behavioral: In-person cognitive rehabilitation; Device: Healthy SMS texting; Behavioral: Telehealth cognitive rehabilitation; Device: ReMind iPad app

Study type: Interventional

Funder types: Other

Identifiers

NCT03948490

NCI-2019-03245 (Registry Identifier)

19103

Details and patient eligibility

About

Patients with glial brain tumors have increasingly improved outcomes, with median survival of 5-15 years. However, the treatments, including surgery, radiation, and chemotherapy, often lead to impaired attention, working memory, and other cognitive functions. These cognitive deficits frequently have significant impact on patient quality of life. Although currently, there is no established standard of care to treat cognitive deficits in brain tumor patients, standard cognitive rehabilitative treatments have been developed for those with traumatic brain injury and stroke. However, the feasibility and efficacy of these cognitive treatments in individuals with brain tumors remains unclear.

Full description

This trial studies how well cognitive rehabilitation therapy works in improving cognitive function in patients with lower grade gliomas. Patients with low grade gliomas frequently have symptoms of cognitive impairment, such as difficulty with short term memory and processing information, that impacts their daily lives. The ReMind application (app) is an iPad app developed for cognitive rehabilitation for patients. The healthy texting platform was developed to help patients with depression and cognitive difficulty to provide education and track their mood. Methods of cognitive rehabilitation therapy such as in person cognitive rehabilitation, computerized cognitive rehabilitation, and healthy text messaging may help improve cognition and quality of life in patient with low grade gliomas.

PRIMARY OBJECTIVES:

• Assess feasibility of each interventional arm independently (Arm 1)
• Detect a decline of >= 1.5 standard deviation (SD) from baseline on the Wechsler Adult Intelligence Scale (WAIS)- IV Working Memory Score or Hopkins Verbal Learning Test (HVLT) during the 36 month follow-up after surgery. (Arm 2)

SECONDARY OBJECTIVES:

• Measure changes in cognition at post-intervention and follow-up for each cohort - cohort 1 in-person; cohort 1A telehealth; cohort 2 ReMind; and cohort 3 short message service (SMS) texting - at 3 months and 6 months post-intervention. (Arm 1)
• Measure changes in health related quality of life (HRQOL) at post-intervention and follow-up for each cohort - cohort 1 in-person; cohort 2 ReMind; and cohort 3 SMS texting - as captured by Patient Reported Outcomes Measurement Information System-quality of life (PROMIS-QOL) - at 3 months and 6 months post-intervention. (Arm 1)
• Assess relationships between cognitive changes and clinical factors (molecular subtype, age, tumor location, treatment, and radiation fields when appropriate). (Arm 2)
• Assess relationships between cognitive changes and serial magnetic resonance (MR) imaging (T2 and contrast-enhancing tumor volume, diffusion tensor imaging (DTI) scalar quantification, structural connectivity, resting-state functional magnetic resonance imaging (fMRI) connectivity). (Arm 2)
• Assess relationships between HRQOL and cognitive changes. (Arm 2)

EXPLORATORY OBJECTIVES:

• Assess relationships between cognitive and HRQOL. (Arm 1)
• Assess relationships between cognitive changes and clinical factors (molecular subtype, age, tumor location, and radiation fields when appropriate). (Arm 1)
• Assess relationships between HRQOL changes and clinical factors (molecular subtype, age, tumor location, and radiation fields when appropriate). (Arm 1)
• Assess relationships between cognitive changes and serial MR imaging (T2 and contrast-enhancing tumor volume, DTI scalar quantification, structural connectivity, resting-state fMRI connectivity). (Arm 1)
• Identify predictive power of tumor characteristics (tumor volume, location, molecular characteristics), patient characteristics (extent of resection, treatment, and radiation fields when appropriate), imaging characteristics (e.g. fMRI, DTI changes), and decline in cognition or HRQOL. (Arm 2)

OUTLINE:

Patients are invited to participant in Cohort 1A. Patients unable to participant in Cohort 1A are randomized to Cohort 2 or Cohort 3.

ARM 1:

• COHORT 1 (CLOSED): Patients receive standard in-person cognitive rehabilitation sessions with a neuropsychologist every 2 weeks over 1 hour each for 12 weeks.
• COHORT 1A: Patients receive telehealth cognitive rehabilitation with University of California, San Francisco (UCSF) Zoom visits with a neuropsychologist who specializes in brain tumors over 60 minutes every 2 weeks for 3 months.
• COHORT 2 (CLOSED): Patients receive computerized cognitive rehabilitation using the ReMind app over 3 hours per week for 12 weeks.
• COHORT 3 (CLOSED): Patients receive healthy text messages daily at random points during the week (Monday - Friday) for 12 weeks.

ARM 2:

• COHORT 4: Patients who receive radiation after surgery, undergo longitudinal cognitive and health related quality of life assessments prior to surgery, prior to start of radiation, at 4-6 week after radiation, 6 and 12 months after surgery, and then every 6 months for 36 months after surgery.
• COHORT 5: Patients who do not receive radiation after surgery, undergo longitudinal cognitive and health related quality of life assessments prior to surgery, within 1 month after surgery, 2-4 months after surgery, 6 and 12 months after surgery, and then every 6 months for 36 months after surgery.

After completion of study, patients in cohorts 1-3 are followed up at 3 and 9 months.

Enrollment: 97 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Arm 1:

Inclusion Criteria:

• Histologically confirmed low grade supratentorial primary brain tumor
• >= 18 years old
• Life expectancy > 12 weeks
• Karnofsky performance status (KPS) >= 70
• Must speak and be able to read English fluently
• Must have access to the internet
• Must have text enabled cellphone
• Must be receiving MRI scans at University of California, San Francisco (UCSF)
• Must be clinically stable and off treatment (e.g. radiation or chemotherapy) for ≥ 3 months
• Must be >= 6 months from craniotomy
• Must have subjective complaints of cognitive deficits
• Must have adequate seizure control and be on a stable, or decreasing, dose of anti-epileptics
• Must score <= 1 SD below normal on ≥ 2 or more domains of baseline neuropsychological assessments

Exclusion Criteria:

• Diagnosis or evidence of any of the following:
• • Glioblastoma
• • Extra-axial disease (i.e. meningioma)
• • Infra-tentorial disease
• Are not able to comply with study and/or follow-up procedures
• Are unable to complete or score >= 3 cognitive tests at baseline, which is indicative that patients would be unable to complete the cognitive rehabilitation interventions
• Are acutely suicidal, psychotic, and/or gravely disabled.
• Patients who, based on the neuropsychologist's opinion, are unable to participate in cognitive testing and/or cognitive rehab secondary to significant neurologic deficit

Arm 2:

Inclusion Criteria:

• Have a presumed low grade primary brain tumor and either be undergoing definitive surgery or have had surgical resection within the last 4 months.
• Prior surgery is allowed if they have not received additional tumor directed treatment.
• >= 18 years old
• Must speak and be able to read English fluently.
• Plan to continue to care in neuro-oncology at UCSF
• Must be receiving MRI scans.

Exclusion Criteria:

• Diagnosis or evidence of any of the following:
• • Glioblastoma
• • Extra-axial disease (i.e. meningioma)
• Are not able to comply with study and/or follow-up procedures
• Have acute psychiatric issues (suicidality, active psychosis, gravely disabled)

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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97 participants in 6 patient groups

Arm 1 Cohort 1: Interventional arm/In-person rehab (CLOSED)

Other group

Description:

The in-person cognitive rehabilitation will focus on the application of evidenced based strategies recommended as practice guidelines by the American Congress of Rehabilitation Medicine Cognitive Rehabilitation Task Force (ACRM-CR). The treatment occurs in two stages 1) comprehensive neuropsychological assessment and rehabilitation planning and 2) implementation of treatment planning. n = 20 patients

Treatment:

Behavioral: In-person cognitive rehabilitation

Arm 1 Cohort 2: Interventional arm/ReMind iPad app (CLOSED)

Experimental group

Description:

The ReMind iPad-based cognitive rehabilitation was developed with collaborators at Tilburg University, The Netherlands, and is an evidence-based program to improve attention and memory through (1) cognitive training and (2) teaching compensatory skills in patients with brain tumors. Brain plasticity-based computerized cognitive training is a newly developing field of therapeutics for neurological and psychiatric disorders that uses frequent game-like training sessions to drive improvements in cognitive functions. n = 20 patients

Treatment:

Device: ReMind iPad app

Arm 1 Cohort 3: Interventional arm/Healthy SMS texting (CLOSED)

Experimental group

Description:

The mobile phone texting intervention was developed with collaborators at Zuckerberg San Francisco General Hospital and is currently being studied in individuals with depression and traumatic brain injury. Participants receive a daily message sent at a random time (within their chosen timeframe(s); e.g. 9am-9pm). Messages will focus on patient-based education-focused health-related quality of life and cognitive education such as internal and external cognitive compensatory strategy training, fatigue management, and coping skills. n = 20 patients

Treatment:

Device: Healthy SMS texting

Arm 2 Cohort 4: Longitudinal arm/Upfront radiation

No Intervention group

Description:

Patients will undergo longitudinal global cognitive and HRQOL assessments at baseline prior to surgery, after surgery, 3 months after surgery and every 6 months for 3 years. Clinical data will be collected at the time of each assessment. This will include changes in serial imaging e.g. in T2 tumor volume, DTI scalar quantification, resting-state fMRI connectivity n = 50 patients

Arm 1 Cohort 5: Longitudinal arm/No upfront radiation

No Intervention group

Description:

Patients will undergo longitudinal global cognitive and HRQOL assessments at baseline prior to surgery, after surgery, 3 months after surgery and every 6 months for 3 years. Clinical data will be collected at the time of each assessment. This will include changes in serial imaging e.g. in T2 tumor volume, DTI scalar quantification, resting-state fMRI connectivity n = 50 patients

Arm 1 Cohort 1A: Telehealth Cognitive Rehabilitation

Other group

Description:

The telehealth cognitive rehabilitation will take place over secure UCSF Zoom. It will focus on the application of evidenced based strategies recommended as practice guidelines by the American Congress of Rehabilitation Medicine Cognitive Rehabilitation Task Force (ACRM-CR). The treatment occurs in two stages 1) comprehensive neuropsychological assessment and rehabilitation planning and 2) implementation of treatment planning. During treatment implementation, patients acquire, apply, and adapt evidenced based strategies based on neuropsychological testing and conjointly developed treatment planning goals. N=20

Treatment:

Behavioral: Telehealth cognitive rehabilitation