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

Low-grade Glioma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03948490
• Other study ID #: 19103
• Secondary ID: NCI-2019-03245
• Status: Active, not recruiting
• Phase: N/A
• Start date: June 7, 2019
• Est. completion date: March 31, 2025

Study information

• Verified date: February 2024
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 67
• Est. completion date: March 31, 2025
• Est. primary completion date: March 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 at UCSF or have had surgical resection at UCSF within the last 3 months.

• Prior surgery is allowed if they are coming to UCSF for definitive surgery and have not received additional systemic treatment or radiation.

• >= 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)

Related Conditions & MeSH terms

• Glioma
• Low-grade Glioma

Intervention

Device:
• ReMind iPad app
Evidence-based program to improve attention and memory through (1) cognitive training and (2) teaching compensatory skills in patients with brain tumors.
• Healthy SMS texting
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.

Behavioral:
• In-person cognitive rehabilitation
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.
• Telehealth cognitive rehabilitation
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

Locations

Country	Name	City	State
United States	University of California, San Francisco	San Francisco	California

Sponsors (3)

Lead Sponsor	Collaborator
University of California, San Francisco	Tilburg University, University of California, Berkeley

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of subjects who complete all of the intervention exercises for each cohort (Arm 1)	The intervention will be considered feasible for a larger-scale efficacy study if greater than 80% of the subjects complete the intervention. Patients will be replaced if they drop out of the intervention (either by declining their first follow-up visit for Cohort 1 in-person rehab; declining to participate in the Cohort 2 ReMind intervention; or by texting the word "STOP" in the Cohort 3 short message service (SMS) texting intervention)) within the first 14 days. These patients will be replaced. All other patients will be evaluable for feasibility if they remain in the Cohort past the first 14 days of the intervention	9 months
Primary	Number of participants who show a decline of >= 1.5 SD from baseline on the Wechsler Adult Intelligence Scale IV (WAIS-IV) Working Memory Score or Hopkins Verbal Learning Test (HVLT) (Arm 2)	Detect a decline of greater than 1.5 standard deviation (SD) compared to baseline on WAIS-IV Working Memory Score or HVLT during the 36 month follow-up after surgery	3 years
Secondary	Improvement of =1.5 SD in at least one cognitive domain at post-intervention and/or follow-up for each Cohort (Arm 1)	Changes in cognitive domains overtime will focus on changes in WAIS-IV Working Memory Score from baseline to post-intervention and/or follow-up within each cohort with a goal to detect the first time point at which there is at least a 1.5 standard deviation difference from baseline average	9 months
Secondary	Improvement of =1.5 SD in health related quality of life (HRQOL) as measured by Patient-Reported Outcomes Measurement Information System (PROMIS-NeuroQOL) at post-intervention and/or follow-up for each Cohort (Arm 1)	Measure changes in HRQOL for each Arm 1 cohort - Cohort 1 in-person; Cohort 2 ReMind; and Cohort 3 SMS texting - as captured by Patient-Reported Outcomes Measurement Information System (PROMIS-QOL) - at post-intervention (3 months from baseline) and 6 months (9 months from baseline) post-intervention	9 months
Secondary	Assess relation ships between cognitive changes and clinical factors (Arm 2)	Identify clinical factors (molecular subtype, age, tumor location, treatment) that correlate with =1.5 SD in at least one cognitive domain	3 years
Secondary	Assess relationships between cognitive changes and serial magnetic resonance (MR) imaging (Arm 2)	Identify MR imaging characteristics (T2 FLAIR tumor volume at each imaging, T1 contrast enhancement volume at each imaging, Median, 10%, 90% apparent diffusion coefficient (ADC) and fractional anisotropy (FA) within T2 and T1 contrast tumor volumes, DTI scalar quantification and structural connectivity, Cerebral Blood Flow (CBF) within T2 and T1 contrast tumor volumes, Resting-state fMRI connectivity within the following major functional networks: default mode network, sensory/motor network, executive network, salience network, visual network and auditory network) at each time that correlate with >=1.5 SD in at least one cognitive domain.	3 years
Secondary	Correlation of PROMIS-NeuroQOL scores and cognitive changes (Arm 2)	The changes in HRQOL as measured by PROMIS-NeuroQOL will be correlated using Spearman's rank correlation changes in >=1.5 standard deviation on at least one cognitive domain. The PROMIS-NeuroQOL is a 5 item scale which measures how much difficulty specific tasks are to complete. Item scores range from 5="None" to 1="Cannot do". The Spearman's correlation coefficient (rs) measures the strength and direction of association between two variables and can take values from +1 to -1 where a value of +1 indicates a perfect association, an rs of 0 indicates no association and an rs of -1 indicates a perfect negative association. The closer rs is to 0, the weaker the association.	3 years
Secondary	Correlation between isodose lines and cognitive changes (Arm 2)	The isodose lines for patients who received radiation will be correlated using Spearman's rank correlation with changes in >=1.5 standard deviation on at least one cognitive domain. The Spearman's correlation coefficient (rs) measures the strength and direction of association between two variables and can take values from +1 to -1 where a value of +1 indicates a perfect association, an rs of 0 indicates no association and an rs of -1 indicates a perfect negative association. The closer rs is to 0, the weaker the association.	3 years