Leukemia, Lymphoma, Multiple Myeloma, Myelodysplastic Syndromes (MDS), Myeloproliferative Neoplasm
Conditions
Keywords
Hematopoietic cell transplantation
Brief summary
Cancer and treatment-related cognitive changes, such as thinking or remembering, hinder resumption of normal routine and roles and worsen quality of life. Older adults undergoing hematopoietic cell transplantation (HCT) are at high-risk for cognitive impairment. Age is a risk factor for Alzheimer's Dementia (AD) and the hematological malignancies leading to HCT. There are shared mechanisms and interactions between AD and cancer-related cognitive decline (CRCD). Physical activity improves cognitive function in older adults and survivors of other cancers. This study hypothesizes that increasing physical activity can also improve cognitive function in this vulnerable population. The study has two goals. The first is to adapt and test an evidence-based physical activity intervention, The Community Health Activities Model Program for Seniors II (CHAMPS II), in the HCT setting for adults 55 years and older. This will be done using semi-structured interview of up to 10 patients who have experienced the HCT process within the last 3 to 6 months with HCT care-team partners. The second goal will explore the prevalence and impact of AD-neuropathology and inflammation on cancer-related cognitive decline (CRCD) in older adults undergoing HCT.
Detailed description
Hematologic malignancies are diseases that primarily affect older adults, with a median age at diagnosis of 65 years. Hematopoietic cell transplantation (HCT) is a potentially curative and life-prolonging treatment for patients with hematologic malignancies. Cancer and treatment-related cognitive changes cause distress, hinder resumption of normal routine and roles, and worsen quality of life. HCT differs from the delivery of chemotherapy in other cancer settings due to the intensity of chemotherapy and severity of toxicity. Older adults undergoing HCT are at high risk for cognitive decline and pervasive cognitive deficits. Interventions to improve cognitive outcomes are needed. The prevalence and risk of cognitive decline post-HCT are greater for older adults because of a greater number of existing health conditions (i.e., vascular disease) and impaired physical and psychologic function pre-HCT that can be exacerbated by treatment and the overall HCT experience. Exercise training improves cancer-related health outcomes, including cardiorespiratory fitness, inflammation, cancer related fatigue, depressive symptoms, and sleep disturbance. There is consistent evidence showing that physical activity improves cognitive function in older adults and survivors of other cancers. Improvement in cardiorespiratory fitness, brain structure, and inflammation underlie the mechanisms of the cognitive benefits of physical activity. While untested in older adults undergoing HCT, the investigator hypothesizes that increasing physical activity can also improve cognitive function in this vulnerable population. Physical activity improves the cognitive domains most affected by cancer treatment, namely executive function and working memory. Cognitive function is an important outcome to older adults and has not been a focus of physical activity interventions in the HCT population. In addition, older adults are underrepresented in previous physical activity interventions in the HCT population. Investigators will adapt CHAMPS II, an evidence-based physical activity intervention, to the HCT setting for older adults to improve cognitive function. This is an individually tailored program that provides information, skills, training, and problem-solving support to older adults. The program provides a foundation for application by including an instructor manual and directions for implementation. CHAMPS-II has been adapted and implemented in diverse communities using existing resources and improving contextual factors to increase physical activity for sedentary older adults. Adaptation of evidence-based interventions, such as CHAMPS-II, can result in an attenuation of effects if the core components are not maintained. However, adaptations can be made to fit the needs and priorities of the service setting, target audience, mode of delivery, and cultural context without compromising CHAMPS-II effectiveness. Through a research-practice partnership approach, investigators will help adapt the program while maintaining the core components of CHAMPS-II, develop new program materials, provide training, monitor implementation, and conduct program evaluation. The overarching goal is to enable HCT team members to implement CHAMPS-II and leverage existing organizational resources to enhance feasibility and sustainability. The research plan proposes a hybrid effectiveness-implementation design, which is a design that spans the effectiveness and implementation research to accelerate the translation of physical activity interventions into practice for older adults with cancer. This novel trial design will allow testing of the program within a randomized clinical trial methodology while observing and gathering information on implementation. The effectiveness study condition offers an ideal opportunity to examine implementation issues and plan for implementation strategies for a future study that examines both effectiveness and implementation strategies. The study will use the RE-AIM (Reach, Effectiveness - Adoption, Implementation, and Maintenance) framework for planning and formative and process evaluation of the intervention. Formative and process evaluation provides information needed to evaluate an intervention's potential for translation into clinical practice. Investigators aim to understand the prevalence and impact of AD-neuropathology and inflammation on cognitive function and structural brain changes in older adults undergoing HCT. Quantifiable AD-related neuropathology can accumulate silently for decades with no clinical symptoms. Some will have no AD pathology, some will have "silent" AD pathology, and some will have clinically relevant levels of AD pathology. Brain volumes is also a measure of cognitive reserve with many factors that could impact brain volumes including aging, AD, other degenerative diseases, untreated obstructive sleep apnea (OSA), chronic stress, and ethyl alcohol or ethanol abuse (ETOH). Some patients with low brain volumes may have negative AD biomarkers. However, brain volumes may be a good predictor of CRCD. Investigators expect to gain an understanding of the prevalence of between-subject variability in the quantity of AD neuropathology and differences in brain volume. The results of this research will lay the groundwork for future funding opportunities to elucidate the bidirectional mechanisms, prevention and treatment of AD and CRCD in this population.
Interventions
BEHAVIORALCHAMPS-II adapted to adults 60+ years in HCT setting
CHAMPS-II is an evidence-based physical activity program designed to increase physical activity in sedentary older adults with multiple chronic health conditions. This is an individually tailored program that provides information, skills, training, and problem-solving support to older adults. Participants will engage in progressive, light to moderate-intensity physical activity throughout the HCT process, with the support of physical therapists, physical activity counselors, and their care-partner. They will take part in supervised exercise sessions; unsupervised exercise sessions; counseling sessions to address barriers, motivators, goals, and safety; and receive telephone support. Walking is the primary mode of aerobic activity, with training in flexibility, strengthening and balance exercises also included. An exercise kit will be provided, consisting of an intervention workbook, therapeutic resistance bands, and activity logs.
Sponsors
University of Nebraska
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
SINGLE (Outcomes Assessor)
Masking description
The outcomes assessor completing primary outcome testing during the RCT in Aim 3 will be blinded.
Intervention model description
Aim 1 will seek feedback from 1)adult participants 60+ years who have recently undergone HCT, 2)participants' care-partner, and 3)HCT team members for preliminary adaptation of the evidence-based physical activity intervention (CHAMPS-II) manual, and development of study materials. Aim 2 will iteratively adapt and implement CHAMPS-II for adults 60 years and older undergoing HCT with feedback from 1)adult participants 60+ years receiving HCT, 2)participants' care-partner, and 3)HCT team members. Aim 3 will take the final CHAMPS-II adaptation from Aim 2 and pilot test it, using a Type 1 hybrid effectiveness-implementation design to determine its preliminary effectiveness to improve cognitive function compared to a wait-list control condition. Feedback will be obtained on the intervention and control condition from 1)adult participants 60+ years receiving HCT, 2)participants' care-partner, and 3)HCT team members.
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Arm 1: Inclusion Criteria for Participants: * age 60 years and older * have a diagnosis of hematological malignancy * have received autologous or allogeneic HCT within the prior 3-6 months * able to speak and read English * have provided written informed consent
Exclusion criteria
for Participants: * there are no
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in executive function as measured by Trails A. | 12 weeks | Change in raw scores and z-scores, determined by the following neuropsychological test: Trail Making Test Part A (Trails A). Time to complete and number of errors are measured, where less time and errors are better outcomes. |
| Change in executive function as measured by Trails B. | 12 weeks | Change in raw scores and z-scores, determined by the following neuropsychological tests: Trail Making Test Part B (Trails B). Time to complete and number of errors are measured, where less time and errors are better outcomes. |
| Change in executive function as measured by the Controlled Oral Word Association Test (COWAT). | 12 weeks | Change in raw scores and z-scores, determined by the following neuropsychological test: Controlled Oral Word Association Test (COWAT). Minimum score is zero and maximum is unlimited; higher score means better outcome. |
| Change in working memory as measured by the Hopkins Verbal Learning Test-Revised (HVLT-R). | 12 weeks | Change in raw scores and z-scores, determined by the following neuropsychological test: Hopkins Verbal Learning Test-Revised (HVLT-R). There are 3 learning trials and 1 delayed recall trial. Minimum score for each is zero and maximum is 12; higher score means better outcome. There is also a delayed recognition trial where person is presented with both true positives and false positives. Minimum score for both is zero and maximum is 12. For the true positives a higher score means better outcome. For the false positives a lower score means better outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in global cognitive function as measured by the Montreal Cognitive Assessment (MoCA). | 12 weeks | Change in total score, determined by objective measures of global cognitive function using the Montreal Cognitive Assessment (MoCA). Minimum score is zero and maximum is 30; higher score means better outcome. |
| Change in subjective memory as measured by the Neuro-Quality of Life (QOL) Cognition Function-Short Form. | 12 weeks | Change in total score, determined by patient questionnaire: Neuro-Quality of Life (QOL) Cognition Function-Short Form. Minimum score is 8 and maximum score is 40; higher score means better outcome. |
Countries
United States
Contacts
CONTACTMarcia M Free, BSN
CONTACTThuy Koll, MD
PRINCIPAL_INVESTIGATORThuy Koll, MD
University of Nebraska
Outcome results
None listed