Improving Cognitive Function in Older Adults Undergoing Stem Cell Transplant

Multiple Myeloma Clinical Trial

— PROACTIVE  

Official title:

Promoting Physical Activity to Improve Cognitive Function in Older Adults Undergoing Hematopoietic Cell Transplantation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04898790
• Other study ID #: 0421-21-EP
• Status: Recruiting
• Phase: N/A
• Start date: November 18, 2021
• Est. completion date: April 2025

Study information

• Verified date: September 2023
• Source: University of Nebraska
• Contact: Marcia M Free, BSN
• Phone: 402-552-7623
• Email: marcia.free[@]unmc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Cancer and treatment-related cognitive changes 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. Physical activity improves cognitive function in older adults and survivors of other cancers. We hypothesize that increasing physical activity can also improve cognitive function in this vulnerable population. The objective of this research 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 60 years and older.

Aim 1: Adapt the CHAMPS-II manual and develop study materials using feedback from up to 10 patient/care-partner dyads who have experienced the HCT process within the last 3-6 months and HCT team members via semi-structured interviews. Aim 2: Iteratively adapt and implement CHAMPS-II intervention in three waves (2-6 patient/care-partner dyads per wave). The dyads will participate in a multi-phase, light to moderate-intensity physical activity program through Day 100 post-HCT. Aim 3: Test the preliminary effectiveness of the adapted intervention to improve cognitive function compared to a wait-list control condition (N = 34 per group) in a 2-arm, pilot randomized controlled trial.

Primary and secondary outcomes will include subjective and objective cognitive function using a short battery of neuropsychological tests and a self-report questionnaire. Tertiary outcomes comprise subjective and objective measures of physical activity behavior and physical function. The RE-AIM framework will be utilized for formative and process evaluation during the adaptation process and implementation of the intervention.

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.

The researcher will adapt CHAMPS II, an evidence-based physical activity intervention, to the HCT setting for older adults to improve cognitive function. CHAMPS II increased 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. 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, the research team 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 88
• Est. completion date: April 2025
• Est. primary completion date: April 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

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 exclusion criteria

Inclusion Criteria for Participants' Care-Partner:

• age 19 years and older

• able to speak and read English

Exclusion Criteria for Participants' Care-Partner:

• there are no exclusion criteria

Inclusion Criteria for Transplant Team Member:

• age 19 years and older

• able to speak and read English

Exclusion Criteria for Transplant Team Member:

• there are no exclusion criteria

Arms 2 and 3:

Inclusion Criteria for Participants:

• age 60 years and older

• have a diagnosis of hematological malignancy

• planned to receive an autologous or allogeneic HCT

• able to walk 4 meters as part of the Short Physical Performance Battery (with or without assistance)

• (In Arm 3 only): willingness to be randomized to either initiate the physical activity intervention pre-HCT or following Day 180 post-HCT, and to follow the protocol for the group to which they have been assigned

• able to speak and read English

• have provided written informed consent

Exclusion Criteria for Participants:

• development of chest pain, severe shortness of breath, or occurrence of other safety concerns during the physical performance measures (i.e. Short Physical Performance Battery)

• is not cleared to participate in exercise by a physician

Individuals with the following current conditions/diagnoses documented in medical history will be required to provide clearance for exercise from their cardiologist:

• Myocardial infarctions in the past 3 months

• Resting or unstable angina

• Uncontrolled and/or serious arrhythmias

• 3rd degree heart block

• Acute congestive heart failure or ejection fraction <30%

• Clinically significant aortic stenosis

Individuals with the following conditions/diagnoses will be required to provide clearance for exercise from their surgeon:

o Hip fracture, hip or knee replacement, or spinal surgery in the past 3 months

• other medical, psychiatric, or behavioral factors that in the judgement of the principal investigator may interfere with study participation or the ability to follow either the intervention or the active control condition

Inclusion Criteria for Participants' Care-Partner:

• age 19 years and older

• able to speak and read English

• able to walk 4 meters as part of the Short Physical Performance Battery (with or without assistance)

• have no medical contraindications for participating in light to moderate-intensity physical activity per PI review of medical history as reported on the care-partner medical history form

Exclusion Criteria for Participants' Care-Partner:

• development of chest pain, severe shortness of breath, or occurrence of other safety concerns during the physical performance measures (i.e. Short Physical Performance Battery)

• is not cleared to participate in exercise by a physician

Individuals with the following current conditions/diagnoses documented in medical history will be required to provide clearance for exercise from their cardiologist:

• Myocardial infarctions in the past 3 months

• Resting or unstable angina

• Uncontrolled and/or serious arrhythmias

• 3rd degree heart block

• Acute congestive heart failure or ejection fraction <30%

• Clinically significant aortic stenosis

Individuals with the following conditions/diagnoses will be required to provide clearance for exercise from their surgeon:

o Hip fracture, hip or knee replacement, or spinal surgery in the past 3 months

• other medical, psychiatric, or behavioral factors that in the judgement of the principal investigator may interfere with study participation or the ability to follow either the intervention or the active control condition

Inclusion Criteria for Transplant Team Member:

• age 19 years and older

• able to speak and read English

Exclusion Criteria for Transplant Team Member:

• there are no exclusion criteria

Related Conditions & MeSH terms

• Leukemia
• Lymphoma
• MDS
• Multiple Myeloma
• Myeloproliferative Disorders
• Myeloproliferative Neoplasm

Intervention

Behavioral:
• CHAMPS-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.

Locations

Country	Name	City	State
United States	University of Nebraska Medical Center	Omaha	Nebraska

Sponsors (1)

Lead Sponsor	Collaborator
University of Nebraska

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in functional ability as measured by the Short Performance Physical Battery (SPPB).	Change in total score, determined by objective measures of balance, gait speed and endurance with the Short Performance Physical Battery (SPPB). Minimum score is zero, maximum is 12; higher score means better outcome.	12 weeks
Other	Change in endurance as measured by the 6-minute walk.	Change in distance measured in meters, determined by a 6-minute walk. More distance in meters is better outcome.	12 weeks
Other	Change in performance of instrumental activities of daily living as measured by the Lawton Instrumental Activities of Daily Living (IADL).	Change in total score, determined by a self-report questionnaire: Lawton Instrumental Activities of Daily Living (Lawton IADL). Minimum score is zero, maximum is 8; higher score means better outcome.	12 weeks
Other	Change in physical activity as measured by the Community Healthy Activities Model Program for Seniors II (CHAMPS-II) questionnaire.	Change in total score of light and moderate physical activity as measured by a self-report questionnaire (CHAMPS-II questionnaire). Frequency and duration of various intensity activities and their caloric expenditure per week are all scored. No activity, duration or calories expended would be minimum score, and unlimited would be the maximum; where more frequency, duration and calories expended would be a better outcome.	12 weeks
Other	Change in physical activity as measured by the activePAL4 accelerometer data.	Change in time spent in upright postural allocation as measured by an accelerometer (activPAL4). Increased time in upright postural allocation is better outcome.	12 weeks
Primary	Change in executive function as measured by Trails A.	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.	12 weeks
Primary	Change in executive function as measured by Trails B.	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.	12 weeks
Primary	Change in executive function as measured by the Controlled Oral Word Association Test (COWAT).	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.	12 weeks
Primary	Change in working memory as measured by the Hopkins Verbal Learning Test-Revised (HVLT-R).	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.	12 weeks
Secondary	Change in global cognitive function as measured by the Montreal Cognitive Assessment (MoCA).	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.	12 weeks
Secondary	Change in subjective memory as measured by the Neuro-Quality of Life (QOL) Cognition Function-Short Form.	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.	12 weeks