Physiological Stress
Conditions
Keywords
exercise, stress management, post transplant, physical and emotional relaxation
Brief summary
This is a Phase III, randomized, unblinded, multicenter, prospective comparative study. The purpose of this study is to test whether exercise or stress management training delivered to autologous and allogeneic hematopoietic cell transplantation (HCT) patients prior to transplantation can improve functional status and the transplant experience.
Detailed description
Background: The adverse effects of hematopoietic cell transplantation (HCT) on short and long term quality of life are well documented. Patients experience numerous aversive symptoms (e.g., nausea, fatigue, and sleep disturbance) that are accompanied by declines in physical and mental well-being. Although most longitudinal studies show return to baseline functioning for the majority of patients, it may take 6 to 12 months or longer to reach this goal. Clinical trials have shown that training in stress management techniques and participation in formal exercise programs each offered in isolation are effective in improving quality of life in patients receiving standard-dose chemotherapy and HCT. Review of these studies suggests that stress management interventions primarily improve mental health outcomes and nausea. The impact of exercise training interventions is more variable; most studies report physical health benefits, with some studies also reporting mental health benefits. Small studies suggest that combining stress management training and exercise are feasible and well-tolerated, but whether the combination provides an additive or synergistic impact on quality of life outcomes has not been directly investigated. Design Narrative: The protocol is designed as a factorial trial with two interventions, exercise and stress management, which results in four treatment arms: standard care, exercise only, stress management only and the combination of exercise and stress management. The primary objective of this randomized phase III trial is to test the ability of exercise training or stress management training to improve physical and mental functioning at Day 100 post hematopoietic cell transplantation.
Interventions
BEHAVIORALExercise
Participants assigned to the Exercise arm will receive a packet of materials from the study interventionist, along with a brief personalized introduction to the home-based exercise intervention.
BEHAVIORALStress Management
Participants will receive a packet of materials from the study interventionist, along with a brief (10 minute) standardized introduction to the self-administered intervention.
BEHAVIORALExercise and Stress Management
Participants will receive a packet of materials from the study interventionist, along with a brief (15 minute) personalized introduction to the interventions.
OTHERStandard Care
Patients randomized to standard care only will be informed of their assigned condition and receive the DVD.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Blood and Marrow Transplant Clinical Trials Network
National Cancer Institute (NCI)
National Marrow Donor Program
Medical College of Wisconsin
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 years or older * Able to speak and read English * Able to exercise at low to moderate intensity - adequate cardiopulmonary reserve, as judged by self-reported ability to walk up one flight of stairs, no requirement for supplemental oxygen, and physician judgment * Willing and able to provide informed consent. * Stated willingness to comply with study procedures and reporting requirements * Planned autologous or allogeneic transplantation within 6 weeks.
Exclusion criteria
* Orthopedic, neurologic or other problems which prevent safe ambulation and protocol adherence * Participation in another clinical trial with quality of life or functional status as a primary endpoint
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Functional Status | 100 days | To determine whether exercise or stress management improves self-reported physical and mental functioning compared to standard care at 100 days post hematopoietic cell transplantation (HCT) using evaluated patients. The Physical Component Score (PCS) and Mental Component Score (MCS) of the SF-36 will be the primary endpoint measures of functional status. Raw scores are converted to a standard metric (0-100), with higher scores being indicative of a better health state. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cancer and Treatment Distress (CTXD) | 100 days | Cancer and treatment distress will be measured by the acute version of the Cancer and Treatment Distress (CTXD) scale, a 27 item validated measure of distress with domains of Uncertainty, Health Burden, Family Strain, Identity and Managing the Medical System used extensively in HCT studies. The scale ranges from 0 - 3, where a higher score reflects more distress. |
| The Pittsburgh Sleep Quality Index (PSQI) | 100 days | The Pittsburgh Sleep Quality Index (PSQI) is a widely used seven item self-report measure of sleep patterns and difficulties. A modified version will be used to obtain self-reports of the following for the past week: sleep quality, sleep latency, sleep efficiency, and use of sleeping medications. The scale ranges from 0 - 21, where a higher score reflects worse sleep quality. |
| Nausea | 100 days | Two questions using a similar format as the SF-36 were added to measure nausea. The scale ranges from 1 - 5, where a higher score indicates worse nausea. |
| Symptoms | 100 days | Patients will complete the MOS 36-Item Short Form (SF-36), a widely used self-report measure designed to assess perceived health and functioning, contains eight scales: Physical Functioning (PF), Role-Physical (R-P); Bodily Pain (BP); General Health (GH); Vitality (VT); Social Functioning (SF); Mental Health (MH); and Role-Emotional (R-E). Scales are comprised of different numbers of items and use a variety of rating formats. Raw scores are converted to a standard metric (0-100), with higher scores being indicative of a better health state. |
| SF-36 Late Outcomes | 6 months | The SF-36 PCS and MCS will be collected from participants at six months. Raw scores are converted to a standard metric (0-100), with higher scores being indicative of a better health state. |
| Survival | 6 months and 1 year | Both survival at 6 months and overall survival at last follow-up will be reported. Overall survival is defined as the interval between transplantation and death or last follow-up. Patients alive when the study closes or lost to follow up are censored at the date of last contact. |
| Days of Hospitalization | 100 days | The number of hospital days within the first 100 days after graft infusion will be collected for patients surviving at least 100 days. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Exercise Participants assigned to the Exercise arm will receive a packet of materials from the study interventionist, along with a brief personalized introduction to the home-based exercise intervention. | 180 |
| Stress Management Participants will receive a packet of materials from the study interventionist, along with a brief (10 minute) standardized introduction to the self-administered intervention. | 178 |
| Exercise and Stress Management Participants will receive a packet of materials from the study interventionist, along with a brief (15 minute) personalized introduction to the interventions. | 178 |
| Standard Care Patients randomized to standard care only will be informed of their assigned condition and receive the DVD. | 175 |
| Total | 711 |
Baseline characteristics
| Characteristic | Exercise | Total | Standard Care | Exercise and Stress Management | Stress Management |
|---|---|---|---|---|---|
| Age, Customized <=40 years | 26 participants | 100 participants | 27 participants | 26 participants | 21 participants |
| Age, Customized 41-<65 years | 105 participants | 457 participants | 111 participants | 118 participants | 123 participants |
| Age, Customized >=65 years | 49 participants | 154 participants | 37 participants | 34 participants | 34 participants |
| Disease AML/ANLL/ALL | 42 participants | 171 participants | 42 participants | 40 participants | 47 participants |
| Disease CLL/SLL | 5 participants | 20 participants | 7 participants | 5 participants | 3 participants |
| Disease CML | 5 participants | 14 participants | 2 participants | 2 participants | 5 participants |
| Disease Lymphoma | 54 participants | 230 participants | 50 participants | 66 participants | 60 participants |
| Disease MDS/MPS | 19 participants | 63 participants | 13 participants | 15 participants | 16 participants |
| Disease Missing | 1 participants | 5 participants | 1 participants | 3 participants | 0 participants |
| Disease MM/PCD | 50 participants | 196 participants | 57 participants | 45 participants | 44 participants |
| Disease Other Disease | 1 participants | 1 participants | 0 participants | 0 participants | 0 participants |
| Disease SAA | 3 participants | 9 participants | 2 participants | 2 participants | 2 participants |
| Disease Solid Tumors | 0 participants | 2 participants | 1 participants | 0 participants | 1 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 35 Participants | 6 Participants | 11 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 172 Participants | 673 Participants | 167 Participants | 167 Participants | 167 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 3 Participants | 2 Participants | 0 Participants | 0 Participants |
| Karnofsky Performance-status Score 50%-60% | 2 participants | 10 participants | 4 participants | 3 participants | 1 participants |
| Karnofsky Performance-status Score 70%-80% | 65 participants | 273 participants | 68 participants | 76 participants | 64 participants |
| Karnofsky Performance-status Score >=90% | 112 participants | 419 participants | 102 participants | 94 participants | 111 participants |
| Karnofsky Performance-status Score Missing/Not done | 1 participants | 9 participants | 1 participants | 5 participants | 2 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 11 Participants | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants | 60 Participants | 16 Participants | 13 Participants | 17 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 6 Participants | 3 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 3 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 4 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) White | 162 Participants | 626 Participants | 152 Participants | 160 Participants | 152 Participants |
| Sex: Female, Male Female | 68 Participants | 306 Participants | 82 Participants | 78 Participants | 78 Participants |
| Sex: Female, Male Male | 112 Participants | 405 Participants | 93 Participants | 100 Participants | 100 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 178 | 0 / 175 | 0 / 174 | 0 / 174 |
| serious Total, serious adverse events | 0 / 178 | 0 / 175 | 1 / 174 | 0 / 174 |
Outcome results
Primary
Functional Status
To determine whether exercise or stress management improves self-reported physical and mental functioning compared to standard care at 100 days post hematopoietic cell transplantation (HCT) using evaluated patients. The Physical Component Score (PCS) and Mental Component Score (MCS) of the SF-36 will be the primary endpoint measures of functional status. Raw scores are converted to a standard metric (0-100), with higher scores being indicative of a better health state.
Time frame: 100 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Exercise | Functional Status | MCS | 50.8 units on a scale | Standard Deviation 10.44 |
| Exercise | Functional Status | PCS | 42.2 units on a scale | Standard Deviation 10.47 |
| Stress Management | Functional Status | PCS | 41.8 units on a scale | Standard Deviation 9.59 |
| Stress Management | Functional Status | MCS | 52.4 units on a scale | Standard Deviation 9.43 |
| Exercise and Stress Management | Functional Status | PCS | 40.6 units on a scale | Standard Deviation 10.49 |
| Exercise and Stress Management | Functional Status | MCS | 52.1 units on a scale | Standard Deviation 9.7 |
| Standard Care | Functional Status | MCS | 50.4 units on a scale | Standard Deviation 10.69 |
| Standard Care | Functional Status | PCS | 42.5 units on a scale | Standard Deviation 9.22 |
Secondary
Cancer and Treatment Distress (CTXD)
Cancer and treatment distress will be measured by the acute version of the Cancer and Treatment Distress (CTXD) scale, a 27 item validated measure of distress with domains of Uncertainty, Health Burden, Family Strain, Identity and Managing the Medical System used extensively in HCT studies. The scale ranges from 0 - 3, where a higher score reflects more distress.
Time frame: 100 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Exercise | Cancer and Treatment Distress (CTXD) | 0.96 units on a scale | Standard Deviation 0.56 |
| Stress Management | Cancer and Treatment Distress (CTXD) | 0.88 units on a scale | Standard Deviation 0.6 |
| Exercise and Stress Management | Cancer and Treatment Distress (CTXD) | 1.04 units on a scale | Standard Deviation 0.66 |
| Standard Care | Cancer and Treatment Distress (CTXD) | 0.94 units on a scale | Standard Deviation 0.57 |
Secondary
Days of Hospitalization
The number of hospital days within the first 100 days after graft infusion will be collected for patients surviving at least 100 days.
Time frame: 100 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Exercise | Days of Hospitalization | 21.1 days | Standard Deviation 20.3 |
| Stress Management | Days of Hospitalization | 22.7 days | Standard Deviation 19.6 |
| Exercise and Stress Management | Days of Hospitalization | 21.6 days | Standard Deviation 20.6 |
| Standard Care | Days of Hospitalization | 20.9 days | Standard Deviation 17 |
Secondary
Nausea
Two questions using a similar format as the SF-36 were added to measure nausea. The scale ranges from 1 - 5, where a higher score indicates worse nausea.
Time frame: 100 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Exercise | Nausea | 2.74 units on a scale | Standard Deviation 1.38 |
| Stress Management | Nausea | 2.63 units on a scale | Standard Deviation 1.41 |
| Exercise and Stress Management | Nausea | 2.80 units on a scale | Standard Deviation 1.47 |
| Standard Care | Nausea | 2.85 units on a scale | Standard Deviation 1.49 |
Secondary
SF-36 Late Outcomes
The SF-36 PCS and MCS will be collected from participants at six months. Raw scores are converted to a standard metric (0-100), with higher scores being indicative of a better health state.
Time frame: 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Exercise | SF-36 Late Outcomes | PCS | 44.5 units on a scale | Standard Deviation 9.4 |
| Exercise | SF-36 Late Outcomes | MCS | 51.6 units on a scale | Standard Deviation 9.8 |
| Stress Management | SF-36 Late Outcomes | MCS | 52.5 units on a scale | Standard Deviation 9.1 |
| Stress Management | SF-36 Late Outcomes | PCS | 42.3 units on a scale | Standard Deviation 10.6 |
| Exercise and Stress Management | SF-36 Late Outcomes | MCS | 50.7 units on a scale | Standard Deviation 11 |
| Exercise and Stress Management | SF-36 Late Outcomes | PCS | 43.4 units on a scale | Standard Deviation 10 |
| Standard Care | SF-36 Late Outcomes | PCS | 42.8 units on a scale | Standard Deviation 10.1 |
| Standard Care | SF-36 Late Outcomes | MCS | 51.7 units on a scale | Standard Deviation 9.9 |
Secondary
Survival
Both survival at 6 months and overall survival at last follow-up will be reported. Overall survival is defined as the interval between transplantation and death or last follow-up. Patients alive when the study closes or lost to follow up are censored at the date of last contact.
Time frame: 6 months and 1 year
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Exercise | Survival | 6 months | 89 percentage of participants |
| Exercise | Survival | 1 year | 85 percentage of participants |
| Stress Management | Survival | 1 year | 82 percentage of participants |
| Stress Management | Survival | 6 months | 89 percentage of participants |
| Exercise and Stress Management | Survival | 6 months | 86 percentage of participants |
| Exercise and Stress Management | Survival | 1 year | 72 percentage of participants |
| Standard Care | Survival | 6 months | 92 percentage of participants |
| Standard Care | Survival | 1 year | 79 percentage of participants |
Secondary
Symptoms
Patients will complete the MOS 36-Item Short Form (SF-36), a widely used self-report measure designed to assess perceived health and functioning, contains eight scales: Physical Functioning (PF), Role-Physical (R-P); Bodily Pain (BP); General Health (GH); Vitality (VT); Social Functioning (SF); Mental Health (MH); and Role-Emotional (R-E). Scales are comprised of different numbers of items and use a variety of rating formats. Raw scores are converted to a standard metric (0-100), with higher scores being indicative of a better health state.
Time frame: 100 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Exercise | Symptoms | Vitality | 54.91 units on a scale | Standard Deviation 20.84 |
| Exercise | Symptoms | Mental Health | 76.68 units on a scale | Standard Deviation 17.24 |
| Exercise | Symptoms | Bodily Pain | 67.78 units on a scale | Standard Deviation 24.74 |
| Exercise | Symptoms | Social Functioning | 73.83 units on a scale | Standard Deviation 25.89 |
| Exercise | Symptoms | Role Physical | 54.79 units on a scale | Standard Deviation 30.21 |
| Exercise | Symptoms | Role Emotional | 81.73 units on a scale | Standard Deviation 25.64 |
| Exercise | Symptoms | General Health | 63.62 units on a scale | Standard Deviation 19.93 |
| Exercise | Symptoms | Physical Functioning | 66.46 units on a scale | Standard Deviation 24.47 |
| Stress Management | Symptoms | General Health | 60.05 units on a scale | Standard Deviation 19.86 |
| Stress Management | Symptoms | Vitality | 58.13 units on a scale | Standard Deviation 18.29 |
| Stress Management | Symptoms | Physical Functioning | 66.12 units on a scale | Standard Deviation 23.95 |
| Stress Management | Symptoms | Role Physical | 53.49 units on a scale | Standard Deviation 30.72 |
| Stress Management | Symptoms | Social Functioning | 76.13 units on a scale | Standard Deviation 26.52 |
| Stress Management | Symptoms | Bodily Pain | 71.55 units on a scale | Standard Deviation 25.17 |
| Stress Management | Symptoms | Mental Health | 80.17 units on a scale | Standard Deviation 15.29 |
| Stress Management | Symptoms | Role Emotional | 80.44 units on a scale | Standard Deviation 26.83 |
| Exercise and Stress Management | Symptoms | General Health | 58.06 units on a scale | Standard Deviation 20.25 |
| Exercise and Stress Management | Symptoms | Physical Functioning | 65.83 units on a scale | Standard Deviation 23.34 |
| Exercise and Stress Management | Symptoms | Social Functioning | 72.64 units on a scale | Standard Deviation 26.96 |
| Exercise and Stress Management | Symptoms | Role Physical | 54.74 units on a scale | Standard Deviation 29.33 |
| Exercise and Stress Management | Symptoms | Bodily Pain | 67.96 units on a scale | Standard Deviation 26.18 |
| Exercise and Stress Management | Symptoms | Vitality | 54.42 units on a scale | Standard Deviation 21.03 |
| Exercise and Stress Management | Symptoms | Role Emotional | 86.68 units on a scale | Standard Deviation 21.23 |
| Exercise and Stress Management | Symptoms | Mental Health | 77.85 units on a scale | Standard Deviation 17.58 |
| Standard Care | Symptoms | General Health | 59.43 units on a scale | Standard Deviation 19.38 |
| Standard Care | Symptoms | Bodily Pain | 68.19 units on a scale | Standard Deviation 24.15 |
| Standard Care | Symptoms | Physical Functioning | 67.38 units on a scale | Standard Deviation 24.3 |
| Standard Care | Symptoms | Role Emotional | 81.83 units on a scale | Standard Deviation 25.29 |
| Standard Care | Symptoms | Role Physical | 58.51 units on a scale | Standard Deviation 26.98 |
| Standard Care | Symptoms | Mental Health | 76.75 units on a scale | Standard Deviation 17.59 |
| Standard Care | Symptoms | Vitality | 53.56 units on a scale | Standard Deviation 21.06 |
| Standard Care | Symptoms | Social Functioning | 72.67 units on a scale | Standard Deviation 26.68 |
Secondary
The Pittsburgh Sleep Quality Index (PSQI)
The Pittsburgh Sleep Quality Index (PSQI) is a widely used seven item self-report measure of sleep patterns and difficulties. A modified version will be used to obtain self-reports of the following for the past week: sleep quality, sleep latency, sleep efficiency, and use of sleeping medications. The scale ranges from 0 - 21, where a higher score reflects worse sleep quality.
Time frame: 100 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Exercise | The Pittsburgh Sleep Quality Index (PSQI) | 4.55 units on a scale | Standard Deviation 3.5 |
| Stress Management | The Pittsburgh Sleep Quality Index (PSQI) | 3.49 units on a scale | Standard Deviation 2.93 |
| Exercise and Stress Management | The Pittsburgh Sleep Quality Index (PSQI) | 4.44 units on a scale | Standard Deviation 3.31 |
| Standard Care | The Pittsburgh Sleep Quality Index (PSQI) | 4.02 units on a scale | Standard Deviation 3.13 |