Fatigue
Conditions
Keywords
Older, Cancer, Survivors
Brief summary
The purpose of this research is to see if muscadine grape extract improves fatigue in people age 70 and above who have a history of treated cancer and report the symptom of fatigue.
Detailed description
Primary Objective: To evaluate whether administration of MGE supplementation decreases PROMIS Fatigue score from baseline to 12 weeks compared to placebo. Secondary Objective(s) * To evaluate whether administration of muscadine grape extract supplementation (4 tablets twice daily) causes changes in physical function (Pepper Assessment Tool for Disability \[PAT-D\], Short Physical Performance Battery), physical fitness (6-minute walk), physical activity (Minnesota Leisure Questionnaire), sedentary behavior (Sedentary Behavior Questionnaire) from baseline to 12 weeks compared to placebo. * To compare changes in health related quality of life (PROMIS Global Health) at 12 weeks in participants randomized to muscadine grape extract group vs. placebo. * To compare changes in the Fried frailty index at 12 weeks in participants randomized to muscadine grape extract vs. placebo. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive muscadine grape extract orally (PO) twice daily (BID) for 12 weeks in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive placebo PO BID for 12 weeks in the absence of disease progression or unacceptable toxicity. After completion of study, patients are followed up for 30 days after the last dose of the study drug.
Interventions
DIETARY_SUPPLEMENTMuscadine grape extract
Four pills twice daily
DRUGPlacebo
Four pills twice daily.
OTHERQuality of Life Assessment
Ancillary studies
OTHERQuestionnaires
Ancillary studies
OTHERParticipant Feedback
Ancillary studies
Sponsors
National Center for Advancing Translational Sciences (NCATS)
National Cancer Institute (NCI)
Wake Forest University Health Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Masking description
This is a double blind study. Only the investigational pharmacists and the statisticians will be unblinded. The blind will be maintained until the study is complete.
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Self-reported history of cancer diagnosed \> 12 months prior to enrollment excluding non-melanoma skin cancer with no evidence of disease at enrollment. * Eligible solid tumor cancer types include Stage 1-3 breast, lung, head and neck, colorectal, anal, prostate, melanoma, bladder/ureteral, esophageal, gastric, pancreatic, kidney, liver/biliary, uterine, cervical, ovarian, sarcoma. (superficial disease and in situ disease only is excluded) * Eligible hematologic malignancies include lymphoma any subtype any stage in remission, multiple myeloma in remission, leukemia any subtype in remission. * Eligible prior cancer treatment modalities include surgery, radiation, chemotherapy, hormonal therapies, immunotherapy, biologic therapies. * All anti-cancer therapy completed \> 12 months prior to enrollment * Age 65 years and older * Presence of self-reported fatigue defined by a response of somewhat, quite a bit or very much to the screening question During the past seven days, did you feel fatigued: Not at all, a little bit, somewhat, quite a bit, very much? * Ability to walk without requiring assistance from another individual (use of cane or walker acceptable) * Normal organ and marrow function as defined below: * leukocytes \>3,000/mcL * absolute neutrophil count \>1,500/mcL * platelets \>100,000/mcL * total bilirubin within normal institutional limits * AST(SGOT)/ALT(SGPT) \<2.5 X institutional upper limit of normal * creatinine clearance \>30 mL/min * Ability to understand and the willingness to sign an IRB-approved informed consent document (either directly or via a legally authorized representative).
Exclusion criteria
* Active malignancy or on-going cancer treatment including oral anti-estrogen therapy, immunotherapy, biologic therapy. * Men receiving androgen deprivation therapy * Use of Coumadin or Warfarin (other blood thinners are acceptable) * Symptomatic congestive heart failure * Lung disease requiring oxygen * End stage renal disease requiring dialysis * Inability to swallow capsules * Chronic nausea or diarrhea defined by a frequency of ≥ once per week * Hemoglobin \<10 g/dl * Diagnosis of dementia * Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Known untreated hypothyroidism * Allergy to muscadine grapes or muscadine grape preparations
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Patient Reported Outcomes Measurement System (PROMIS) Fatigue 7a Questionnaire | At baseline and at 12 weeks | (PROMIS) Fatigue 7a will be used to assess fatigue. Using a mixed effects model with a constraint of a common baseline mean across treatment groups and an unstructured covariance matrix to model all fatigue measures over time, and use linear contrasts to estimate the difference in change and corresponding 90% confidence interval between the two groups. Item responses are rated on a five-point scale ranging from never to always and are summed for a total score and transformed to a T-score metric, which has a mean of 50 and a standard deviation of 10. Higher scores indicate more fatigue. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Short Physical Performance Battery (SPPB) | At 12 weeks | The Short Physical Performance Battery (SPPB) will be used to objectively assess lower extremity physical function. This validated measure comprises a short walk, repeated chair stands, and balance test. Each section is scored out of 4 points, so the highest total score for the SPPB is 12 points. Score range is 0-12. Poor (0-6), moderate 7-9) and good (10-12). Lower scores on the SPPB have been associated with increased risk of disability, hospitalization and worse survival among older adults with and without cancer. Investigators will estimate 95% confidence intervals for the differences between the two groups for the secondary outcomes at 12 weeks. |
| Short Form Minnesota Leisure Time Activity Questionnaire (MLTA) | At 12 weeks | This questionnaire will assess self-reported physical activity with participants answering yes/no questions in regards to physical activities done in the past two weeks and the frequency of those activities. Score is interpreted by calculating the total energy expenditure based on the frequency and duration of reported leisure activities, with higher scores indicating a greater level of physical activity; generally, scores are categorized as low (inactive), moderate (moderately active), and high (highly active). Investigators will estimate 95% confidence intervals for the differences between the two groups for the secondary outcomes at 12 weeks. |
| 6-Minute Walk Test | At 12 weeks | A 6-minute walk will be measured to assess physical fitness. The 6-minute walk is easy to administer in a clinical setting, accurately assesses submaximal exercise capacity, is an independent predictor of mortality and is correlated with peak V02 testing. The number of laps and distance walked on the final lap will be recorded. The total distance the participant walked will be entered onto the online database (1 lap = 30 meters distance). Investigators will estimate 95% confidence intervals for the differences between the two groups for the secondary outcomes at 12 weeks. |
| Pepper Assessment Tool for Disability (PAT-D) Questionnaire - Change From Baseline at 12 Weeks | At 12 weeks | Pepper Assessment Tool for Disability (PAT-D) will used to assess self-reported physical function. The (PAT-D) is a 19-item survey designed to assess domains of physical function in older adults which contains subscales on mobility, instrumental activities of daily living (IADLs), and basic activities of daily living (ADLs). Participant responses will best describe their ability to perform certain activities of daily living (On a scale of 1 to 5; 1 = usually did with no difficulty to 5 = unable to do. Minimum score of 19, max score of 95. A lower score indicates less difficulty with tasks and better function. Investigators will estimate 95% confidence intervals for the differences between the two groups for the secondary outcomes at 12 weeks reported as mean and standard error scores. |
| Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health Short Form (SF) - Quality of Life | At 12 weeks | The PROMIS Global Health Short Form (SF) is a 10-item questionnaire that will assess global quality of life including overall physical health, mental health, social health, pain, fatigue an overall perceived quality of life. Participants will respond to questions or statements with varied selections (excellent to poor; completely to not at all; never to always; and none to very severe). Scores above 50 are considered a better than average quality of life and scores below 50 are considered below average quality of life. Higher T-scores indicate better health, so scores around 50 are average, while scores below 40 suggest poor health warranting further assessment, and scores above 60 indicate excellent health. 50 indicates the population mean with a standard deviation of 10 Investigators will estimate 95% confidence intervals for the differences between the two groups for the secondary outcomes at 12 weeks. |
| Adherence - Pill Count | 12 weeks | Adherence will be measured by pill count at study completion. Investigators will estimate 95% confidence intervals for the differences between the two groups for the secondary outcomes at 12 weeks. |
| Fried Frailty Index | At 12 weeks | Frailty indexes will be assessed for differences between the two arms. The Fried frailty index is a scoring system that classifies people into three stages of frailty based on five criteria: weight loss, exhaustion, low physical activity, and slowness. Frailty index scores can be calculated by dividing the sum of the recoded values of the variables by the number of variables measured for a person. Corresponding scores are: Score of 0, non-frail; score of 1-2 pre-frail; score of 3-5 frail. Higher scores represent higher rates of frailty among participants. Investigators will estimate 95% confidence intervals for the differences between the two groups for the secondary outcomes at 12 weeks. |
| Longitudinal Aging Study Amsterdam (LASA) Sedentary Behavior Questionnaire | At 12 weeks | The questionnaire will be used to measure sedentary behavior for time spent during a 24 hour period for weekday and weekend various activities. The questionnaire consists of 10 items. The average time per 24 hours on each sedentary activity will be recorded in hours and/or minutes. Scores represent the self-reported average time an older adult spends engaged in sedentary activities (i.e., watching TV, reading, or sitting during a typical weekday and weekend day), with higher scores indicating a greater amount of time spent sedentary. Investigators will estimate 95% confidence intervals for the differences between the two groups for the secondary outcomes at 12 weeks. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Muscadine Grape Extract Arm Muscadine grape extract pill (12 week supply)
Muscadine grape extract: Four pills twice daily
Quality of Life Assessment: Ancillary studies
Questionnaires: Ancillary studies
Participant Feedback: Ancillary studies | 32 |
| Placebo Arm Placebo provided (12 week supply)
Placebo: Four pills twice daily.
Quality of Life Assessment: Ancillary studies
Questionnaires: Ancillary studies
Participant Feedback: Ancillary studies | 32 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo Arm | Total | Muscadine Grape Extract Arm |
|---|---|---|---|
| Age, Continuous | 75.8 Years STANDARD_DEVIATION 5.7 | 75.8 Years STANDARD_DEVIATION 5.5 | 75.8 Years STANDARD_DEVIATION 5.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 30 Participants | 60 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 4 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 28 Participants | 58 Participants | 30 Participants |
| Region of Enrollment United States | 32 participants | 64 participants | 32 participants |
| Sex: Female, Male Female | 27 Participants | 50 Participants | 23 Participants |
| Sex: Female, Male Male | 5 Participants | 14 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 0 / 32 |
| other Total, other adverse events | 29 / 32 | 28 / 32 |
| serious Total, serious adverse events | 0 / 32 | 1 / 32 |
Outcome results
Primary
Patient Reported Outcomes Measurement System (PROMIS) Fatigue 7a Questionnaire
(PROMIS) Fatigue 7a will be used to assess fatigue. Using a mixed effects model with a constraint of a common baseline mean across treatment groups and an unstructured covariance matrix to model all fatigue measures over time, and use linear contrasts to estimate the difference in change and corresponding 90% confidence interval between the two groups. Item responses are rated on a five-point scale ranging from never to always and are summed for a total score and transformed to a T-score metric, which has a mean of 50 and a standard deviation of 10. Higher scores indicate more fatigue.
Time frame: At baseline and at 12 weeks
Population: Not all participants reported data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Muscadine Grape Extract Arm | Patient Reported Outcomes Measurement System (PROMIS) Fatigue 7a Questionnaire | -6.6 score on a scale | Standard Error 1.1 |
| Placebo Arm | Patient Reported Outcomes Measurement System (PROMIS) Fatigue 7a Questionnaire | -5.4 score on a scale | Standard Error 2.2 |
90% CI: [-3.5, 1.1]
Secondary
6-Minute Walk Test
A 6-minute walk will be measured to assess physical fitness. The 6-minute walk is easy to administer in a clinical setting, accurately assesses submaximal exercise capacity, is an independent predictor of mortality and is correlated with peak V02 testing. The number of laps and distance walked on the final lap will be recorded. The total distance the participant walked will be entered onto the online database (1 lap = 30 meters distance). Investigators will estimate 95% confidence intervals for the differences between the two groups for the secondary outcomes at 12 weeks.
Time frame: At 12 weeks
Population: Not all participants reported data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Muscadine Grape Extract Arm | 6-Minute Walk Test | 369.8 meters | Standard Error 22.1 |
| Placebo Arm | 6-Minute Walk Test | 349.1 meters | Standard Error 14.4 |
95% CI: [-32.4, 73.8]
Secondary
Adherence - Pill Count
Adherence will be measured by pill count at study completion. Investigators will estimate 95% confidence intervals for the differences between the two groups for the secondary outcomes at 12 weeks.
Time frame: 12 weeks
Population: Not all participants reported data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Muscadine Grape Extract Arm | Adherence - Pill Count | 569.1 number of pills | Standard Error 35.4 |
| Placebo Arm | Adherence - Pill Count | 568.0 number of pills | Standard Error 35.8 |
95% CI: [-99.7, 101.9]
Secondary
Fried Frailty Index
Frailty indexes will be assessed for differences between the two arms. The Fried frailty index is a scoring system that classifies people into three stages of frailty based on five criteria: weight loss, exhaustion, low physical activity, and slowness. Frailty index scores can be calculated by dividing the sum of the recoded values of the variables by the number of variables measured for a person. Corresponding scores are: Score of 0, non-frail; score of 1-2 pre-frail; score of 3-5 frail. Higher scores represent higher rates of frailty among participants. Investigators will estimate 95% confidence intervals for the differences between the two groups for the secondary outcomes at 12 weeks.
Time frame: At 12 weeks
Population: Not all participants reported data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Muscadine Grape Extract Arm | Fried Frailty Index | 0.9 score on a scale | Standard Error 0.2 |
| Placebo Arm | Fried Frailty Index | 0.9 score on a scale | Standard Error 0.2 |
95% CI: [-0.5, 0.5]
Secondary
Longitudinal Aging Study Amsterdam (LASA) Sedentary Behavior Questionnaire
The questionnaire will be used to measure sedentary behavior for time spent during a 24 hour period for weekday and weekend various activities. The questionnaire consists of 10 items. The average time per 24 hours on each sedentary activity will be recorded in hours and/or minutes. Scores represent the self-reported average time an older adult spends engaged in sedentary activities (i.e., watching TV, reading, or sitting during a typical weekday and weekend day), with higher scores indicating a greater amount of time spent sedentary. Investigators will estimate 95% confidence intervals for the differences between the two groups for the secondary outcomes at 12 weeks.
Time frame: At 12 weeks
Population: Not all participants reported data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Muscadine Grape Extract Arm | Longitudinal Aging Study Amsterdam (LASA) Sedentary Behavior Questionnaire | 13.2 hours | Standard Error 1 |
| Placebo Arm | Longitudinal Aging Study Amsterdam (LASA) Sedentary Behavior Questionnaire | 12.7 hours | Standard Error 0.9 |
95% CI: [-2.2, 3.2]
Secondary
Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health Short Form (SF) - Quality of Life
The PROMIS Global Health Short Form (SF) is a 10-item questionnaire that will assess global quality of life including overall physical health, mental health, social health, pain, fatigue an overall perceived quality of life. Participants will respond to questions or statements with varied selections (excellent to poor; completely to not at all; never to always; and none to very severe). Scores above 50 are considered a better than average quality of life and scores below 50 are considered below average quality of life. Higher T-scores indicate better health, so scores around 50 are average, while scores below 40 suggest poor health warranting further assessment, and scores above 60 indicate excellent health. 50 indicates the population mean with a standard deviation of 10 Investigators will estimate 95% confidence intervals for the differences between the two groups for the secondary outcomes at 12 weeks.
Time frame: At 12 weeks
Population: Not all participants reported data for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Muscadine Grape Extract Arm | Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health Short Form (SF) - Quality of Life | Quality of Life - Self-rate health | 3.4 T score | Standard Error 0.1 |
| Muscadine Grape Extract Arm | Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health Short Form (SF) - Quality of Life | Quality of life - Ability to carry out social activities and roles | 3.9 T score | Standard Error 0.2 |
| Muscadine Grape Extract Arm | Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health Short Form (SF) - Quality of Life | Physical health (t score) | 47.2 T score | Standard Error 1.2 |
| Muscadine Grape Extract Arm | Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health Short Form (SF) - Quality of Life | Mental health (t score) | 50.6 T score | Standard Error 1.5 |
| Placebo Arm | Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health Short Form (SF) - Quality of Life | Mental health (t score) | 52.0 T score | Standard Error 1.3 |
| Placebo Arm | Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health Short Form (SF) - Quality of Life | Quality of Life - Self-rate health | 3.2 T score | Standard Error 0.1 |
| Placebo Arm | Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health Short Form (SF) - Quality of Life | Physical health (t score) | 46.3 T score | Standard Error 1.3 |
| Placebo Arm | Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health Short Form (SF) - Quality of Life | Quality of life - Ability to carry out social activities and roles | 3.7 T score | Standard Error 0.2 |
Comparison: Quality of Life - Self-rate health95% CI: [-0.2, 0.7]
95% CI: [-0.3, 0.6]
Comparison: Physical health (t score)95% CI: [-2.7, 4.5]
Comparison: Global Mental health (t score95% CI: [-5.4, 2.5]
Secondary
Pepper Assessment Tool for Disability (PAT-D) Questionnaire - Change From Baseline at 12 Weeks
Pepper Assessment Tool for Disability (PAT-D) will used to assess self-reported physical function. The (PAT-D) is a 19-item survey designed to assess domains of physical function in older adults which contains subscales on mobility, instrumental activities of daily living (IADLs), and basic activities of daily living (ADLs). Participant responses will best describe their ability to perform certain activities of daily living (On a scale of 1 to 5; 1 = usually did with no difficulty to 5 = unable to do. Minimum score of 19, max score of 95. A lower score indicates less difficulty with tasks and better function. Investigators will estimate 95% confidence intervals for the differences between the two groups for the secondary outcomes at 12 weeks reported as mean and standard error scores.
Time frame: At 12 weeks
Population: Not all participants reported data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Muscadine Grape Extract Arm | Pepper Assessment Tool for Disability (PAT-D) Questionnaire - Change From Baseline at 12 Weeks | 1.4 mean score on a scale | Standard Error 0.1 |
| Placebo Arm | Pepper Assessment Tool for Disability (PAT-D) Questionnaire - Change From Baseline at 12 Weeks | 1.6 mean score on a scale | Standard Error 0.1 |
95% CI: [-0.5, 0.1]
Secondary
Short Form Minnesota Leisure Time Activity Questionnaire (MLTA)
This questionnaire will assess self-reported physical activity with participants answering yes/no questions in regards to physical activities done in the past two weeks and the frequency of those activities. Score is interpreted by calculating the total energy expenditure based on the frequency and duration of reported leisure activities, with higher scores indicating a greater level of physical activity; generally, scores are categorized as low (inactive), moderate (moderately active), and high (highly active). Investigators will estimate 95% confidence intervals for the differences between the two groups for the secondary outcomes at 12 weeks.
Time frame: At 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Muscadine Grape Extract Arm | Short Form Minnesota Leisure Time Activity Questionnaire (MLTA) | 3218 kcal/week | Standard Error 517 |
| Placebo Arm | Short Form Minnesota Leisure Time Activity Questionnaire (MLTA) | 4192 kcal/week | Standard Error 1141 |
95% CI: [-3500, 1553]
Secondary
Short Physical Performance Battery (SPPB)
The Short Physical Performance Battery (SPPB) will be used to objectively assess lower extremity physical function. This validated measure comprises a short walk, repeated chair stands, and balance test. Each section is scored out of 4 points, so the highest total score for the SPPB is 12 points. Score range is 0-12. Poor (0-6), moderate 7-9) and good (10-12). Lower scores on the SPPB have been associated with increased risk of disability, hospitalization and worse survival among older adults with and without cancer. Investigators will estimate 95% confidence intervals for the differences between the two groups for the secondary outcomes at 12 weeks.
Time frame: At 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Muscadine Grape Extract Arm | Short Physical Performance Battery (SPPB) | 9.8 points | Standard Error 0.5 |
| Placebo Arm | Short Physical Performance Battery (SPPB) | 9.2 points | Standard Error 0.5 |
95% CI: [-0.7, 2]