Prostate Cancer
Conditions
Keywords
Prostate Cancer, Men, Androgen Deprivation Therapy, Elderly, Geriatric, Nutritional supplementation
Brief summary
This is a study of HMB plus amino acids in older men with prostate cancer starting androgen deprivation therapy (ADT). The investigators hypothesize that the use of this nutritional supplementation will decrease the loss of muscle mass and strength that occurs when men start ADT.
Detailed description
It is well established that older patients experience age-related loss of muscle mass and function (sarcopenia), presumably due to an imbalance of protein synthesis versus protein breakdown. In addition, studies have shown that men who start on ADT experience increased muscle protein breakdown and decreased synthesis. β-hydroxy-β-methylbutyrate (HMB), a leucine metabolite, has been shown to slow protein breakdown. When HMB is given with arginine and lysine (which support protein synthesis) in randomized trials, researchers have shown that elderly men and women who receive this nutritional supplementation experience improvement in fat-free mass, strength, functionality and protein synthesis when compared with controls. In addition, patients with advanced cancer who experienced weight loss of at least 5% have also been shown to benefit from HMB, with supplementation resulting in a significant increase of fat-free mass when compared to controls. Thus, it seems reasonable that older men with prostate cancer starting on ADT who experience lean muscle loss as a result of aging and ADT, may achieve some benefit from supplementation with HMB as well. Use of HMB in men with prostate cancer has not been reported.
Interventions
DRUGStandard of care ADT + (HMB + arginine + glutamine)
1 packet of HMB+arginine+glutamine contains 1.5 g of the amino acid metabolite HMB + 7 g arginine and 7 g glutamine. Take one packet twice daily for 3 months
OTHERStandard of care ADT
Patient will receive standard of care androgen deprivation therapy (ADT) alone
Sponsors
Medical College of Wisconsin
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically confirmed adenocarcinoma of the prostate 2. Age 60 years or older 3. Patients with asymptomatic or minimally symptomatic prostate cancer for which they are about to start androgen deprivation therapy (ADT) per provider recommendation * Asymptomatic or minimally symptomatic (as judged by treating physician) metastases allowed * Men receiving ADT for localized prostate cancer are allowed 4. Patient able to give informed consent.
Exclusion criteria
1. Patient already on ADT 2. Patients who are visiting clinic for a second opinion only 3. Patients with a diagnosis of dementia 4. Patients with a diagnosis of a neuromuscular disorder (i.e. multiple sclerosis)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Body Composition (Lean Body Mass) | Baseline, 3 months | This measure will be the change of lean body mass from baseline reported in kilograms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline of Dorsiflexor Muscle Size in mm^2. | Baseline and 3 months | Cross-sectional area of the dorsiflexor muscle will be measured in mm\^2 using magnetic resonance imaging. The dorsiflexor muscles at the front of the leg are responsible for lifting the ball of the foot with the heel in contact with the ground. One dorsiflexor muscle in one leg was analyzed per participant. |
| Change From Baseline in Strength of the Dorsiflexor Muscle in Kilograms. | Baseline and 3 months | Dorsiflexor muscle strength in kilograms will be measured with a custom lower leg ergometer. The dorsiflexor muscles at the front of the leg are responsible for lifting the ball of the foot with the heel in contact with the ground. |
| Physical Performance Measured Using the Short Physical Performance Battery (SPPB) | Baseline and 3 months | The SPPB uses Likert-style ratings for balance, walking speed, and standing test (Guralnik, 2000). Balance metric is the ability to hold three standing positions (feet side-by-side; side of the heel of one foot touching the big toe of the other foot; heel of one foot in front of and touching the toes of the other) up to 10 seconds. Inability to hold a position scores '0'. The sum of scores is the Balance Score. Scoring range is 0-4. Higher scores indicate better balance. Walking metric is time to walk 8 feet. Faster times score more points. Inability to complete the walk scores '0'. The score range is 0-4. Higher scores indicate better mobility. The Standing Test. The subject is asked to stand and sit five times as quickly as possible. Inability to complete five repetitions scores '0'. Shorter times score more points. Scoring range is 0-4. Higher scores indicate better mobility. Overall score is the sum of the scores ranging 0 to 12. Higher scores indicate better performance. |
| Change From Baseline in the Number of Fall Events | Baseline, 3 months | This measure will be the change in the number of reported falls from baseline (defined as the 3 months preceding the baseline visit), and the 3 month period beginning after the baseline visit and continuing through 3 months of therapy. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Standard of Care ADT + (HMB + AG) Standard of care androgen deprivation therapy plus the nutritional supplement HMB + arginine + glutamine (AG)
Standard of care ADT + (HMB + arginine + glutamine): 1 packet of HMB+arginine+glutamine contains 1.5 g of the amino acid metabolite HMB + 7 g arginine and 7 g glutamine.
Take one packet twice daily for 3 months | 24 |
| Standard of Care ADT Standard of care androgen deprivation therapy
Standard of care ADT: Patient will receive standard of care androgen deprivation therapy (ADT) alone | 24 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 0 |
Baseline characteristics
| Characteristic | Standard of Care ADT + (HMB + AG) | Standard of Care ADT | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 21 Participants | 14 Participants | 35 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 10 Participants | 13 Participants |
| Age, Continuous | 70.6 years STANDARD_DEVIATION 5.6 | 67.4 years STANDARD_DEVIATION 5.1 | 69.0 years STANDARD_DEVIATION 5.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants | 24 Participants | 47 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 | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 24 Participants | 22 Participants | 46 Participants |
| Region of Enrollment United States | 24 participants | 24 participants | 48 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 24 Participants | 24 Participants | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 24 | 0 / 24 |
| other Total, other adverse events | 8 / 24 | 7 / 24 |
| serious Total, serious adverse events | 1 / 24 | 2 / 24 |
Outcome results
Primary
Change From Baseline in Body Composition (Lean Body Mass)
This measure will be the change of lean body mass from baseline reported in kilograms.
Time frame: Baseline, 3 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care ADT + (HMB + AG) | Change From Baseline in Body Composition (Lean Body Mass) | Baseline | 54.93 Kilogram | Standard Deviation 8.66 |
| Standard of Care ADT + (HMB + AG) | Change From Baseline in Body Composition (Lean Body Mass) | Change from Baseline | -1.27 Kilogram | Standard Deviation 1.42 |
| Standard of Care ADT | Change From Baseline in Body Composition (Lean Body Mass) | Baseline | 57.58 Kilogram | Standard Deviation 7.39 |
| Standard of Care ADT | Change From Baseline in Body Composition (Lean Body Mass) | Change from Baseline | -0.60 Kilogram | Standard Deviation 2.22 |
p-value: 0.1497t-test, 1 sided
Secondary
Change From Baseline in Strength of the Dorsiflexor Muscle in Kilograms.
Dorsiflexor muscle strength in kilograms will be measured with a custom lower leg ergometer. The dorsiflexor muscles at the front of the leg are responsible for lifting the ball of the foot with the heel in contact with the ground.
Time frame: Baseline and 3 months
Population: Due to unavailability of equipment, only 5 subjects in the HMB+AG group and 10 subjects in the standard ADT group completed both baseline and 3 month follo-up visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care ADT + (HMB + AG) | Change From Baseline in Strength of the Dorsiflexor Muscle in Kilograms. | Baseline | 17.2 kilogram | Standard Deviation 3.1 |
| Standard of Care ADT + (HMB + AG) | Change From Baseline in Strength of the Dorsiflexor Muscle in Kilograms. | Change at 3 months | -1.0 kilogram | Standard Deviation 5.3 |
| Standard of Care ADT | Change From Baseline in Strength of the Dorsiflexor Muscle in Kilograms. | Baseline | 18.0 kilogram | Standard Deviation 3 |
| Standard of Care ADT | Change From Baseline in Strength of the Dorsiflexor Muscle in Kilograms. | Change at 3 months | 1.0 kilogram | Standard Deviation 2 |
p-value: 0.75t-test, 2 sided
Secondary
Change From Baseline in the Number of Fall Events
This measure will be the change in the number of reported falls from baseline (defined as the 3 months preceding the baseline visit), and the 3 month period beginning after the baseline visit and continuing through 3 months of therapy.
Time frame: Baseline, 3 months
Population: Three subjects in the HMB+AG group did not report the number of falls at the 3-month follow-up.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Standard of Care ADT + (HMB + AG) | Change From Baseline in the Number of Fall Events | Baseline | 1 Falls |
| Standard of Care ADT + (HMB + AG) | Change From Baseline in the Number of Fall Events | Change at 3 months | -1 Falls |
| Standard of Care ADT | Change From Baseline in the Number of Fall Events | Baseline | 0 Falls |
| Standard of Care ADT | Change From Baseline in the Number of Fall Events | Change at 3 months | 0 Falls |
p-value: 1Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline of Dorsiflexor Muscle Size in mm^2.
Cross-sectional area of the dorsiflexor muscle will be measured in mm\^2 using magnetic resonance imaging. The dorsiflexor muscles at the front of the leg are responsible for lifting the ball of the foot with the heel in contact with the ground. One dorsiflexor muscle in one leg was analyzed per participant.
Time frame: Baseline and 3 months
Population: Due to unavailability of equipment, only 5 subjects in the HMB+AG group and 8 subjects in the standard ADT therapy group completed both baseline and 3 months follow-up measurements.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care ADT + (HMB + AG) | Change From Baseline of Dorsiflexor Muscle Size in mm^2. | Baseline | 1378 mm^2 | Standard Deviation 322 |
| Standard of Care ADT + (HMB + AG) | Change From Baseline of Dorsiflexor Muscle Size in mm^2. | Change at 3 months | -36 mm^2 | Standard Deviation 37 |
| Standard of Care ADT | Change From Baseline of Dorsiflexor Muscle Size in mm^2. | Baseline | 1348 mm^2 | Standard Deviation 177 |
| Standard of Care ADT | Change From Baseline of Dorsiflexor Muscle Size in mm^2. | Change at 3 months | 30 mm^2 | Standard Deviation 164 |
p-value: 0.17t-test, 2 sided
Secondary
Physical Performance Measured Using the Short Physical Performance Battery (SPPB)
The SPPB uses Likert-style ratings for balance, walking speed, and standing test (Guralnik, 2000). Balance metric is the ability to hold three standing positions (feet side-by-side; side of the heel of one foot touching the big toe of the other foot; heel of one foot in front of and touching the toes of the other) up to 10 seconds. Inability to hold a position scores '0'. The sum of scores is the Balance Score. Scoring range is 0-4. Higher scores indicate better balance. Walking metric is time to walk 8 feet. Faster times score more points. Inability to complete the walk scores '0'. The score range is 0-4. Higher scores indicate better mobility. The Standing Test. The subject is asked to stand and sit five times as quickly as possible. Inability to complete five repetitions scores '0'. Shorter times score more points. Scoring range is 0-4. Higher scores indicate better mobility. Overall score is the sum of the scores ranging 0 to 12. Higher scores indicate better performance.
Time frame: Baseline and 3 months
Population: Four subjects in the HMB+AG group and one subject in the standard ADT group did not complete the SPPB test at the 3-month follow-up.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care ADT + (HMB + AG) | Physical Performance Measured Using the Short Physical Performance Battery (SPPB) | Baseline | 10.6 score on a scale | Standard Deviation 1.6 |
| Standard of Care ADT + (HMB + AG) | Physical Performance Measured Using the Short Physical Performance Battery (SPPB) | 3 months | 11.1 score on a scale | Standard Deviation 1.1 |
| Standard of Care ADT | Physical Performance Measured Using the Short Physical Performance Battery (SPPB) | Baseline | 10.7 score on a scale | Standard Deviation 1.7 |
| Standard of Care ADT | Physical Performance Measured Using the Short Physical Performance Battery (SPPB) | 3 months | 11.0 score on a scale | Standard Deviation 1.2 |
p-value: 0.925Wilcoxon (Mann-Whitney)