Optimizing Protein Intake in Older Americans With Mobility Limitations (OPTIMen)
Primary Purpose
Mobility Limitation
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Testosterone enanthate
Testosterone enanthate
Sponsored by
About this trial
This is an interventional treatment trial for Mobility Limitation focused on measuring Mobility Limitation, Low Protein Intake, Older Men, Testosterone
Eligibility Criteria
Inclusion Criteria:
- Community-dwelling men 65 years of age or older
- A score of 3-10 on the short physical performance battery (SPPB)
- Daily protein intake less than the recommended daily allowance of 0.83 g/kg/day (from 3 24-hour food recalls)
- Able to give informed consent
Exclusion Criteria:
- History of prostate or breast cancer
- American Urological Association [AUA] symptom index score of >19
- Prostate specific antigen (PSA) >4 ng/ml in White men or >3 ng/ml in Black men
- Prostate specific antigen (PSA) > 4 ng/ml in non-Black men or >3 ng/ml in Black men. These subjects may be enrolled if they have a negative transrectal biopsy within the past year.
- Myocardial infarction or stroke within the last 6 months
- Uncontrolled congestive heart failure, based on the study physician's evaluation
- Serum creatinine > 2.0 mg/dL; men on any kind of dialysis will be excluded.
- History of celiac disease, Crohn's disease, or ulcerative colitis
- History of any malignancy requiring treatment within the previous 2 years, except non-melanic skin cancers. Men with cancers who have not required active treatment within the past two years and who have not had disease recurrence within the past two years may be enrolled at the discretion of the study physician.
- Neuromuscular diseases: motor neuron diseases, multiple sclerosis, adult muscular dystrophies, and myasthenia gravis
- History of stroke with residual limb weakness that affected the individual's ability to walk; subjects with history of stroke who do not have residual limb weakness may be enrolled.
- Schizophrenia, bipolar disorder, or untreated diagnosed depression. Subjects with unipolar depression who are on an antidepressant medication are eligible.
- TSH levels <0.4 or >5 mlU/L
- Systolic blood pressure (BP) >160 or diastolic BP >100 mm Hg (average of 2 measurements taken at Visit 1)
- Hemoglobin A1c >8.0% or taking insulin. Men with diabetes mellitus whose A1C is less than 8.0% or who are not taking insulin will be eligible.
- Mini-Mental Status Exam [MMSE] <24
- Body mass index (BMI) less than 20 or greater than 40 kg/m2
- Not willing to eat all of the following: red meat, eggs, poultry, fish and shellfish
- Allergy to sesame, peanuts, soy, gluten or shellfish
- Current alcohol use >21 drinks/week based on self-report
- Confinement to a wheelchair
- Use of anabolic therapies (Testosterone, DHEA, androstenedione, rhGH) within the past year
- Current use of levodopa or anticoagulants
- Current enrollment in a structured weight management program or participation in any weight intervention studies in the last 90 days
- Serum ALT and AST greater than 3 x upper limit of normal
- Hematocrit < 30% or >48%
- Subject is not able to eat 3 frozen study meals per day for 6 months
- Subject is unwilling to stop current nutritional supplements
- Progressive intensive resistance training within 12 weeks of screening
- Non-compliant with run-in diet and/or supplement
Sites / Locations
- Brigham and Women's Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
No Intervention
No Intervention
Other
Other
Arm Label
Placebo/Low Protein
Placebo/High Protein
Testosterone/Low Protein
Testosterone/High Protein
Arm Description
Placebo injections weekly; 0.8 g/kg/day protein
Placebo injections weekly; 1.3 g/kg/day protein
Testosterone enanthate 100 mg intramuscularly weekly; 0.8 g/kg/day protein
Testosterone enanthate 100 mg intramuscularly weekly; 1.3 g/kg/day protein
Outcomes
Primary Outcome Measures
Change in Lean Body Mass as Measured by Dual Energy X-ray Absorptiometry (DXA)
Primary outcome is change in lean body mass, measured by dual energy X-ray absorptiometry (DXA)
Secondary Outcome Measures
Change of Maximal Voluntary Strength
Tests of Muscle Performance: (1) Maximal voluntary strength measured by 1-repetition maximum method in leg press; (2) Maximal voluntary strength in chest press; this exercise was chosen because it involves the large muscle groups of the upper extremities.
Change of Leg Press Power
Muscle Performance measured using Power of hip and knee extension by Bassey's leg rig.
Change of 6-minute Walking Distance
Tests of Physical Function and Task-Specific Performance measured by 6-min walking distance
Change of Stair Climbing Tests
Tests of Physical Function and Task-Specific Performance measured by Stair-climbing power +/- 20% load carry. Physical Function was evaluated using two tests of stair climb power using an indoor 12-step staircase. One test consisted of ascending the 12-steps as rapidly as possible without running (unloaded stair climb) while the second test required participants to carry a load equivalent to 20% of their baseline body weight evenly distributed in two canvas tote bags (loaded stair climb). Time to ascend the stairs was measured electronically with a digital clock and switch mats placed at the base of the steps and on the 12th step. Power in watts is calculated by the following: [body weight (kilograms) * distance (meters)/ (time/60)] /6.12.
Change of 50-meter Loaded Walking Test
Tests of Physical Function and Task-Specific Performance measured by 50-meter timed walk + 20% load carry. Physical Function was evaluated using test of 50-meter loaded walking speed. The test required participants to carry a load equivalent to 20% of their baseline body weight evenly distributed in two canvas tote bags. Time was measured electronically with a digital clock. Speed in meters per second is calculated by the following: 50/time.
Change of Self-reported Physical Function Domain of Short Form Health Survey (SF-36)
36-Item Short Form Health Survey (SF-36) is a set of generic, coherent, and easily administered quality-of-life measures. Physical function domain of the Medical Outcomes Study Short Form-36 (SF-36) contains 10 items with the score range of 0-100. Higher score yields better performance.
Change of Psychological Well Being Index (PGWBI)
The PGWBI is a 22-item health-related Quality of Life (HRQoL) questionnaire developed in US which produces a self-perceived evaluation of psychological well-being expressed by a summary score. The 22 items are grouped in 6 dimensions. A global score is computed as the sum of all items with range of 0-110. A higher score yields better performance.
Change of Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale
The FACIT Fatigue Scale is a 13-item questionnaire that measures an individual's level of fatigue during their usual daily activities over the past week. The level of fatigue is measured on a four point scale (4 = not at all fatigued to 0 = very much fatigued). Score ranges 0-52. The higher the score, the better the quality of life.
Change of Derogatis Affective Balance Scale (DABS)
The Derogatis Affects Balance Scale (DABS) is a multidimensional self-report mood and affects inventory comprised of 40 adjective-items using a 5-point Likert style scale. The DABS global scores consist of the Positive Total score (PTOT), Negative Total score (NTOT), where The Positive Affects Total (PTOT) is defined as the sum of all scores on the four positive affects dimensions of joy, contentment, vigor and affection, ranging 0-80. Similarly, the Negative Affects Total (NTOT) is represented as the sum of scores on the four negative dimensions of anxiety, depression, guilt and hostility, ranging 0-80. The Affects Expressiveness Index (AEI) is defined as the sum total of PTOT and NTOT, ranging 0-160. Higher score yields stronger affective intensity.
Full Information
NCT ID
NCT01275365
First Posted
January 11, 2011
Last Updated
July 27, 2021
Sponsor
Brigham and Women's Hospital
Collaborators
National Institute on Aging (NIA)
1. Study Identification
Unique Protocol Identification Number
NCT01275365
Brief Title
Optimizing Protein Intake in Older Americans With Mobility Limitations
Acronym
OPTIMen
Official Title
Optimizing Protein Intake in Older Americans With Mobility Limitations
Study Type
Interventional
2. Study Status
Record Verification Date
July 2021
Overall Recruitment Status
Completed
Study Start Date
May 2011 (undefined)
Primary Completion Date
January 19, 2017 (Actual)
Study Completion Date
January 19, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Brigham and Women's Hospital
Collaborators
National Institute on Aging (NIA)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This will be a randomized, placebo-controlled, parallel group, double blind, clinical trial in community dwelling, older men, 65 years of age or older, who have mobility limitation and low protein intake. The study will have a 2 X 2 factorial design, which will allow us to investigate the effects of dietary protein intake and testosterone separately and together.
Detailed Description
The recommended dietary allowance (RDA) for protein, set at 0.8 grams/kg/day for adult men and women, has engendered debate and many experts advocate protein intakes substantially above the RDA to help maintain muscle anabolism in older individuals. It is not known whether increasing protein intake in older Americans, whose current intake is below the RDA, increases skeletal muscle mass, muscle performance and physical function.
Our first aim is to determine whether administration of 1.3 g/kg/day of protein, compared to the RDA (0.8 g/kg/day), will result in greater improvements in lean body mass, maximal voluntary muscle strength and power, and self-reported and performance-based measures of physical function in older men. Our second aim is to determine whether the gains in lean body mass, maximal voluntary strength and self-reported and performance-based measures of physical function during testosterone administration are greater with 1.3 g protein than with the RDA in older men on a eucaloric diet.
We will conduct a randomized, placebo-controlled, double-blind trial using a 2 X 2 factorial design. Community dwelling men, 65 years or older, who have self-reported mobility limitation, a daily protein intake of <0.8 g/kg/day and no contraindications for testosterone therapy, will be randomly assigned to one of four groups: placebo injections plus protein 0.8 g/kg/day; placebo injections plus protein 1.3 g/kg/day; testosterone enanthate 100 mg weekly plus protein 0.8 g/kg/day; testosterone enanthate 100 mg weekly plus protein 1.3 g/kg/day. Treatment duration will be 6 months. The primary outcome is change in lean body mass from baseline to 6 months, measured by dual energy X-ray absorptiometry. Secondary outcomes include change in maximal voluntary strength in leg and chest press exercises, leg power, self-reported (physical function domain of SF-36) and performance-based measures of physical function (6-min walking distance and speed, stair climbing power, and load carrying), fatigue, well-being and affectivity balance. Safety measures include urinary calcium excretion, hematocrit, prostate specific antigen (PSA) and prostate examination.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mobility Limitation
Keywords
Mobility Limitation, Low Protein Intake, Older Men, Testosterone
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Factorial Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
92 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo/Low Protein
Arm Type
No Intervention
Arm Description
Placebo injections weekly; 0.8 g/kg/day protein
Arm Title
Placebo/High Protein
Arm Type
No Intervention
Arm Description
Placebo injections weekly; 1.3 g/kg/day protein
Arm Title
Testosterone/Low Protein
Arm Type
Other
Arm Description
Testosterone enanthate 100 mg intramuscularly weekly; 0.8 g/kg/day protein
Arm Title
Testosterone/High Protein
Arm Type
Other
Arm Description
Testosterone enanthate 100 mg intramuscularly weekly; 1.3 g/kg/day protein
Intervention Type
Drug
Intervention Name(s)
Testosterone enanthate
Intervention Description
Testosterone enanthate 100 mg intramuscularly weekly
Intervention Type
Drug
Intervention Name(s)
Testosterone enanthate
Intervention Description
Testosterone enanthate 100 mg intramuscularly weekly
Primary Outcome Measure Information:
Title
Change in Lean Body Mass as Measured by Dual Energy X-ray Absorptiometry (DXA)
Description
Primary outcome is change in lean body mass, measured by dual energy X-ray absorptiometry (DXA)
Time Frame
6 months from baseline
Secondary Outcome Measure Information:
Title
Change of Maximal Voluntary Strength
Description
Tests of Muscle Performance: (1) Maximal voluntary strength measured by 1-repetition maximum method in leg press; (2) Maximal voluntary strength in chest press; this exercise was chosen because it involves the large muscle groups of the upper extremities.
Time Frame
6 months from baseline
Title
Change of Leg Press Power
Description
Muscle Performance measured using Power of hip and knee extension by Bassey's leg rig.
Time Frame
6 months from baseline
Title
Change of 6-minute Walking Distance
Description
Tests of Physical Function and Task-Specific Performance measured by 6-min walking distance
Time Frame
6 months from baseline
Title
Change of Stair Climbing Tests
Description
Tests of Physical Function and Task-Specific Performance measured by Stair-climbing power +/- 20% load carry. Physical Function was evaluated using two tests of stair climb power using an indoor 12-step staircase. One test consisted of ascending the 12-steps as rapidly as possible without running (unloaded stair climb) while the second test required participants to carry a load equivalent to 20% of their baseline body weight evenly distributed in two canvas tote bags (loaded stair climb). Time to ascend the stairs was measured electronically with a digital clock and switch mats placed at the base of the steps and on the 12th step. Power in watts is calculated by the following: [body weight (kilograms) * distance (meters)/ (time/60)] /6.12.
Time Frame
6 months from baseline
Title
Change of 50-meter Loaded Walking Test
Description
Tests of Physical Function and Task-Specific Performance measured by 50-meter timed walk + 20% load carry. Physical Function was evaluated using test of 50-meter loaded walking speed. The test required participants to carry a load equivalent to 20% of their baseline body weight evenly distributed in two canvas tote bags. Time was measured electronically with a digital clock. Speed in meters per second is calculated by the following: 50/time.
Time Frame
6 months from baseline
Title
Change of Self-reported Physical Function Domain of Short Form Health Survey (SF-36)
Description
36-Item Short Form Health Survey (SF-36) is a set of generic, coherent, and easily administered quality-of-life measures. Physical function domain of the Medical Outcomes Study Short Form-36 (SF-36) contains 10 items with the score range of 0-100. Higher score yields better performance.
Time Frame
6 months from baseline
Title
Change of Psychological Well Being Index (PGWBI)
Description
The PGWBI is a 22-item health-related Quality of Life (HRQoL) questionnaire developed in US which produces a self-perceived evaluation of psychological well-being expressed by a summary score. The 22 items are grouped in 6 dimensions. A global score is computed as the sum of all items with range of 0-110. A higher score yields better performance.
Time Frame
6 months from baseline
Title
Change of Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale
Description
The FACIT Fatigue Scale is a 13-item questionnaire that measures an individual's level of fatigue during their usual daily activities over the past week. The level of fatigue is measured on a four point scale (4 = not at all fatigued to 0 = very much fatigued). Score ranges 0-52. The higher the score, the better the quality of life.
Time Frame
6 months from baseline
Title
Change of Derogatis Affective Balance Scale (DABS)
Description
The Derogatis Affects Balance Scale (DABS) is a multidimensional self-report mood and affects inventory comprised of 40 adjective-items using a 5-point Likert style scale. The DABS global scores consist of the Positive Total score (PTOT), Negative Total score (NTOT), where The Positive Affects Total (PTOT) is defined as the sum of all scores on the four positive affects dimensions of joy, contentment, vigor and affection, ranging 0-80. Similarly, the Negative Affects Total (NTOT) is represented as the sum of scores on the four negative dimensions of anxiety, depression, guilt and hostility, ranging 0-80. The Affects Expressiveness Index (AEI) is defined as the sum total of PTOT and NTOT, ranging 0-160. Higher score yields stronger affective intensity.
Time Frame
6 months from baseline
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Community-dwelling men 65 years of age or older
A score of 3-10 on the short physical performance battery (SPPB)
Daily protein intake less than the recommended daily allowance of 0.83 g/kg/day (from 3 24-hour food recalls)
Able to give informed consent
Exclusion Criteria:
History of prostate or breast cancer
American Urological Association [AUA] symptom index score of >19
Prostate specific antigen (PSA) >4 ng/ml in White men or >3 ng/ml in Black men
Prostate specific antigen (PSA) > 4 ng/ml in non-Black men or >3 ng/ml in Black men. These subjects may be enrolled if they have a negative transrectal biopsy within the past year.
Myocardial infarction or stroke within the last 6 months
Uncontrolled congestive heart failure, based on the study physician's evaluation
Serum creatinine > 2.0 mg/dL; men on any kind of dialysis will be excluded.
History of celiac disease, Crohn's disease, or ulcerative colitis
History of any malignancy requiring treatment within the previous 2 years, except non-melanic skin cancers. Men with cancers who have not required active treatment within the past two years and who have not had disease recurrence within the past two years may be enrolled at the discretion of the study physician.
Neuromuscular diseases: motor neuron diseases, multiple sclerosis, adult muscular dystrophies, and myasthenia gravis
History of stroke with residual limb weakness that affected the individual's ability to walk; subjects with history of stroke who do not have residual limb weakness may be enrolled.
Schizophrenia, bipolar disorder, or untreated diagnosed depression. Subjects with unipolar depression who are on an antidepressant medication are eligible.
TSH levels <0.4 or >5 mlU/L
Systolic blood pressure (BP) >160 or diastolic BP >100 mm Hg (average of 2 measurements taken at Visit 1)
Hemoglobin A1c >8.0% or taking insulin. Men with diabetes mellitus whose A1C is less than 8.0% or who are not taking insulin will be eligible.
Mini-Mental Status Exam [MMSE] <24
Body mass index (BMI) less than 20 or greater than 40 kg/m2
Not willing to eat all of the following: red meat, eggs, poultry, fish and shellfish
Allergy to sesame, peanuts, soy, gluten or shellfish
Current alcohol use >21 drinks/week based on self-report
Confinement to a wheelchair
Use of anabolic therapies (Testosterone, DHEA, androstenedione, rhGH) within the past year
Current use of levodopa or anticoagulants
Current enrollment in a structured weight management program or participation in any weight intervention studies in the last 90 days
Serum ALT and AST greater than 3 x upper limit of normal
Hematocrit < 30% or >48%
Subject is not able to eat 3 frozen study meals per day for 6 months
Subject is unwilling to stop current nutritional supplements
Progressive intensive resistance training within 12 weeks of screening
Non-compliant with run-in diet and/or supplement
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shalender Bhasin, MD
Organizational Affiliation
Brigham and Women's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
33417663
Citation
Huang G, Pencina K, Li Z, Apovian CM, Travison TG, Storer TW, Gagliano-Juca T, Basaria S, Bhasin S. Effect of Protein Intake on Visceral Abdominal Fat and Metabolic Biomarkers in Older Men With Functional Limitations: Results From a Randomized Clinical Trial. J Gerontol A Biol Sci Med Sci. 2021 May 22;76(6):1084-1089. doi: 10.1093/gerona/glab007.
Results Reference
derived
PubMed Identifier
30932132
Citation
Krok-Schoen JL, Archdeacon Price A, Luo M, Kelly OJ, Taylor CA. Low Dietary Protein Intakes and Associated Dietary Patterns and Functional Limitations in an Aging Population: A NHANES analysis. J Nutr Health Aging. 2019;23(4):338-347. doi: 10.1007/s12603-019-1174-1.
Results Reference
derived
PubMed Identifier
29532075
Citation
Bhasin S, Apovian CM, Travison TG, Pencina K, Moore LL, Huang G, Campbell WW, Li Z, Howland AS, Chen R, Knapp PE, Singer MR, Shah M, Secinaro K, Eder RV, Hally K, Schram H, Bearup R, Beleva YM, McCarthy AC, Woodbury E, McKinnon J, Fleck G, Storer TW, Basaria S. Effect of Protein Intake on Lean Body Mass in Functionally Limited Older Men: A Randomized Clinical Trial. JAMA Intern Med. 2018 Apr 1;178(4):530-541. doi: 10.1001/jamainternmed.2018.0008.
Results Reference
derived
PubMed Identifier
29188864
Citation
Apovian CM, Singer MR, Campbell WW, Bhasin S, McCarthy AC, Shah M, Basaria S, Moore LL. Development of a Novel Six-Month Nutrition Intervention for a Randomized Trial in Older Men with Mobility Limitations. J Nutr Health Aging. 2017;21(10):1081-1088. doi: 10.1007/s12603-017-0990-4.
Results Reference
derived
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Optimizing Protein Intake in Older Americans With Mobility Limitations
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