Optimizing Protein Intake in Older Americans With Mobility Limitations

Phase 3

Completed

Conditions: Mobility Limitation

Interventions: Drug: Testosterone enanthate

Registration Number: NCT01275365

Lead Sponsor: Brigham and Women's Hospital

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 92

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Testosterone/Low Protein	Testosterone enanthate	Testosterone enanthate 100 mg intramuscularly weekly; 0.8 g/kg/day protein
Testosterone/High Protein	Testosterone enanthate	Testosterone enanthate 100 mg intramuscularly weekly; 1.3 g/kg/day protein

Primary Outcome Measures

Name	Time	Method
Change in Lean Body Mass as Measured by Dual Energy X-ray Absorptiometry (DXA)	6 months from baseline	Primary outcome is change in lean body mass, measured by dual energy X-ray absorptiometry (DXA)

Secondary Outcome Measures

Name	Time	Method
Change of Psychological Well Being Index (PGWBI)	6 months from baseline	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	6 months from baseline	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)	6 months from baseline	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.
Change of Maximal Voluntary Strength	6 months from baseline	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	6 months from baseline	Muscle Performance measured using Power of hip and knee extension by Bassey's leg rig.
Change of 6-minute Walking Distance	6 months from baseline	Tests of Physical Function and Task-Specific Performance measured by 6-min walking distance
Change of Stair Climbing Tests	6 months from baseline	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	6 months from baseline	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)	6 months from baseline	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.