Clinical trial NCT01275365: Optimizing Protein Intake in Older Americans With Mobility Limitations
Official title: Optimizing Protein Intake in Older Americans With Mobility Limitations
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Mobility Limitation
Keywords: Mobility Limitation
Low Protein Intake
Older Men
Testosterone
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2011-01-12
Enrollment: 92
Sex: MALE
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Community-dwelling men 65 years of age or older
2. A score of 3-10 on the short physical performance battery (SPPB)
3. Daily protein intake less than the recommended daily allowance of 0.83 g/kg/day (from 3 24-hour food recalls)
4. Able to give informed consent

Exclusion Criteria:

1. History of prostate or breast cancer
2. American Urological Association \[AUA\] symptom index score of \>19
3. Prostate specific antigen (PSA) \>4 ng/ml in White men or \>3 ng/ml in Black men
4. 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.
5. Myocardial infarction or stroke within the last 6 months
6. Uncontrolled congestive heart failure, based on the study physician's evaluation
7. Serum creatinine \> 2.0 mg/dL; men on any kind of dialysis will be excluded.
8. History of celiac disease, Crohn's disease, or ulcerative colitis
9. 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.
10. Neuromuscular diseases: motor neuron diseases, multiple sclerosis, adult muscular dystrophies, and myasthenia gravis
11. 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.
12. Schizophrenia, bipolar disorder, or untreated diagnosed depression. Subjects with unipolar depression who are on an antidepressant medication are eligible.
13. TSH levels \<0.4 or \>5 mlU/L
14. Systolic blood pressure (BP) \>160 or diastolic BP \>100 mm Hg (average of 2 measurements taken at Visit 1)
15. 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.
16. Mini-Mental Status Exam \[MMSE\] \<24
17. Body mass index (BMI) less than 20 or greater than 40 kg/m2
18. Not willing to eat all of the following: red meat, eggs, poultry, fish and shellfish
19. Allergy to sesame, peanuts, soy, gluten or shellfish
20. Current alcohol use \>21 drinks/week based on self-report
21. Confinement to a wheelchair
22. Use of anabolic therapies (Testosterone, DHEA, androstenedione, rhGH) within the past year
23. Current use of levodopa or anticoagulants
24. Current enrollment in a structured weight management program or participation in any weight intervention studies in the last 90 days
25. Serum ALT and AST greater than 3 x upper limit of normal
26. Hematocrit \< 30% or \>48%
27. Subject is not able to eat 3 frozen study meals per day for 6 months
28. Subject is unwilling to stop current nutritional supplements
29. Progressive intensive resistance training within 12 weeks of screening
30. Non-compliant with run-in diet and/or supplement

Primary outcomes:
measure: Change in Lean Body Mass as Measured by Dual Energy X-ray Absorptiometry (DXA)
timeFrame: 6 months from baseline
Secondary outcomes:
measure: Change of Maximal Voluntary Strength
timeFrame: 6 months from baseline
measure: Change of Leg Press Power
timeFrame: 6 months from baseline
measure: Change of 6-minute Walking Distance
timeFrame: 6 months from baseline
measure: Change of Stair Climbing Tests
timeFrame: 6 months from baseline
measure: Change of 50-meter Loaded Walking Test
timeFrame: 6 months from baseline
measure: Change of Self-reported Physical Function Domain of Short Form Health Survey (SF-36)
timeFrame: 6 months from baseline
measure: Change of Psychological Well Being Index (PGWBI)
timeFrame: 6 months from baseline
measure: Change of Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale
timeFrame: 6 months from baseline
measure: Change of Derogatis Affective Balance Scale (DABS)
timeFrame: 6 months from baseline
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Shalender Bhasin, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.