Immune Function and Muscle Adaptations to Resistance Exercise in Older Adults

Status:Active, not recruiting
Conditions:Healthy Studies, Infectious Disease, Orthopedic
Therapuetic Areas:Immunology / Infectious Diseases, Orthopedics / Podiatry, Other
Age Range:60 - 80
Start Date:July 23, 2014
End Date:September 30, 2019

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The loss of muscle mass and strength due to aging leads to serious health problems for older
adults. Muscle health can be improved by exercise training, but some people improve their
strength substantially, whereas others improve little. The reason for this variation is
unknown. This study will investigate whether function of the immune system influences how
well people respond to exercise. Older Veterans who participate will have their muscle size,
strength, and function measured periodically for almost a year. Participants will drink a
nutritional supplement or placebo daily and complete a 36 session strength training program.
Participants will be vaccinated for tetanus and donate small amounts of blood and muscle
tissue during the study so that immune function can be compared to muscle outcomes during
training and during a long-term follow-up. The study results should increase the
investigators' understanding of the negative effects of aging on muscle and will possibly
lead to better strategies for muscle maintenance and rehabilitation for older adults.

Objective: The study will examine the influence of immune function in older adults on
improvement of muscle mass, strength, and function by resistance training. The maintenance of
those benefits during long term follow-up will also be examined. This objective will be
accomplished by a double-blind randomized placebo-controlled trial of a nutritional
supplement (Muscle Armor) which evidence suggests can improve immune function, promote muscle
growth, and counteract muscle loss. The study premise is that aging results in decreased
ability of the immune system to respond to stimuli such as exercise. The study proposes that
the supplement will improve muscle health by promoting a shift in immune function of older
adults from a pro-inflammatory state towards a state which supports muscle growth and

Research Plan: The study will randomize Veterans (age 60-80, N=50) to participate in the
supplement or placebo groups in a three phase study. The phases of participation correspond
to the three specific aims. Aim 1 will determine if 2-weeks of supplementation improves
immune function. Humoral immune function will be assessed as the response to vaccination.
Innate immune function will be measured as systemic and cellular responses to acute
resistance exercise that the investigators' previous studies indicate are affected by aging.
Aim 2 will determine if supplementation during 36 sessions of progressive high-intensity
resistance training boosts improvement in muscle size (CT scan), strength, and function (gait
and balance). Muscle adaptations at the cellular levels will also be measured. Aim 3 will
determine if continued supplementation for 26-weeks after completion of exercise training
promotes the retention of the gains in muscle size, strength, and function. Multivariable
testing will then be used to compare the results between Aims 1, 2, and 3 to determine
whether or not immune function is correlated with muscle adaptation to training or

Methods: Participants will undergo nine blood draws and five muscle biopsies of the vastus
lateralis over the course of the study so that the effects of the supplement on immune
function and cellular adaptations to training can be measured. Three of the blood draws will
be used to assess the antibody response to the tetanus, pertussis, and diphtheria vaccine.
Muscle and blood will be collected before and after a bout of exercise conducted before and
after the 2-weeks of supplementation prior to training. Immune function will be measured
using the blood based on pro- and anti-inflammatory cytokine levels, the balance between
specific T-cell subpopulations, and the proliferative capacity of mononuclear cells. Immune
function will be measured in muscle based on macrophage content of specific cytokines and
growth factors. The investigators' previous study showed that these muscle measures strongly
correlate with size and strength gain after training. Key signaling pathways including
nuclear factor-k B and PI3 kinase will also be measured. The fifth biopsy will be collected
post-training to measure adaptation at the cellular level based on changes in number of
satellite cells and myonuclei and fiber size. Hypotheses related to these measures will be
tested with 80% power to detect at least 0.8 standard deviations difference in means between
the supplement and placebo groups.

Clinical Relevance: Exercise is clearly able to affect immune function. However, the proposed
study will attempt to modulate immune function and determine the effects on exercise
outcomes. The study will also examine detraining, an important issue for older adults, that
is usually omitted from training studies. Thus, the study will potentially advance the
understanding of the mechanisms of muscle gain and loss in older adults, but more
importantly, the study will evaluate a nutritional intervention as a complement to exercise
for supporting muscle health during aging. Targeting the immune system may be the advantage
needed for an older Veteran to successfully maintain or restore the muscle mass, strength,
and function that is necessary for personal independence.

Inclusion Criteria:

- Veteran

- Age 60-80 years

- Body Mass Index of 18.5 - 29.9 kg/m2

Exclusion Criteria:

- Currently participating in any other research study involving an intervention

- Smokes tobacco products

- Tetanus or TDAP vaccine in previous two years

- Allergic to vaccination

- Seizure in past 3 months

- Guillain-Barre Syndrome in past 3 months

- Takes the medications heparin, plavix / clopidogrel, or coumadin / warfarin

- Allergic to lidocaine

- Significant problem with fainting

- Problems walking or exercising with both legs

- Participated in a weight-lifting program targeting the thighs in last 3 months

- Pains, tightness or pressure in chest during physical activity

- Metastatic cancer or undergoing chemotherapy

- Cerebral aneurysm or intracranial bleed in past year

- End-stage congestive heart failure (NYHA Stage IV)

- Unstable abdominal or thoracic aortic aneurysm (>4cm)

- Renal disease requiring dialysis

- Allergic to vaccination

- Acute retinal hemorrhage or ophthalmologic surgery in past 3 months

- Bone fractures in the pelvis, legs, or feet in the last 3 months

- Hernia that causes pain during physical activity

- Myocardial infarction or cardiac surgery in past 3 months

- Pulmonary embolism or deep venous thrombosis in past 3 months

- Proliferative diabetic retinopathy or severe nonproliferative retinopathy

- Active suicidality or suicidal ideation

- Systemic bacterial infection

- Taking aspirin in any form and unable/unwilling to discontinue at least 10 days prior
to muscle biopsy

- Unwilling to halt concurrent use of amino acid or protein supplements

- Unwilling to halt new use of nutritional supplements

- Unwilling to maintain current normal diet

- Encephalopathy in past 7 days

- Active oral or genital herpes

- Current use of appetite stimulants

- Current treatment for mania or bipolar disorder or taking lithium.

- Diagnosis of a significant cognitive deficit

- Untreated severe aortic stenosis

- Uncontrolled diabetes mellitus (HbA1C>10)

- Uncontrolled hypertension or hypotension (>160/100, <100 systolic)

- Uncontrolled malignant cardiac arrhythmia

- Unstable angina

- Allergic to latex or tape

- Bleeding or clotting disorders

- Taking any non-ASA NSAID and unable or unwilling to discontinue use for 3 days prior
to muscle biopsy

- Taking Fish Oil, Gingko, Garlic, Saw Palmetto, Turmeric, or Vitamin E and unable or
unwilling to discontinue use for 10 days prior to the muscle biopsy procedure

- Significant problems with chronic pain

- Uncontrolled asthma or allergies

- Taking lactulose, nitrates plus hypertension medications or Viagra

- Liver cirrhosis or other severe liver disease

- History of peripheral artery disease

- Certain Steroid or androgen use in past 3 months

- Other physician judgment

- Significantly abnormal complete blood count (CBC) or prothrombin time (PT)/partial
thromboplastin time (PTT)/international normalized ratio (INR)
We found this trial at
North Little Rock, AR
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