SarcopeniaTDAP2NCT02261961
Immune Function and Muscle Adaptations to Resistance Exercise in Older Adults
A study testing TDAP, Acute Resistance Exercise and Resistance Exercise Training in people with Sarcopenia and Aging, run by VA Office of Research and Development at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 60 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Sarcopenia, Aging, Immune Function
- What is being tested?
- TDAP, Acute Resistance Exercise and Resistance Exercise Training
- Type of treatment
- Vaccines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 59 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Jul 2014to 30 Sep 2019
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Veteran
- Age 60-80 years
- Body Mass Index of 18.5 - 29.9 kg/m2
Who cannot join
- 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
Show all 52Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
Central Arkansas Veterans Healthcare System Eugene J. Towbin Healthcare Center, Little Rock, AR
North Little Rock, Arkansas, 72114-1706
About this study
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.
Read the detailed description
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 maintenance.
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 detraining.
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.
- Conditions
- Sarcopenia, Aging, Immune Function
- Being tested
- TDAP, Acute Resistance Exercise, Resistance Exercise Training, Post-training Follow-up, Nutritional Supplement (Muscle Armor)
- Keywords
- resistance exercise, Juven, exercise training, interleukin-1, insulin-like growth factor
- Medical subject headings
- Sarcopenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TDAPBiological
Also called tetanus, diptheria, and pertussis vaccination
Both arms will receive the tetanus, diptheria, and pertussis vaccination after two weeks of treatment with supplement or placebo
Acute Resistance ExerciseOther
Also called Single bout of exercise
Both arms will receive a single bout of resistance exercise twice, before and after two weeks of treatment with supplement or placebo, and be evaluated for the response within blood and muscle
Resistance Exercise TrainingOther
Also called Chronic exercise
Both arms will receive 36 sessions of progressive high-intensity resistance exercise training (thigh muscle) over the course of approximately 12 weeks.
Post-training Follow-upOther
Also called Detraining Period
Both arms will continue to receive treatment with supplement or placebo for approximately 26 weeks after completion of the exercise training. During this time subjects will not be allowed to perform resistance exercise.
Nutritional Supplement (Muscle Armor)Dietary supplement
Subjects in the supplement group will consume orange-flavored Muscle Armor according to the manufacturer's directions: one serving (approximately 30g, i.e. one scoop provided with the product by its manufacturer), twice daily mixed with 12 ounces (oz) of water beginning after all baseline assessments are performed including assessment of the response to acute exercise and continuing until the end of study participation.
Placebo (Kool-Aid)Dietary supplement
Subjects in the placebo group will consume orange-flavored Kool-Aid (Kraft Foods) according to the manufacturer's directions: one serving (approximately 13g, i.e. one scoop provided with the product by the pharmacy), twice daily mixed with 12 ounces (oz) of water beginning after all baseline assessments are performed including assessment of the response to acute exercise and continuing until the end of study participation.
| Study group | Role | What they receive |
|---|---|---|
| Nutritional Supplement | Experimental | Subjects in the supplement group will consume orange-flavored Muscle Armor according to the manufacturer's directions: one serving (approximately 30g, i.e. one scoop provided with the product by its manufacturer), twice daily mixed with 12 ounces (oz) of water beginning after all baseline assessments are performed including assessment of the response to acute exercise and continuing until the end of study participation. Receives: Biological: TDAP; Other: Acute Resistance Exercise; Other: Resistance Exercise Training; Other: Post-training Follow-up; Dietary Supplement: Nutritional Supplement (Muscle Armor) |
| Placebo | Placebo comparator | Subjects in the placebo group will consume orange-flavored Kool-Aid (Kraft Foods) according to the manufacturer's directions: one serving (approximately 13g, i.e. one scoop provided with the product by the pharmacy), twice daily mixed with 12 ounces (oz) of water beginning after all baseline assessments are performed including assessment of the response to acute exercise and continuing until the end of study participation. Receives: Biological: TDAP; Other: Acute Resistance Exercise; Other: Resistance Exercise Training; Other: Post-training Follow-up; Dietary Supplement: Placebo (Kool-Aid) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Plasma Concentration of Antibodies to Pertussis Antigen (1 Week Post-vaccine)
The change in plasma antibody concentration for response to the pertussis antigen within the tetanus, diphtheria, and pertussis (TDAP) vaccination will be measured between baseline and one week post-vaccination.
Measured: change from baseline at 1 week post-vaccine
Change in Plasma Concentration of Antibodies to Pertussis Antigen (2 Weeks Post-vaccine)
The change in plasma antibody concentration for response to the pertussis antigen within the tetanus, diphtheria, and pertussis (TDAP) vaccination will be measured between baseline and two weeks post-vaccination.
Measured: change from baseline at 2 weeks post-vaccine
Change in Plasma Concentration of C-Reactive Protein
Plasma c-reactive protein will be measured before and after two weeks of treatment with supplement or placebo.
Measured: change from baseline at 2 weeks of treatment
Change in the Number of Muscle Macrophages Per Myofiber (Pre- to Post-acute Exercise)
The change in the number of muscle macrophages per myofiber will be calculated for muscle collected before and 72 hours after a single bout of resistance exercise. The changes in macrophage numbers before and after two weeks of treatment with supplement or placebo will be compared.
Measured: change from baseline at 2 weeks of treatment
Change in Muscle Strength After Exercise Training for 12 Weeks
The change in muscle strength after exercise training will be measured as the difference in one-repetition maximum capability for knee extension from before and after completion of the exercise training program.
Measured: change from baseline at completion of exercise training phase (12 weeks)
Secondary outcomes (29)
Change in Plasma Concentration of Antibodies to Tetanus Antigen (1 Week Post-vaccine)
The change in plasma antibody concentration for response to the tetanus antigen within the tetanus, diphtheria, and pertussis (TDAP) vaccination will be measured between baseline and one week post-vaccination.
Measured: change from baseline at 1 week post-vaccine
Change in Plasma Concentration of Antibodies to Tetanus Antigen (2 Weeks Post-vaccine)
The change in plasma antibody concentration for response to the tetanus antigen within the tetanus, diphtheria, and pertussis (TDAP) vaccination will be measured between baseline and two weeks post-vaccination.
Measured: change from baseline at 2 weeks post-vaccine
Change in Plasma Concentration of Antibodies to Diptheria Antigen (1 Week Post-vaccine)
The change in plasma antibody concentration for response to the diptheria antigen within the tetanus, diphtheria, and pertussis (TDAP) vaccination will be measured between baseline and one week post-vaccination.
Measured: change from baseline at 1 week post-vaccine
Change in Plasma Concentration of Antibodies to Diptheria Antigen (2 Weeks Post-vaccine)
The change in plasma antibody concentration for response to the diptheria antigen within the tetanus, diphtheria, and pertussis (TDAP) vaccination will be measured between baseline and two weeks post-vaccination.
Measured: change from baseline at 2 weeks post-vaccine
Number of Muscle Macrophages Per Myofiber (Resting)
The number of muscle macrophages per myofiber will be counted for resting muscle collected before and after two weeks of treatment with supplement or placebo.
Measured: change from baseline at 2 weeks of treatment
Change in Muscle Size After Exercise Training for 12 Weeks
The change in size of the thigh muscle group after exercise training will be measured as the difference in cross-sectional area based on CT scan before and after completion of the exercise training program.
Measured: change from baseline at completion of exercise training phase (12 weeks)
Change in Muscle Strength at Week 16 of the Post-Training Period
The change in muscle strength (one-repetition maximum for knee extension) after completion of the exercise training program will be measured during a follow-up period lacking exercise.
Measured: difference between baseline and time point one of de-training follow-up period (week 16)
Change in Balance After Exercise Training for 12 Weeks
The change in balance ability after exercise training will be measured as the difference in Berg Balance Scale (Min 0, Max 56, Higher is Better) score between before and after completion of the exercise training program.
Measured: change from baseline at completion of exercise training (12 weeks)
Change in Balance During the Post-Training Period at 26 Weeks of the Post-training Period
The change in balance based on the Berg Balance Scale (Min 0, Max 56, Higher is Better) score will be measured during a follow-up period lacking exercise after completion of the exercise training program.
Measured: difference between time of training completion and time point two of de-training follow-up period (26 weeks)
Change in Balance at Week 16 of the Post-Training Period
The change in balance based on the Berg Balance Scale (Min 0, Max 56, Higher is Better) score will be measured during a follow-up period lacking exercise after completion of the exercise training program.
Measured: difference between time of training completion and time point one of de-training follow-up period (week 16)
Change in Walking Ability After Exercise Training for 12 Weeks
The change in walking ability after exercise training will be measured using the six minute walk test, i.e. the distance the participant can walk without shortness of breath in six minutes.
Measured: change from baseline at completion of exercise training (12 weeks)
Change in Walking Ability at Week 16 of the Post-Training Period
The change in walking ability based on the six-minute walk test will be measured during a follow-up period lacking exercise after completion of the exercise training program.
Measured: difference between end of training and time point one of de-training follow-up period (week 16)
Change in Walking Ability at Week 26 of the Post-Training Period
The change in walking ability based on the six-minute walk test will be measured during a follow-up period lacking exercise after completion of the exercise training program.
Measured: difference between end of training and time point two of de-training follow-up period (week 26)
Change in Gait Speed After Exercise Training for 12 Weeks
The change in gait speed ability after exercise training will be measured as the difference in habitual walking speed for 10 meters before and after completion of the exercise training program.
Measured: change from baseline at completion of exercise training (12 weeks)
Change in Gait Speed at Week 16 of the Post-Training Period
The change in habitual walking speed over 10 meters will be measured as the difference between values at the end of the training program and time points during a follow-up period lacking exercise.
Measured: difference between after training and time point one of de-training follow-up period (week 16)
Change in Gait Speed During at Week 26 of the Post-Training Period
The change in habitual walking speed over 10 meters will be measured as the difference between values at the end of the training program and time points during a follow-up period lacking exercise.
Measured: difference between after training and time point two of de-training follow-up period (week 26)
Change in Muscle Size at Week 26 of the Post-Training Period
The change in size of the thigh muscle group during the post-training period will be measured as the difference in cross-sectional area based on CT scan at the end of the training program and at the end of study participation.
Measured: difference between baseline and time point two of de-training follow-up period (week 26)
Change in Timed Up and Go After Exercise Training for 12 Weeks
The change in time required to rise from a chair, walk three meters, turn around, walk back to the chair, and sit down will be measured as the difference between before and after completion of the exercise training program.
Measured: change from baseline at completion of exercise training (12 weeks)
Change in Timed Up and Go at Week 16 of the Post-Training Period
The change in time required to rise from a chair, walk three meters, turn around, walk back to the chair, and sit down will be measured as the difference between time points at the end of the training program and during the post-training period.
Measured: difference between after training and time point one of de-training follow-up period (week 16)
Change in Timed Up and Go at Week 26 of the Post-Training Period
The change in time required to rise from a chair, walk three meters, turn around, walk back to the chair, and sit down will be measured as the difference between time points at the end of the training program and during the post-training period.
Measured: difference between after training and time point two of de-training follow-up period (week 26)
Percent Change in Resting Muscle Concentration of Interleukin-1 Beta
The muscle concentration of interleukin-1 beta will be measured before and after two weeks of treatment with supplement or placebo.
Measured: change from baseline at 2 weeks of treatment
Change in Muscle Concentration of Interleukin-1 Beta (Pre- to Post-acute Exercise)
The change in the muscle concentration of interleukin-1 beta before and one hour after a single bout of resistance exercise. The changes in macrophage numbers before and after two weeks of treatment with supplement or placebo will be compared.
Measured: change from baseline at 2 weeks of treatment
Change in Resting Muscle Atrophy Gene MURF Expression
The change in resting muscle atrophy gene MURF expression will be measured before and after two weeks of treatment with supplement or placebo.
Measured: percent change from baseline at 2 weeks of treatment
Change in Resting Muscle Atrophy Gene MURF Expression (Post-acute Exercise)
The change in resting muscle atrophy gene MURF expression will be measured before and 72 hours after a single bout of exercise completed before and after two weeks of treatment with supplement or placebo.
Measured: change from baseline at 2 weeks of treatment
Change in Resting Muscle Protein Kinase B
The change in resting muscle Protein Kinase B will be measured before and after two weeks of treatment with supplement or placebo.
Measured: change from baseline at 2 weeks of treatment
Change in Muscle Protein Kinase B (Post-acute Exercise)
The change in muscle Protein Kinase B will be measured before and 72 hours after a single bout of exercise completed before and after two weeks of treatment with supplement or placebo.
Measured: change from baseline at 2 weeks of treatment
Change in Number of Muscle Satellite Cells After Exercise Training for 12 Weeks
The change in the satellite cell content of muscle will be measured as the difference in the number of satellite cells in muscle before and after completion of the exercise training program.
Measured: change from baseline at completion of exercise training (12 weeks)
Change in Number of Myonuclei After Exercise Training for 12 Weeks
The change in the myonuclear content of muscle will be measured as the difference in the number of myonuclei in muscle before and after completion of the exercise training program.
Measured: change from baseline at completion of exercise training (12 weeks)
Change in Muscle Fiber Size After Exercise Training for 12 Weeks
The change in the muscle fiber size will be measured as the difference in fiber size before and after completion of the exercise training program.
Measured: change from baseline at completion of exercise training (12 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2014 (estimated)
- Study start23 Jul 2014
- Primary completion31 Dec 2018
- Study completion30 Sep 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for SarcopeniaStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 59 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Collaborators
- University of Arkansas
- Responsible party
- Sponsor
- Investigators
- Richard A Dennis, PhD, Principal investigator, Central Arkansas Veterans Healthcare System Eugene J. Towbin Healthcare Center, Little Rock, AR
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02261961
- Sponsor's protocol ID
- E1203-R
- Other IDs
- RX001203, 608119
- Acronym
- TDAP2
- Status last verified
- Aug 2021
- First submitted
- 19 Sep 2014
- Last updated
- 28 Sep 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Long DE, Villasante Tezanos AG, Wise JN, Kern PA, Bamman MM, Peterson CA, Dennis RA. A guide for using NIH Image J for single slice cross-sectional area and composition analysis of the thigh from computed tomography. PLoS One. 2019 Feb 7;14(2):e0211629. doi: 10.1371/journal.pone.0211629. eCollection 2019.
PubMed 30730923Dennis RA, Long DE, Landes RD, Padala KP, Padala PR, Garner KK, Wise JN, Peterson CA, Sullivan DH. Tutorial for using SliceOmatic to calculate thigh area and composition from computed tomography images from older adults. PLoS One. 2018 Oct 2;13(10):e0204529. doi: 10.1371/journal.pone.0204529. eCollection 2018.
PubMed 30278056Kosmac K, Peck BD, Walton RG, Mula J, Kern PA, Bamman MM, Dennis RA, Jacobs CA, Lattermann C, Johnson DL, Peterson CA. Immunohistochemical Identification of Human Skeletal Muscle Macrophages. Bio Protoc. 2018 Jun 20;8(12):e2883. doi: 10.21769/BioProtoc.2883.
PubMed 30148186Dennis RA, Ponnappan U, Kodell RL, Garner KK, Parkes CM, Bopp MM, Padala KP, Peterson CA, Padala PR, Sullivan DH. Immune Function and Muscle Adaptations to Resistance exercise in Older Adults: Study Protocol for a Randomized Controlled Trial of a Nutritional Supplement. Trials. 2015 Mar 27;16:121. doi: 10.1186/s13063-015-0631-3.
PubMed 25872570
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immune Function and Muscle Adaptations to Resistance Exercise in Older Adults
- ClinicalTrials.gov ID
- NCT02261961
- Acronym / sponsor ID
- TDAP2 / E1203-R
- Conditions
- Sarcopenia, Aging, Immune Function
- Keywords
- resistance exercise, Juven, exercise training, interleukin-1, insulin-like growth factor
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 59 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Collaborators
- University of Arkansas
- Study start
- 23 Jul 2014 (actual)
- Primary completion
- 31 Dec 2018 (actual)
- Study completion
- 30 Sep 2019 (actual)
- First posted
- 10 Oct 2014 (estimated)
- Results
- Posted 28 Sep 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 maintenance.
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 detraining.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nutritional Supplement | Experimental | Biological: TDAP, Other: Acute Resistance Exercise, Other: Resistance Exercise Training, Other: Post-training Follow-up, Dietary Supplement: Nutritional Supplement (Muscle Armor)Subjects in the supplement group will consume orange-flavored Muscle Armor according to the manufacturer's directions: one serving (approximately 30g, i.e. one scoop provided with the product by its manufacturer), twice daily mixed with 12 ounces (oz) of water beginning after all baseline assessments are performed including assessment of the response to acute exercise and continuing until the end of study participation. |
| Placebo | Placebo comparator | Biological: TDAP, Other: Acute Resistance Exercise, Other: Resistance Exercise Training, Other: Post-training Follow-up, Dietary Supplement: Placebo (Kool-Aid)Subjects in the placebo group will consume orange-flavored Kool-Aid (Kraft Foods) according to the manufacturer's directions: one serving (approximately 13g, i.e. one scoop provided with the product by the pharmacy), twice daily mixed with 12 ounces (oz) of water beginning after all baseline assessments are performed including assessment of the response to acute exercise and continuing until the end of study participation. |
Who may qualify
- Ages
- 60 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Veteran
- Age 60-80 years
- Body Mass Index of 18.5 - 29.9 kg/m2
Key exclusion criteria (52 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TDAPAlso: tetanus, diptheria, and pertussis vaccinationBoth arms will receive the tetanus, diptheria, and pertussis vaccination after two weeks of treatment with supplement or placebo | Biological | Nutritional Supplement, Placebo |
| Acute Resistance ExerciseAlso: Single bout of exerciseBoth arms will receive a single bout of resistance exercise twice, before and after two weeks of treatment with supplement or placebo, and be evaluated for the response within blood and muscle | Other | Nutritional Supplement, Placebo |
| Resistance Exercise TrainingAlso: Chronic exerciseBoth arms will receive 36 sessions of progressive high-intensity resistance exercise training (thigh muscle) over the course of approximately 12 weeks. | Other | Nutritional Supplement, Placebo |
| Post-training Follow-upAlso: Detraining PeriodBoth arms will continue to receive treatment with supplement or placebo for approximately 26 weeks after completion of the exercise training. During this time subjects will not be allowed to perform resistance exercise. | Other | Nutritional Supplement, Placebo |
| Nutritional Supplement (Muscle Armor)Subjects in the supplement group will consume orange-flavored Muscle Armor according to the manufacturer's directions: one serving (approximately 30g, i.e. one scoop provided with the product by its manufacturer), twice daily mixed with 12 ounces (oz) of water beginning after all baseline assessments are performed including assessment of the response to acute exercise and continuing until the end of study participation. | Dietary supplement | Nutritional Supplement |
| Placebo (Kool-Aid)Subjects in the placebo group will consume orange-flavored Kool-Aid (Kraft Foods) according to the manufacturer's directions: one serving (approximately 13g, i.e. one scoop provided with the product by the pharmacy), twice daily mixed with 12 ounces (oz) of water beginning after all baseline assessments are performed including assessment of the response to acute exercise and continuing until the end of study participation. | Dietary supplement | Placebo |
Primary outcome
Change in Plasma Concentration of Antibodies to Pertussis Antigen (1 Week Post-vaccine)
Time frame: change from baseline at 1 week post-vaccine
The change in plasma antibody concentration for response to the pertussis antigen within the tetanus, diphtheria, and pertussis (TDAP) vaccination will be measured between baseline and one week post-vaccination.
Change in Plasma Concentration of Antibodies to Pertussis Antigen (2 Weeks Post-vaccine)
Time frame: change from baseline at 2 weeks post-vaccine
The change in plasma antibody concentration for response to the pertussis antigen within the tetanus, diphtheria, and pertussis (TDAP) vaccination will be measured between baseline and two weeks post-vaccination.
Change in Plasma Concentration of C-Reactive Protein
Time frame: change from baseline at 2 weeks of treatment
Plasma c-reactive protein will be measured before and after two weeks of treatment with supplement or placebo.
Change in the Number of Muscle Macrophages Per Myofiber (Pre- to Post-acute Exercise)
Time frame: change from baseline at 2 weeks of treatment
The change in the number of muscle macrophages per myofiber will be calculated for muscle collected before and 72 hours after a single bout of resistance exercise. The changes in macrophage numbers before and after two weeks of treatment with supplement or placebo will be compared.
Change in Muscle Strength After Exercise Training for 12 Weeks
Time frame: change from baseline at completion of exercise training phase (12 weeks)
The change in muscle strength after exercise training will be measured as the difference in one-repetition maximum capability for knee extension from before and after completion of the exercise training program.
29 secondary outcomes
Change in Plasma Concentration of Antibodies to Tetanus Antigen (1 Week Post-vaccine)
Time frame: change from baseline at 1 week post-vaccine
Change in Plasma Concentration of Antibodies to Tetanus Antigen (2 Weeks Post-vaccine)
Time frame: change from baseline at 2 weeks post-vaccine
Change in Plasma Concentration of Antibodies to Diptheria Antigen (1 Week Post-vaccine)
Time frame: change from baseline at 1 week post-vaccine
Change in Plasma Concentration of Antibodies to Diptheria Antigen (2 Weeks Post-vaccine)
Time frame: change from baseline at 2 weeks post-vaccine
Number of Muscle Macrophages Per Myofiber (Resting)
Time frame: change from baseline at 2 weeks of treatment
Change in Muscle Size After Exercise Training for 12 Weeks
Time frame: change from baseline at completion of exercise training phase (12 weeks)
Change in Muscle Strength at Week 16 of the Post-Training Period
Time frame: difference between baseline and time point one of de-training follow-up period (week 16)
Change in Balance After Exercise Training for 12 Weeks
Time frame: change from baseline at completion of exercise training (12 weeks)
Change in Balance During the Post-Training Period at 26 Weeks of the Post-training Period
Time frame: difference between time of training completion and time point two of de-training follow-up period (26 weeks)
Change in Balance at Week 16 of the Post-Training Period
Time frame: difference between time of training completion and time point one of de-training follow-up period (week 16)
Change in Walking Ability After Exercise Training for 12 Weeks
Time frame: change from baseline at completion of exercise training (12 weeks)
Change in Walking Ability at Week 16 of the Post-Training Period
Time frame: difference between end of training and time point one of de-training follow-up period (week 16)
Change in Walking Ability at Week 26 of the Post-Training Period
Time frame: difference between end of training and time point two of de-training follow-up period (week 26)
Change in Gait Speed After Exercise Training for 12 Weeks
Time frame: change from baseline at completion of exercise training (12 weeks)
Change in Gait Speed at Week 16 of the Post-Training Period
Time frame: difference between after training and time point one of de-training follow-up period (week 16)
Change in Gait Speed During at Week 26 of the Post-Training Period
Time frame: difference between after training and time point two of de-training follow-up period (week 26)
Change in Muscle Size at Week 26 of the Post-Training Period
Time frame: difference between baseline and time point two of de-training follow-up period (week 26)
Change in Timed Up and Go After Exercise Training for 12 Weeks
Time frame: change from baseline at completion of exercise training (12 weeks)
Change in Timed Up and Go at Week 16 of the Post-Training Period
Time frame: difference between after training and time point one of de-training follow-up period (week 16)
Change in Timed Up and Go at Week 26 of the Post-Training Period
Time frame: difference between after training and time point two of de-training follow-up period (week 26)
Percent Change in Resting Muscle Concentration of Interleukin-1 Beta
Time frame: change from baseline at 2 weeks of treatment
Change in Muscle Concentration of Interleukin-1 Beta (Pre- to Post-acute Exercise)
Time frame: change from baseline at 2 weeks of treatment
Change in Resting Muscle Atrophy Gene MURF Expression
Time frame: percent change from baseline at 2 weeks of treatment
Change in Resting Muscle Atrophy Gene MURF Expression (Post-acute Exercise)
Time frame: change from baseline at 2 weeks of treatment
Change in Resting Muscle Protein Kinase B
Time frame: change from baseline at 2 weeks of treatment
Change in Muscle Protein Kinase B (Post-acute Exercise)
Time frame: change from baseline at 2 weeks of treatment
Change in Number of Muscle Satellite Cells After Exercise Training for 12 Weeks
Time frame: change from baseline at completion of exercise training (12 weeks)
Change in Number of Myonuclei After Exercise Training for 12 Weeks
Time frame: change from baseline at completion of exercise training (12 weeks)
Change in Muscle Fiber Size After Exercise Training for 12 Weeks
Time frame: change from baseline at completion of exercise training (12 weeks)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 30730923Long DE, Villasante Tezanos AG, Wise JN, Kern PA, Bamman MM, Peterson CA, Dennis RA. A guide for using NIH Image J for single slice cross-sectional area and composition analysis of the thigh from computed tomography. PLoS One. 2019 Feb 7;14(2):e0211629. doi: 10.1371/journal.pone.0211629. eCollection 2019.
- Results publication: PubMed 30278056Dennis RA, Long DE, Landes RD, Padala KP, Padala PR, Garner KK, Wise JN, Peterson CA, Sullivan DH. Tutorial for using SliceOmatic to calculate thigh area and composition from computed tomography images from older adults. PLoS One. 2018 Oct 2;13(10):e0204529. doi: 10.1371/journal.pone.0204529. eCollection 2018.
- Results publication: PubMed 30148186Kosmac K, Peck BD, Walton RG, Mula J, Kern PA, Bamman MM, Dennis RA, Jacobs CA, Lattermann C, Johnson DL, Peterson CA. Immunohistochemical Identification of Human Skeletal Muscle Macrophages. Bio Protoc. 2018 Jun 20;8(12):e2883. doi: 10.21769/BioProtoc.2883.
- Results publication: PubMed 25872570Dennis RA, Ponnappan U, Kodell RL, Garner KK, Parkes CM, Bopp MM, Padala KP, Peterson CA, Padala PR, Sullivan DH. Immune Function and Muscle Adaptations to Resistance exercise in Older Adults: Study Protocol for a Randomized Controlled Trial of a Nutritional Supplement. Trials. 2015 Mar 27;16:121. doi: 10.1186/s13063-015-0631-3.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Richard A Dennis, PhD principal investigator
Central Arkansas Veterans Healthcare System Eugene J. Towbin Healthcare Center, Little Rock, AR
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing TDAP, Acute Resistance Exercise and Resistance Exercise Training in people with Sarcopenia and Aging, run by VA Office of Research and Development at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 52 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Sep 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Plasma Concentration of Antibodies to Pertussis Antigen (1 Week Post-vaccine) (time frame: change from baseline at 1 week post-vaccine). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02261961, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2021.