Improving Muscle for Functional Independence Trial

Study Overview
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Brief Summary
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Aging is associated with declines in muscle strength, power, and overall functional ability that lead to disability and loss of independence. Furthermore, the existing high prevalence of obesity in the elderly is greatly exacerbating these aging-related declines in function. To date, regular exercise, especially resistance exercise, is the only known treatment to consistently improve muscle function and perhaps delay the onset of disability. However, not all individuals experience the same magnitude of benefit from a given exercise stimulus, and accumulating data show that obesity limits muscle adaptations to chronic exercise.Therefore, the proposed study is designed to determine the effects of caloric restriction on improvements in skeletal muscle function in response to RT.

Detailed Description
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Design Overview: This is a 5-month randomized trial in 130 older, overweight or obese, sedentary men and women. Phase 1 involves recruitment and screening followed by baseline research testing (Phase 2). Next, subjects will be randomly assigned to one of two 5-month treatments (Phase 3): RT intervention alone (RT) or to an RT with caloric restriction (RT+CR) intervention. Subjects will return for visits the completion of their 5 month intervention. A subset of participants (n=30) will return for an 18 month follow up. Interventions: Resistance training+ Caloric Restriction:Participants assigned to RT+CR group will be instructed to follow a hypocaloric diet (-600 kcal/d) for 20 weeks, as well as the resistance training program noted below.In addition, all participants will be provided with a daily calcium (1200 mg/d) and vitamin D (800 IU/d) supplement.The intervention will incorporate meal replacements, nutrition education, and lifestyle behavior modifications. Resistance training: The maximal weight that can be lifted with correct form in a single repetition (1RM) will be used to prescribe intensity. Strength testing will be repeated every 4 wks and the training loads adjusted so that they are consistent with the 70% 1RM goal. Participants will exercise 3 d/wk on Nautilus resistance machines, under the supervision of two exercise leaders who are trained in basic life support and in emergency management procedures. All exercise will take place at Wake Forest University's Department of Health and Exercise Science Clinical Research Center (CRC). Participants will exercise in small groups which will allow a rotation/rest between machines and enhance the social environment. Heart rate and blood pressure will be measured before and after each session. Subjects will warm-up by walking or cycling for 5 minutes at a slow pace followed by large muscle flexibility exercises. The interventionists will ensure that participants adjust the equipment appropriate to their body size and complete the exercises with correct form. Training sessions will end with a cool-down by walking or cycling for 5 minutes at a slow pace followed by light stretching.

Official Title
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Improving Muscle for Functional Independence Trial

Conditions
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Obesity

Intervention / Treatment
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* Behavioral: Resistance Training
* Behavioral: Resistance Training + Diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BMI=27-34.9 kg/m2 No resistance training for past 6 mos Normal cognitive function (MMSE >24) No contraindications for participation in weight loss or resistance exercise including severe arthritis or musculoskeletal disorders, knee or hip replacement or spinal surgery in past year No broken bones in the past 6 months Able to provide own transportation to study visits and intervention Not involved in any other research study and not undergoing physical therapy Not dependent on a cane or walker Exclusion Criteria: Weight loss or gain (±5%) in past 6 months Body mass >136 kg (DXA limit) Current smoker (No nicotine within past year) or evidence of alcohol or drug abuse Insulin dependent or uncontrolled diabetes (FBG >140 mg/dL) Uncontrolled hypertension (BP>180/100 mmHg) Abnormal kidney function or liver blood tests Past or current cardiovascular disease, including uncontrolled angina or dysrhythmia, hypertrophic cardiomyopathy, congestive heart failure, PAD, stroke, history of myocardial infarction, use of defibrillator or major heart surgery, or deep vein thrombosis or pulmonary embolus Past or current respiratory disease (requiring steroid treatment or supplemental oxygen) Past or current clinical diagnoses of neurological or hematological disease Use of any medications that could influence study variables (growth/steroid hormones, prescription anti-inflammatory medications, or beta blockers, Coumadin or any other blood thinner, including Plavix, Ticid, and Aggrenox) Cancer requiring treatment in past 2 years, except non-melanoma skin cancers Clinically evident edema or anemia

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1. Resistance Training<br>3 d/wk resistance training | Behavioral: Resistance Training<br>* 3 d/wk resistance training<br>* Other names: Nautilus resistance machines;|
| Experimental: 2. Resistance Training + Diet<br>Resistance training plus caloric restriction | Behavioral: Resistance Training + Diet<br>* 3 d/w resistance training plus 600 kcal/d deficit<br>* Other names: RT+CR;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Skeletal muscle function (muscle quality and muscle power) and overall physical function (SPPB score) |  | 5 month study with baseline and 5 and 18 month follow up assessment visits | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| single-fiber contractile force and power, intramyocellular lipid (IMCL), muscle gene and protein expression of interleukin-6 (IL-6) and tumor necrosis factor alpha. |  | baseline and 5 and 18-month follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity, Overweight, Older adults, resistance training, exercise