Efficacy of Nutritional Supplementation on Physical-activity Mediated Changes in Physical Functioning Older Adults at Risk for Mobility Disability (The VIVE2 Study)

Exercise Intervention: Participants will complete exercise sessions 3 times per week for 6
months. The exercise sessions will involve walking, lower extremity strength exercises,
flexibility, and balance training.

Supplement Intervention: Participants will be randomly assigned to receive either the
nutritional supplement or placebo. The participants will consume on beverage immediately
after each exercise session.

Primary Outcome: The primary outcome will be the time to walk 400 meters, expressed as
average gait speed during the 400 M walk. All participants must be able to walk 400 meters
in <15 minutes at walking at their normal speed. The 400 M walk will be assessed at
baseline, 3-months, and 6-months, with the changes at 6-months being the primary outcome.

Secondary Outcome Measures:

- Stair Climb Test

- Body Composition

- Skeletal muscle cross sectional area

- Isokinetic/Isometric peak torque/power

- Hand-grip strength

- Nutritional status

- Quality of Life/Depressive symptoms Expected enrollment: 150 (80 at Tufts University
(Boston, MA, USA), 70 at University of Uppsala (Uppsala, Sweden))

Inclusion Criteria:

1. Male & Female ≥ 70 yrs

2. Community dwelling

3. Short Physical Performance Battery ≤ 9

4. Willingness to be randomized and come to the laboratory for 6 months

5. Body Mass Index < 35

6. Mini-Mental State Examination >=24

7. Serum 25 (OH) D (22.5 -50 nmol/l)

8. Having obtained his/her informed consent

9. Able to complete 400 M walk within 15 minutes

Exclusion Criteria:

- • Acute or terminal illness; terminal illness with life expectancy less than 12
months, as determined by a physician

- Current regular use (> 1 per week) of high protein oral nutritional supplements
(eg: Boost, Exceed etc…)

- Current use of Vitamin D supplements, >800 IU/day

- Myocardial infarction in previous 6 months, symptomatic coronary artery disease,
or congestive heart failure.

- Upper or lower extremity fracture in previous 6 months.

- Hemoglobin < 10 g/dL, Estimated GFR < 30 mL/min/1.73 m2

- Uncontrolled hypertension (>150/90 mm Hg).

- Neuromuscular diseases and drugs which affect neuromuscular function; severe
progressive, degenerative neurologic disease

- Hormone replacement therapy

- Insulin-dependent diabetes mellitus

- Milk protein allergy

- Major surgery in the past 6 months (requiring general anesthesia)

- Other significant co-morbid disease that would impair ability to participate in
the exercise-based intervention, e.g. renal failure on hemodialysis, severe
psychiatric disorder (e.g. bipolar, schizophrenia)

- Excessive alcohol use (>14 drinks per wk)

- Participation in moderate intensity physical activity > 20 minutes/week

- Inability to communicate due to severe, uncorrectable hearing loss or speech
disorder

- Severe visual impairment (if it precludes completion of assessments and/or
intervention)

- Severe rheumatologic or orthopedic diseases, e.g., awaiting joint replacement,
active inflammatory disease; wheelchair bound

- Cancer requiring treatment in the past three years, except for non-melanoma skin
cancers or cancers that have clearly been cured or in the opinion of the
investigator carry an excellent prognosis (e.g., Stage 1 cervical cancer)

- Severe pulmonary disease, requiring either steroid pills or injections or the
use of supplemental oxygen

- Severe cardiac disease, including NYHA Class III or IV congestive heart failure,
clinically significant aortic stenosis, history of cardiac arrest, use of a
cardiac defibrillator, or uncontrolled angina

- Patient who cannot be expected to comply with treatment, as decided by the
Principal Investigator and study physician.

- Conditions not specifically mentioned above may serve as criteria for exclusion
at the discretion of the clinical site Principal Investigator and/or study
physician.