Impact of Weight Loss on Physical Function

We are proposing a trial to directly compare a high intensity weight loss protocol to a
moderate intensity weight loss protocol to determine which leads to greater improvements in
physical function in severely obese older adults. We are also interested in comparing the
safety of the two approaches. If we can demonstrate effective weight reduction that happens
with sufficient expediency and impact to improve physical functioning without increasing
adverse events in severely obese older adults, a sizable percentage of the population would
benefit and there would be significant reductions in disability resulting in cost savings for
the healthcare system.

This application specifically addresses objective 3 as detailed in the announcement of this
pilot funding mechanism (Objective 3. To develop and reliably test in clinical or
pre-clinical studies novel interventions which target adiposity, peripheral or central
nervous system, vascular, body composition and/or musculoskeletal related factors for
preventing the age-related decline in physical function and preventing or reversing the
progression to disability). This application describes a pilot randomized, controlled trial
designed to address the following aims:

- Assess efficacy and safety of high intensity medical weight management in severely obese
(= stage II BMI) older adults for functional outcomes (i.e., functional weight loss)
compared to a moderate intensity weight loss intervention.

- Determine if a potential dose response relationship exists between weight loss volume
(primarily as excess fat) and improvements in several measures of physical function.

- Identify changes in body composition (fat and lean including bone) that are associated
with changes in physical function.

- Identify biomarkers (specific focus on markers of inflammation) that provide potential
mechanistic links between weight reduction and changes in physical function in severely
obese older adults.

Our primary hypothesis is that there is a greater improvement in physical function with a
high intensity weight loss intervention compared to a moderate intensity intervention.

Inclusion Criteria:

- At least 65 years old at the time of the initial screening visit

- BMI greater than or equal to 35 kg/m2

Exclusion Criteria:

- Cognitive impairment (Montreal Cognitive Assessment < 20)

- Depression (Centers for Epidemiologic Studies Depression Scale score >16

- Recent weight change (+/- 10 lbs. in the last 12 months)

- History of non-skin cancer in the last 2 years

- Cardiovascular disease event or unstable angina within the past six months, severe
pulmonary disease, renal failure

- Major liver dysfunction within the last 2 years

- Recently quit smoking less than 12 months prior

- Use of estrogen or testosterone replacement therapy

- Current use of medications for psychosis or manic-depressive illness

- Use of weight-loss medications in previous 3 months

- Dependence on others for food procurement or preparation

- Poorly controlled diabetes (HgA1c greater than or equal to 9%) or blood pressure
(greater than or equal to 159 mm Hg systolic or 99 mm Hg diastolic)