The LIFE Study - Lifestyle Interventions and Independence for Elders

As life expectancy in the United States continues to rise, the maintenance of physical
independence among older Americans has emerged as a major clinical and public health
priority. Efficient and reliable locomotion, or the ability to move without assistance, is a
fundamental feature of human functioning. Older people who lose mobility are less likely to
remain in the community, have higher rates of morbidity, mortality, and hospitalizations and
experience a poorer quality of life. Several studies have shown that regular physical
activity improves physical performance, but definitive evidence showing that mobility
disability can be prevented was lacking. A Phase 3 randomized controlled trial was needed to
fill this evidence gap.

The LIFE Study was a Phase 3, multicenter randomized controlled trial (RCT) designed to
compare a moderate-intensity physical activity program to a successful aging health education
program in 1,600 sedentary older persons who are followed for an average of 2.7 years. The
primary outcome was major mobility disability, defined as inability to walk 400 m. Secondary
outcomes include cognitive function based on the Digit Symbol Substitution Test (DSST) and
the Hopkins Verbal Learning Test (HVLT); serious fall injuries; persistent mobility
disability; the combined outcome of major mobility disability or death; disability in
activities of daily living; and cost-effectiveness. Tertiary outcomes include the combined
outcome of mild cognitive impairment or dementia, a composite measure of the cognitive
assessment battery, physical performance within pre-specified subgroups defined on the basis
of race, gender and baseline physical performance, sleep-wake disturbances, dyspnea,
ventilatory capacity, cardiopulmonary events, and cardiovascular events.

The physical activity intervention consists primarily of walking at moderate intensity, lower
extremity resistance exercises, balance exercises, stretching and behavioral counseling. The
successful aging intervention consists of health education seminars regarding health-related
matters and upper extremity stretching exercises. This trial provides definitive evidence
regarding whether physical activity is effective and practical for preventing major mobility
disability. These results will have crucial implications for public health prevention in a
rapidly aging society, and will fill an important gap in knowledge for practicing
evidence-based geriatric medicine. The study will also yield valuable information concerning
the efficacy and effectiveness of physical activity across a broad spectrum of important
health outcomes. The study will impact both clinical practice and public health policy, and
will, therefore, benefit individuals and society.

The Coordinating Center was at the University of Florida and the Data Management Analysis and
Quality Control Center (DMAQC) was at Wake Forest University School of Medicine. The 8 field
sites participating in the LIFE Study are University of Florida, Gainesville, Florida;
Northwestern University, Chicago, Illinois; Pennington Biomedical Research Center, Baton
Rouge, Louisiana; University of Pittsburgh, Pittsburgh, Pennsylvania; Stanford University,
Palo Alto, California; Tufts University, Boston, Massachusetts; Wake Forest University,
Winston-Salem, North Carolina; and Yale University, New Haven, Connecticut.

Inclusion Criteria:

1. age 70 to 89 years; (2) summary score <10 on the short physical performance battery
(SPPB) (45% are <8);90 (3) sedentary lifestyle; (4) ability to complete the 400 m walk
test without an assistive device; and (5) willingness to be randomized to either
intervention group.

Exclusion Criteria:

Exclusion Criteria for Factors that May Limit Adherence to Interventions or Affect
Conduct of the Trial • Unable or unwilling to give informed consent or accept
randomization in either study group • Current diagnosis of schizophrenia, other
psychotic disorders, or bipolar disorder

- Current consumption of more than 14 alcoholic drinks per week

- Plans to relocate to out of the study area within the next 2 years or plans to be
out of the study area for more than 6 consecutive weeks in the next year

- Self-reported inability to walk across a small room

- The use of a walker to complete the 400 m walk and/or unable to complete the 400
m walk without sitting down or the help of another person

- Another member of the household is a participant in the Life Study

- Residence too far from the intervention site

- Residence in a nursing home

- Difficulty in communication with study personnel due to speech or hearing
problems

- Modified Mini-Mental State Exam (3MSE) score below the cutoff for education:

African American, 9+ yrs 76, <9 yrs 70; English Speaking Non-African American, 9+ yrs
80, <9 yrs 76; Spanish Speaking, 9+ yrs 80, <9 yrs 70

- Participation in LIFE-Pilot study

- Other medical, psychiatric, or behavioral factors that in the judgment of the
Principal Investigator may interfere with study participation or the ability to
follow the intervention protocol

Exclusion Criteria for Underlying Diseases Likely to Limit Lifespan and/or Affect the
Safety of the Interventions

• Severe arthritis (either osteoarthritis or rheumatoid arthritis)

• 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)

• Lung disease requiring either regular use of corticosteroid pills or injections or
the use of supplemental oxygen

• Development of chest pain or severe shortness of breath on a 400 m self-paced walk
test

• Cardiovascular disease (including New York Heart Association Class III or IV
congestive heart failure, clinically significant aortic stenosis, history or cardiac
arrest, use of a cardiac defibrillator or uncontrolled angina)

• Parkinson's disease or other serious neurological disorder

• Renal disease requiring dialysis

• Other illness of such severity that life expectancy is considered to be less than 12
months

• Conditions not specifically mentioned above may serve as criteria for exclusion at
the discretion of the clinical site

Temporary Exclusion Criteria

• Uncontrolled hypertension (systolic blood pressure > 200 mmHg and/or diastolic blood
pressure > 110 mmHg).

• Uncontrolled diabetes with recent weight loss, diabetic coma or frequent insulin
reactions.

- Stroke, hip fracture, hip or knee replacement, or spinal surgery in the past 6
months.

- Serious conduction disorder (e.g., 3rd degree heart block), uncontrolled
arrhythmia, or new Q waves or ST-segment depressions (>3 mm) on ECG.

- Myocardial infarction, major heart surgery (i.e., valve replacement or bypass
surgery), stroke, deep vein thrombosis or pulmonary embolus in the past 6 months.

- Undergoing physical therapy or cardiopulmonary rehabilitation

- Currently enrolled in another randomized trial involving lifestyle or
pharmaceutical interventions