Based upon promising results from a pilot study among 424 sedentary older adults who were randomized to a physical activity intervention or a successful aging health education intervention, a Phase 3 multi-center randomized controlled trial is being conducted to compare a moderate-intensity physical activity program to a successful aging health education program in 1,600 sedentary older adults who are followed for an average of 2.7 years.

The primary aim was to assess the long-term effects of the proposed interventions on the primary outcome of major mobility disability, defined as inability to walk 400 m.

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

If an investigator outside of a LIFE study team would like access to the LIFE coded dataset, this individual must go through the following steps:

1. Request access to the LIFE website for the purposes of submitting a P&P proposal to obtain access to the Coded Datasets by going to the LIFE website (www.thelifestudy.org) and clicking on the button "Request for Non-LIFE investigator Access" and completing the request form.
2. Access would be granted to the LIFE website where access to would be provided to the data dictionary, data documentation, and protocol, in addition to the Manuscript Proposal Submission Form.
3. A proposal would be submitted (per current guidelines) to LIFE and reviewed through the usual channels.
4. If approved the Investigator would be sent a Coded Data Use Agreement document to be signed and sent back to the DMAQC for filing.
5. Access to the Coded Datasets would be granted for a period of 10 days.

Baseline characteristics were similar in the 2 groups.

Adverse events were collected from each participant beginning with screening until closeout of the study. Participants were queried every 6 months but could report adverse events in-between visits. Participants were followed for an average of 2.6 years.

To minimize reporting bias, adverse events originating from the blinded assessments are presented. Blinded assessments were completed every 6 months.

Non-serious AEs were collected without regard to the specific AE term.