ENRGISE Pilot Study will test the ability of anti-inflammatory interventions for preventing major mobility disability by improving or preserving walking ability.
Growing evidence shows that low-grade chronic inflammation, characterized by elevations in plasma C-reactive protein, tumor necrosis factor alpha, and particularly Interleukin-6 (IL-6), is an independent risk factor of disability, impaired mobility, and lower walking speed. Low-grade chronic inflammation is a modifiable risk factor. However, it is unknown whether interventions that reduce the levels of inflammatory markers per se improve mobility, or avert decline in mobility in older persons. To address this gap in evidence the investigators are conducting the randomized clinical trial ENRGISE (ENabling Reduction of low-Grade Inflammation in SEniors) Pilot Study to test the ability of anti-inflammatory interventions for preventing major mobility disability by improving or preserving walking ability. We have maximized the public health impact by selecting interventions that are safe, tolerable, acceptable, and affordable for vulnerable older persons. Specifically, in this trial the investigators test the efficacy verus placebo of the angiotensin receptor blocker losartan and omega-3 polyunsaturated fatty acids in the form of fish oil, alone and in combination. Both angiotensin receptor blockers and omega-3 polyunsaturated fatty acids have shown to reduce IL-6 in clinical trials and preliminary data suggest that they may improve physical function. Recruitment will include the older persons who are at risk for, or with, mobility impairment, as measured by slow gait speed and self-reported mobility difficulty, and who have elevated levels of IL-6, the marker most consistently associated with mobility limitations. Preliminary data regarding feasibility need to be gathered before such a trial can be effectively designed and implemented. We conduct The ENRGISE Pilot Study to assess the effects of the interventions on several inflammatory markers, walking speed, physical function and strength. This allows us to refine the design, recruitment yields, target population, adherence, retention, tolerability, sample-size, and cost for the main ENRGISE trial.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
TRIPLE
Enrollment
289
The Omega-3 fish oil will be provided in 700 mg gelcaps. The starting dose will be 1.4 g/day of fish oil and continue until the 6 month visit. If the average of IL-6 measured at 3- and 6-month visits does not decrease by \>40% vs. baseline (average of screening visits 1 and 2), we increase the dose to 2.8 g/day.
The Losartan will be provided in 25 mg and 50 mg capsules. The starting dose will be 25 mg/day, if tolerated, then stepped up to 50 mg/day. If there are no safety concerns, a continuation of 50 mg/day will be provided until the 6 month visit. If the average of IL-6 measured at 3- and 6-month visits does not decrease by \>40% vs. baseline (average of screening visits 1 and 2), an increase to the dose of 100 mg/day.
University of Florida
Gainesville, Florida, United States
Northwestern University
Chicago, Illinois, United States
Tufts University
Boston, Massachusetts, United States
Wake Forest University
Winston-Salem, North Carolina, United States
Changes in the Interleukin-6 Level Between Groups
Changes in the Interleukin-6 Level Between the Groups
Time frame: Changes from baseline to month 12
Number of Participants Experiencing Major Mobility Disability
The 400 meter walk test at usual pace is used to evaluate major mobility disability (MMD), defined as the inability to walk ¼ mile or 400 meters.
Time frame: 12 months
Short Physical Performance Battery (SPPB)
A low score on the SPPB based on 4 m walk, balance \& chair stands tests is a risk factor for disability, institutionalization, morbidity and mortality in initially non-disabled older persons. The summary score and components of the SPPB have good reliability (ICCs range from 0.88 to 0.92). Higher scores are better. Range 0-12.
Time frame: 12 months
Number of Participants Exhibiting Frailty
Frailty will be characterized with Fried criteria developed by Fried et al. that employ self-reported exhaustion, unintentional weight loss, low energy expenditure, slow gait speed, and weak grip strength. Those with \>3 of the 5 factors are judged to be frail, those with 1 or 2 factors as pre-frail, and those with no factors as non-frail.
Time frame: 12 months
Isometric Hand Grip Strength
The purpose of this test is to measure the maximum isometric strength of the hand and forearm muscles. Scoring will be taken from the best results of 3 trials. Males scores range from 88 pounds as very poor to 141 pounds as excellent with an average of 105-113 pounds. Females scores range from 44 pounds as very poor to 84 pounds as excellent with an average of 57-65 pounds.
Time frame: 12 months
Peak Torque of the Knee Extensor and Flexor Muscles
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The corn oil placebo gel caps will be identical in shape, color, taste and weight as the Omega-3 fish oil.
The placebo cellulose based capsules will be identical in shape, color, taste and weight as the losartan capsules.
University of Pittsburgh
Pittsburgh, Pennsylvania, United States
Peak torque was measured at a rotational speed of 60 degrees per second using a commercially-available Isokinetic Dynamometer (Biodex). Torque was measured during maximal knee extension and flexion reported in Newton Meters.
Time frame: month 12
Short Form Health Survey (SF-36) - Physical Component Score
The Short Form (36) Health Survey is a 36-item, patient-reported survey of patient health. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Range: 0-100. A lower score indicates more disability, i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Time frame: month 12