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The ENRGISE Pilot Study (ENRGISE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2016 by University of Florida
Sponsor:
Collaborator:
National Institute on Aging (NIA)
Information provided by (Responsible Party):
University of Florida
ClinicalTrials.gov Identifier:
NCT02676466
First received: February 3, 2016
Last updated: February 1, 2017
Last verified: September 2016

February 3, 2016
February 1, 2017
February 2016
March 2018   (Final data collection date for primary outcome measure)
  • Changes in the Interleukin-6 level between the groups performed at baseline, months 3, 6, 9, and 12. [ Time Frame: Changes from baseline to months 3, 6, 9, and 12 ]
    Blood samples will be taken for Interleukin-6 levels between the groups.
  • Changes to the 400 meter walk for major mobility disability will be performed at baseline, months 3, 6, 9, and 12, between the groups [ Time Frame: Changes from baseline to months 3, 6, 9, and 12 ]
    The 400 meter walk test at usual pace is used to find the major mobility disability (MMD), defined as the inability to walk ¼ mile or 400 meters.
Same as current
Complete list of historical versions of study NCT02676466 on ClinicalTrials.gov Archive Site
  • Changes in the Short Physical Performance Battery (SPPB) will be performed at baseline, months 3, 6, 9, and 12, between the groups [ Time Frame: Changes from baseline to months 3, 6, 9, and 12 ]
    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).
  • Changes in frailty will be performed at baseline, months 3, 6, 9, and 12, between the groups [ Time Frame: Changes from baseline to months 3, 6, 9, and 12 ]
    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.
  • Changes in the isometric hand grip strength will be performed at baseline, months 3, 6, 9, and 12, between the groups [ Time Frame: Changes from baseline to months 3, 6, 9, and 12 ]
    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.
  • Changes in the isokinetic dynamometry of the knee extensors and flexors will be performed at baseline and month 12, between the groups [ Time Frame: Changes from baseline to month 12 ]
    This is a device for measuring force, torque, or power. Power is calculated based on rotational speed x torque x constant, with the constant varying with the output unit desired and the input units used.
  • Changes in the Short Form Health Survey (SF-36) will be performed at baseline, months 3, 6, 9, and 12, between the groups [ Time Frame: Changes from baseline to month 12 ]
    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. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
  • Changes in the Short Physical Performance Battery (SPPB) will be performed at baseline, months 3, 6, 9, and 12, between the groups [ Time Frame: Changes from baseline to months 3, 6, 9, and 12 ]
    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).
  • Changes in frailty will be performed at baseline, months 3, 6, 9, and 12, between the groups [ Time Frame: Changes from baseline to months 3, 6, 9, and 12 ]
    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.
  • Changes in the isometric hand grip strength will be performed at baseline, months 3, 6, 9, and 12, between the groups [ Time Frame: Changes from baseline to months 3, 6, 9, and 12 ]
    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.
  • Changes in the isokinetic dynamometry of the knee extensors and flexors will be performed at baseline, months 3, 6, 9, and 12, between the groups [ Time Frame: Changes from baseline to months 3, 6, and 12 ]
    This is a device for measuring force, torque, or power. Power is calculated based on rotational speed x torque x constant, with the constant varying with the output unit desired and the input units used.
  • Changes in the Short Form Health Survey (SF-36) will be performed at baseline, months 3, 6, 9, and 12, between the groups [ Time Frame: Changes from baseline to month 12 ]
    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. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Not Provided
Not Provided
 
The ENRGISE Pilot Study
The ENRGISE (ENabling Reduction of Low-Grade Inflammation in SEniors) Pilot Study
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.

Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Investigator, Outcomes Assessor
Primary Purpose: Prevention
Inflammation
  • Dietary Supplement: Omega-3 fish oil
    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.
  • Drug: Losartan
    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.
    Other Name: Cozaar
  • Other: Placebo
    The corn oil placebo gel caps will be identical in shape, color, taste and weight as the Omega-3 fish oil.
    Other Name: Corn Oil
  • Other: Placebo
    The placebo cellulose based capsules will be identical in shape, color, taste and weight as the losartan capsules.
    Other Name: Cellulose Based
  • Experimental: Omega-3 fish oil
    This group will receive the Omega-3 fish oil which will be administered at a dose of 1.4 grams per day for the first six months. Based on tolerability and inflammation level, dose may either continue at 1.4 grams per day or be increased to 2.8 grams per day for the remaining six month.
    Intervention: Dietary Supplement: Omega-3 fish oil
  • Experimental: Losartan
    This group will receive the Losartan which will be administered at a starting dose of 25 milligrams per day. Based on tolerability, losartan will continue at a dose of either 25 milligrams per day or 50 milligrams per day for the first six months. Based on continued tolerability and inflammation level, dose may either continue at 25 or 50 milligrams per day or be increased to 100 milligrams per day for the remaining six months.
    Intervention: Drug: Losartan
  • Placebo Comparator: Placebo corn oil + cellulose based
    This group will receive a placebo which will be matching to both the omega-3 fish oil and losartan which will be administered at doses corresponding to doses administered for omega-3 fish oil and losartan throughout the 12 month study.
    Interventions:
    • Other: Placebo
    • Other: Placebo
  • Experimental: Omega-3 fish oil + losartan

    This group will receive both the Losartan and Omega-3 fish oil. Losartan will be administered at a starting dose of 25 milligrams per day. Based on tolerability, losartan will continue at a dose of either 25 milligrams per day or 50 milligrams per day for the first six months. Based on continued tolerability and inflammation level, dose may either continue at 25 or 50 milligrams per day or be increased to 100 milligrams per day for the remaining six months.

    Omega-3 fish oil will be administered at a dose of 1.4 grams per day for the first six months. Based on tolerability and inflammation level, dose may either continue at 1.4 grams per day or be increased to 2.8 grams per day for the remaining six month.

    Interventions:
    • Dietary Supplement: Omega-3 fish oil
    • Drug: Losartan
  • Placebo Comparator: Placebo corn oil
    This group will receive a placebo which will be matching to the Omega-3 fish oil. The placebo corn oil are obtained in gel caps and they have identical shape, color, taste and weight. The doses will be administered at doses corresponding to the Omega-3 fish oil.
    Intervention: Other: Placebo
  • Placebo Comparator: Placebo cellulose based
    This group will receive a placebo which will be matching to the losartan. The placebo cellulose based capsule are obtained in 25 mg and 50 mg capsules. The shell capsules are cellulose based. Placebo and LO have identical shape, color, taste and weight. the doses will be administered at doses corresponding to the losartan.
    Intervention: Other: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
300
March 2018
March 2018   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Men and women age >70 years
  • Self-reported difficulty walking ¼ of a mile or climbing a flight of stairs
  • Walking speed <1 meters per second and >0.44 meters per second on the 4 meter walk at usual pace. A walking speed of <0.44 meters per second would not be compatible with completing the 400 meter walk in 15 minutes. (In the pilot phase we explore the feasibility of recruiting at least 50% of participants who have a baseline walking speed of <0.80 meters per second and >0.44 meters per second)
  • Able to complete the 400 meter walk test within 15 minutes without sitting or the help of another person and without a walker, a cane is allowed
  • Blood level IL-6 >2.5 pg/ml and <30 pg/ml.
  • Willingness to be randomized to the intervention groups

Exclusion Criteria:

  • Failure or inability to provide informed consent
  • Lives in a nursing home; persons living in assisted or independent housing are not excluded
  • Self-reported inability to walk one block
  • Significant cognitive impairment, defined as a known diagnosis of dementia, or a Mini-Mental State Exam (MMSE) score <24 (<23 for racial/ethnic minorities or participants with less than 9 years of education)
  • Unable to communicate because of severe hearing loss or speech disorder
  • Neurological conditions that are causing impaired muscle function or mobility (may include stroke with residual paresis, paralysis, neuropathy, Parkinson disease, or multiple sclerosis)
  • Severe rheumatologic or orthopedic diseases, e.g., awaiting joint replacement, known active inflammatory or autoimmune disease (e.g. rheumatoid arthritis, lupus, Crohn's disease, HIV)
  • Terminal illness with life expectancy less than 12 months
  • Severe pulmonary disease, requiring either steroid pills or injections
  • Other significant co-morbid disease that in the opinion of the field center PI would impair ability to participate in the trial, e.g. renal failure on hemodialysis, severe psychiatric disorder (e.g. bipolar, schizophrenia), excessive alcohol use (>14 drinks per week); drug addiction; treatment for cancer (radiation or chemotherapy) within the past 1 year; or other conditions
  • Lives outside of the study site or is planning to move out of the area in next 1 year or leave the area for >3 months during the next year
  • Exclusion criteria that apply only to those who receive losartan:

    • Intolerance or allergy to Angiotensin II Receptor Blockers (ARBs)
    • Known bilateral renal artery stenosis or liver cirrhosis
    • Hypotension Systolic Blood Pressure<110 or Diastolic Blood Pressure<60 mmHg
    • Serum potassium ≥5.0 mEq/L
    • Use of lithium salts
    • eGFR <15
    • Congestive heart failure with ejection fraction < 40%
  • Exclusion criteria that apply only to those who receive ω-3:

    • Intolerance or allergy to ω-3 or fish/shellfish
    • Fatty fish intake >2 servings per week on average
    • History of paroxysmal or persistent atrial fibrillation
  • To maintain blinding, those who are not eligible to receive any active treatment (ω-3 or losartan) are excluded

Temporary exclusion criteria

  • Myocardial infarction, coronary artery bypass grafting (CABG), or valve replacement within past 6 months;
  • Pulmonary embolism or deep venous thrombosis within past 6 months;
  • Uncontrolled diabetes with recent weight loss, diabetic coma, or frequent insulin reactions;
  • Stroke, hip fracture, hip or knee replacement, or spinal surgery within past 4 months;
  • Physical therapy for gait, balance, or other lower extremity training within the past 2 months;
  • Severe hypertension, e.g., Systolic Blood Pressure > 200, or Diastolic Blood Pressure> 110 mmHg;
  • Serum level of 25-OH Vitamin D <20 ng/ml160
  • Hemoglobin <10 g/dL
  • Participation in another intervention trial within 3 months; participation in an observational study may be permitted;
  • Current smoking (within 6 months),
  • Acute infection (urinary, respiratory, other) or hospitalization within 1 month
  • Exclusion criteria that apply only to those who receive losartan:

    • Use of Angiotensin-Converting Enzyme Inhibitor (ACEI), Angiotensin II Receptor Blocker (ARB) within 2 months
    • Use of aliskiren within 2 months in patients with type 2 diabetes or renal impairment with Estimated Glomerular Filtration Rate (eGFR)<60
    • Use of potassium sparing diuretics, other medications with potassium sparing properties (such as but not limited to spironolactone or eplerenone) potassium supplements, and salt substitutes containing potassium within 1 week
    • Transaminases >twice upper limit of normal to exclude participants with impaired liver function
  • Exclusion criteria that apply only to those who receive ω-3:

    • Use of ω-3 within 2 months
Sexes Eligible for Study: All
70 Years and older   (Senior)
No
Contact: Jane Lu 352-294-5853 janelu@ufl.edu
Contact: Michael Stancil 352-294-5854 mstancil@ufl.edu
United States
 
 
NCT02676466
IRB201500894
U01AG050499 ( US NIH Grant/Contract Award Number )
Yes
Not Provided
Yes
The investigator will make the data and associated documentation available to users only under a data-sharing agreement that provides for: (1) a commitment to using the data only for ENRGISE study approved research purposes and not to identify any individual human participant; (2) a commitment to securing the data using appropriate computer technology; and (3) a commitment to destroying or returning the data after analyses are completed.
University of Florida
University of Florida
National Institute on Aging (NIA)
Principal Investigator: Marco Pahor, MD University of Florida
Principal Investigator: Walter Ambrosius, PhD Wake Forest University
University of Florida
September 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP