The ENRGISE (ENabling Reduction of Low-Grade Inflammation in SEniors) Pilot Study
Condition: Inflammation
MeSH terms: Inflammation
Intervention: Omega-3 fish oil; Losartan; Corn Oil (Fish oil Placebo); Cellulose Based (Losartan Placebo)
Intervention description: 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.; 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.
Intervention MeSH terms: Losartan
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 289.0
Sex: All
Minimum age: 70 Years
Healthy volunteers: No
Keywords: Mobility

Summary:

      ENRGISE Pilot Study will test the ability of anti-inflammatory interventions for preventing
      major mobility disability by improving or preserving walking ability.
    

Eligibility criteria:

        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;

          -  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