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Table 1 Inclusion and exclusion criteria for the LACE trial

From: Leucine and ACE inhibitors as therapies for sarcopenia (LACE trial): study protocol for a randomised controlled trial

Inclusion criteria

 Age 70 and over

 Diagnosis of sarcopenia (see Table 2)

Exclusion criteria

 Contraindications or existing indications to therapies or placebo

  Known clinical diagnosis of chronic heart failure (by European Society of Cardiology criteria)

  Confirmed LV systolic dysfunction on any imaging modality

  Known aortic stenosis (peak gradient > 30 mmHg)

  Systolic BP < 90 mmHg (supine)

  Dizziness on standing associated with a postural drop of > 20/10 mmHg (asymptomatic orthostatic hypotension is not a contraindication)

  Serum creatinine > 170 μmol/L or eGFR < 30 ml/min by MDRD4 calculation

  Serum potassium > 5.0 mmol/L

  Serum sodium < 130 mmol/L

  Using ACEi, angiotensin receptor blocker, aldosterone blocker or leucine already (protein supplementation is permitted)

  Previous adverse reaction to ACEi or leucine

  Current use of oral NSAIDs (aspirin is permitted, as are topical NSAIDs)

  Current use of potassium supplements, aliskiren, spironolactone or other potassium-sparing diuretics

  Hereditary or idiopathic angioedema

  Lactose intolerance

 Contraindications to consent or undertaking study outcomes

  Implantable cardioverter defibrillator or pacemaker with atrial sensing lead (pacemakers with ventricular sensing lead only are allowed)

  Peripheral oedema present above knee level

  Unable to mobilise without human assistance (walking aids are allowed)

  Unable to give written informed consent

  Currently enrolled in another intervention research study, or < 30 days since completing another intervention research study. Concomitant enrolment in observational studies is permitted.

 Overlap with other myopathic conditions or important confounders

  Currently enrolled in a time-limited exercise-based rehabilitation programme

  Any progressive neurological or malignant condition with life expectancy < 6 months

  Severe chronic obstructive pulmonary disease (GOLD stage IV)

  Known myositis or other established myopathy

  Self-reported weight loss of > 10% in last 6 months (to exclude significant cachexia)

  Known uncontrolled thyrotoxicosis

  Prednisolone use ≥ 7.5 mg/day (or equivalent dose of other glucocorticoids)

  1. ACEi angiotensin converting enzyme inhibitor, BP blood pressure, eGFR estimated glomerular filtration rate, GOLD Global initiative for chronic Obstructive Lung Disease, LACE Leucine and Angiotensin Converting Enzyme inhibitors in sarcopenia, LV left ventricular, MDRD4 Modification of Diet in Renal Disease 4-component equation, NSAID non-steroidal anti-inflammatory drug