Pilot Study of Losartan and N-acetylcysteine as Inhibitors of Muscle Oxidative Stress in Elderly

Study Summary

The general hypothesis is that elderly have diminished nutritive flow to skeletal muscle and impaired capacity for building muscle. In aging populations, this decreased ability to build muscle may represent a tipping point in the progression towards chronic physical frailty and disability. The goal is to examine whether novel pharmacologic therapies can improve nutritive blood flow to the muscles and muscle building in the elderly. The purpose of this study is 1) to determine if losartan administration will enhance blood flow and 2) to determine if N-acetylcysteine (NAC) will enhance blood flow. The investigators will study community dwelling, healthy older men and women (60-85 years). Subjects will be randomized to one of three groups: Experimental Group 1: Placebo losartan and placebo N-acetylcysteine (NAC). Experimental Group 2: losartan (25mg/dose) and placebo N-acetylcysteine (NAC). Experimental Group 3: N-acetylcysteine (NAC) (50 mg/kg/dose) and placebo Subjects will admit to the clinic on day 1 of the study. Baseline testing consisting of leg blood flow (LBF), contrast enhanced ultrasound, handgrip testing and fatigue questionnaires. After testing is completed the subjects will recieve their first dose of NAC/ losartan/ placebo with dinner. Subjects will be fasted after 10 pm. On day 2, leg blood flow (LBF) will be measured approximately 12 hours post dose 1. Subjects will receive their second dose of NAC/ losartan/ placebo. Leg blood flow will be measured 1 hour and 2 hours post dose 2 of study interventions. The subjects will eat a meal and receive their third dose of the study intervention. Leg blood flow will be repeated at 1 hour and 2 hours post dose 3. Appoximately 30 minutes after dose 3 of the study intervention, handgrip testing will be performed and fatigue questionnaires completed.

Primary Outcome

Femoral Doppler Blood Flow was evaluated via Doppler ultrasound. For the two-dimensional (2-D) and Doppler ultrasound measurements, an ultrasound system (HDI-5000; Philips Medical Systems, Bothell, WA) with a linear array transducer (L7-4) was used with a transmit frequency of 12MHz. 2-D imaging of the common femoral artery will be performed in the long axis. Images will be triggered to the R wave of the cardiac cycle, and the femoral artery diameter will be measured using online video calipers.

Interventions

• DRUG Losartan
• DRUG N-acetylcysteine
• DRUG Placebo losartan
• DRUG Placebo N-acetylcysteine