Pilot Study of Losartan and N-acetylcysteine as Inhibitors of Muscle Oxidative Stress in Elderly
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Leg Blood Flow as Measured by Doppler Ultrasound
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 60 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age between 60-85 years.
- •Ability to sign informed consent.
- •Ability to sign consent form.
- •Ability to pass a mini-mental status exam (score >23 on the 30-item Mini Mental State Examination, MMSE).
- •Free-living, prior to admission.
排除标准
- •Subjects with cardiac abnormalities considered exclusionary by the study physicians (e.g., unstable angina or a cardiology-confirmed ECG that demonstrates cardiac abnormalities such as > 0.2 mV horizontal or downsloping ST segment depression, frequent arrhythmia's (> 10 PVC/min), or valvular disease).
- •Subjects with uncontrolled metabolic disease, including liver or renal disease.
- •Subjects with vascular disease characterized by a combination of risk factors of peripheral atherosclerosis. (e.g., uncontrolled hypertension, obesity, uncontrolled diabetes, hypercholesterolemia > 250 mg/dl, claudication or evidence of venous or arterial insufficiency upon palpitation of femoral, popliteal, and pedal arteries.
- •Any history of hypo- or hyper-coagulation disorders. (e.g., Coumadin use or history of DVT or PE).
- •Subjects with chronically elevated systolic pressure >170 or a diastolic blood pressure >
- •Subjects may be included if they are taking medication and have a blood pressure below these criteria.
- •Subjects with cancer or recently (6 months) treated cancer other than basal cell carcinoma.
- •Any subject currently on a weight-loss diet or a body mass index > 33 kg/m
- •Inability to abstain from smoking for duration of study.
- •A history of > 20 pack per year smoking.
- •Subjects with atrial fibrillation, history of syncope, angina, or congestive heart failure.
- •Any subject that is HIV-seropositive or has active hepatitis.
- •Recent anabolic or corticosteroids use (within 3 months).
- •Subjects with low hemoglobin or hematocrit (i.e., lower than accepted lab values).
- •Agitation/aggression disorder.
- •History of stroke with motor disability.
- •A recent history (<12 months) of GI bleed.
- •Alcohol (more than 3 drinks per day) or drug abuse.
- •Polycystic ovary syndrome (PCOS) and/or hyperthecosis.
- •Non-classical adrenal hyperplasia.
- •Cushing's syndrome.
- •Hyperprolactinoma, hypothyroidism.
- •Lactose intolerance.
- •Subjects with coronary heart or mitral valvular rheumatic heart disease.
- •Subjects with impaired renal function and/or renal artery stenosis.
- •Subjects with pulmonary hypertension.
- •Subjects on any medications known to vasodilate the peripheral arteries.
- •Subjects taking NSAIDs
- •Physical dependence or frailty (impairment of activities of daily living, ADLs).
- •History of falls (>2/year).
- •Depression (>5 of the 15 items on the Geriatric Depression Scale (GDS).
- •Subjects suffering malnutrition or with a BMI < 20 kg/m2 with low albumin or transferrin.
- •Any other condition or event considered exclusionary by the PI and covering faculty physician.
研究组 & 干预措施
Losartan and placebo N-acetylcysteine
losartan (25mg/dose) and placebo N-acetylcysteine (NAC) 3 total doses: 1 dose on day 1, 2 doses on day 2.
干预措施: Losartan (Drug)
Losartan and placebo N-acetylcysteine
losartan (25mg/dose) and placebo N-acetylcysteine (NAC) 3 total doses: 1 dose on day 1, 2 doses on day 2.
干预措施: Placebo N-acetylcysteine (Drug)
Placebo losartan and placebo N-acetylcysteine
Placebo losartan and placebo N-acetylcysteine (NAC) 3 total doses: 1 dose on day 1, 2 doses on day 2.
干预措施: Placebo losartan (Drug)
Placebo losartan and placebo N-acetylcysteine
Placebo losartan and placebo N-acetylcysteine (NAC) 3 total doses: 1 dose on day 1, 2 doses on day 2.
干预措施: Placebo N-acetylcysteine (Drug)
N-acetylcysteine and placebo losartan
N-acetylcysteine (NAC) (50 mg/kg/dose) and placebo losartan 3 total doses: 1 dose on day 1, 2 doses on day 2.
干预措施: N-acetylcysteine (Drug)
N-acetylcysteine and placebo losartan
N-acetylcysteine (NAC) (50 mg/kg/dose) and placebo losartan 3 total doses: 1 dose on day 1, 2 doses on day 2.
干预措施: Placebo losartan (Drug)
结局指标
主要结局
Leg Blood Flow as Measured by Doppler Ultrasound
时间窗: 2 hours post dose three of the intervention and a meal, average of 19 hours post dose one of the intervention
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. A pulsed-wave Doppler sample blood volume will be placed at the same location in the center of the artery, and the mean blood velocity will be measured using online angle correction and analysis software. Femoral artery mean blood flow will be calculated from 2-D and Doppler ultrasound data using the equation: Q = vπ ∙ (d/2)2, where Q is femoral blood flow, v is mean femoral artery blood flow velocity, and d is femoral artery diameter.
次要结局
- Handgrip Strength of Dominant Hand as Measured by Handgrip Dynamometry at 50% Perceived Effort at Baseline(baseline)
- Handgrip Strength of Dominant Hand as Measured by Handgrip Dynamometry at 50% Perceived Effort After All Doses of Study Intervention(Post dose three of the intervention, average of 17 hours post dose one intervention)
- Handgrip Strength of Non-dominant Hand as Measured by Handgrip Dynamometry at 50% Perceived Effort After All Doses of Study Intervention(Post dose three of the intervention, average of 17 hours post dose one intervention)
- Handgrip Strength of Dominant Hand as Measured by Handgrip Dynamometry at 100% Perceived Effort After All Doses of Study Intervention(Post dose three of the intervention, average of 17 hours post dose one intervention)
- Personal Perceptual Fatigue Measured by Multidimensional Fatigue Symptom Inventory - Subscale Vigor Fatigue at Baseline(Baseline)
- Personal Perceptual Fatigue Measured by Multidimensional Fatigue Symptom Inventory - Subscale Vigor Fatigue After All Doses of Study Intervention(Post dose three of the intervention, average of 17 hours post dose one intervention)
- Perceptual Fatigue of Non-dominant Arm as Measured by Visual Analog Scale Before Handgrip Fatigue Test After Study Intervention(Post dose three of the intervention, average of 17 hours post dose one intervention - Before handgrip fatigue test)
- Handgrip Strength of Non-dominant Hand as Measured by Handgrip Dynamometry at 50% Perceived Effort at Baseline(baseline)
- Handgrip Strength of Dominant Hand as Measured by Handgrip Dynamometry at 100% Effort at Baseline(baseline)
- Handgrip Strength of Non-dominant Hand as Measured by Handgrip Dynamometry at 100% Effort at Baseline(baseline)
- Handgrip Fatigue of Dominant Hand as Measured by Handgrip Dynamometry at Baseline(baseline)
- Handgrip Fatigue of Non-dominant Hand as Measured by Handgrip Dynamometry at Baseline(baseline)
- Handgrip Strength of Non-dominant Hand as Measured by Handgrip Dynamometry at 100% Perceived Effort After All Doses of Study Intervention(Post dose three of the intervention, average of 17 hours post dose one intervention)
- Handgrip Fatigue of Dominant Hand as Measured by Handgrip Dynamometry After All Doses of Study Intervention(Post dose three of the intervention, average of 17 hours post dose one intervention)
- Handgrip Fatigue of Non-dominant Hand as Measured by Handgrip Dynamometry After All Doses of Study Intervention(Post dose three of the intervention, average of 17 hours post dose one intervention)
- Personal Perceptual Fatigue Measured by Multidimensional Fatigue Symptom Inventory - Subscale General Fatigue at Baseline(Baseline)
- Personal Perceptual Fatigue Measured by Multidimensional Fatigue Symptom Inventory - Subscale Physical Fatigue at Baseline(Baseline)
- Personal Perceptual Fatigue Measured by Multidimensional Fatigue Symptom Inventory - Subscale Mental Fatigue at Baseline(Baseline)
- Personal Perceptual Fatigue Measured by Multidimensional Fatigue Symptom Inventory - Total Score at Baseline(Baseline)
- Perceptual Fatigue of Whole Body as Measured by Visual Analog Scale After Handgrip Fatigue Test After Study Intervention(Post dose three of the intervention, average of 17 hours post dose one intervention - Directly after handgrip fatigue test)
- Personal Perceptual Fatigue Measured by Multidimensional Fatigue Symptom Inventory - Subscale General Fatigue After All Doses of Study Intervention(Post dose three of the intervention, average of 17 hours post dose one intervention)
- Personal Perceptual Fatigue Measured by Multidimensional Fatigue Symptom Inventory - Subscale Physical Fatigue After All Doses of Study Intervention(Post dose three of the intervention, average of 17 hours post dose one intervention)
- Personal Perceptual Fatigue Measured by Multidimensional Fatigue Symptom Inventory - Subscale Emotional Fatigue After All Doses of Study Intervention(Post dose three of the intervention, average of 17 hours post dose one intervention)
- Personal Perceptual Fatigue Measured by Multidimensional Fatigue Symptom Inventory - Subscale Emotional Fatigue at Baseline(Baseline)
- Personal Perceptual Fatigue Measured by Multidimensional Fatigue Symptom Inventory - Subscale Mental Fatigue After All Doses of Study Intervention(Post dose three of the intervention, average of 17 hours post dose one intervention)
- Perceptual Fatigue of Whole Body as Measured by Visual Analog Scale Before Handgrip Fatigue Test at Baseline.(baseline - before handgrip fatigue test)
- Perceptual Fatigue of Whole Body as Measured by Visual Analog Scale After Handgrip Fatigue Test at Baseline.(baseline - directly after handgrip fatigue test)
- Perceptual Fatigue of Whole Body as Measured by Visual Analog Scale Before Handgrip Fatigue Test After Study Intervention(Post dose three of the intervention, average of 17 hours post dose one intervention - Before handgrip fatigue test)
- Personal Perceptual Fatigue Measured by Multidimensional Fatigue Symptom Inventory - Total Score After All Doses of Study Intervention(Post dose three of the intervention, average of 17 hours post dose one intervention)
- Global Fatigue Score as Measured by Brief Fatigue Inventory at Baseline(Baseline)
- Global Fatigue Score as Measured by Brief Fatigue Inventory After Study Invention(Post dose three of the intervention, average of 17 hours post dose one intervention)
- Perceptual Fatigue of Non-dominant Arm as Measured by Visual Analog Scale After Handgrip Fatigue Test at Baseline.(baseline - directly after handgrip fatigue test)
- Perceptual Fatigue of Non-dominant Arm as Measured by Visual Analog Scale After Handgrip Fatigue Test After Study Intervention(Post dose three of the intervention, average of 17 hours post dose one intervention - Directly after handgrip fatigue test)
- Perceptual Fatigue of Non-dominant Arm as Measured by Visual Analog Scale Before Handgrip Fatigue Test at Baseline.(baseline - before handgrip fatigue test)