Allopurinol Improves Diastolic Function in African Americans With Resistant Hypertension
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- LV end-diastolic mid-wall radius to wall thickness ratio
研究概览
简要总结
African American adults in the United States have the highest prevalence rate of high blood pressure (hypertension) and heart failure in the world. African Americans with treatment resistant hypertension have higher levels of the enzyme - xanthine oxidase compared to Caucasians. This trial will test if administration of the xanthine oxidase inhibitor - Allopurinol (commonly used in the treatment of gout), given over a period of 8 weeks, will improve heart function, exercise ability and quality of life in African American Veterans with resistant hypertension.
详细描述
Hypertension among African American adults in the United States has one of the highest prevalence rates in the world and is related to adverse changes in left ventricular (LV) structure and function. Hypertension is an underlying factor in greater than 50% of African American adults with heart failure and is the strongest risk factor in that population. African American adults have a 50% increased incidence of heart failure, due in large part due to the greater prevalence and severity of hypertension.
Heart failure occurs 8 years earlier in African American adults compared with Caucasians. Further, African American adults with heart failure have worse quality of life and depressive symptoms and have a 5-year mortality rate that is 34% higher than in Caucasians. Although African American adults have the highest death rate for heart failure, they are consistently under-represented in clinical trials. The greater heart failure burden among African Americans calls for further work to discover effective preventive and therapeutic strategies for this higher-risk population with heart failure preserved ejection fraction (HFpEF).
An estimated 10-20% of hypertensive patients have resistant hypertension (RHTN), defined as having controlled or uncontrolled blood pressure with the use of 3 or more medications that includes a diuretic. A recent study reported increased plasma xanthine oxidase (XO) activity and mitochondrial DNA damage associated molecular products (mtDAMPs) levels in African American adults with RHTN, compared with Caucasian adults with RHTN. This supports the consensus that oxidative stress is higher in African American adults. Increased xanthine oxidase in heart muscle cells causes a breakdown of muscle structure and a decrease in calcium sensitivity, resulting in left ventricular (LV) dysfunction. A recent study shows that diastolic blood pressure, and other indices of LV diastolic function positively relate to xanthine oxidase activity among African American but not Caucasian RHTN patients.
Given the higher level of xanthine oxidase activity and mtDAMPs in African Americans, the purpose of this clinical trial is to test whether blockade with Allopurinol (for 8 weeks) will improve LV diastolic function, exercise capacity and quality of life metrics in 50 African American Veterans with resistant hypertension.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- •African American
- •Resistant hypertension diagnosis (defined as blood pressure greater than 140/90 millimeters of mercury (mmHg) at 2 clinic visits despite the use of 3 antihypertensive medications at pharmacologically effective doses)
- •Locale - Birmingham, AL and surrounding areas
排除标准
- •History of heart failure
- •Chronic kidney disease (estimated creatinine clearance < 60 milliliters per minute (ml/min)
- •Chronic steroid therapy
- •Known coronary artery disease
- •Known causes of secondary hypertension
- •Already taking Allopurinol
- •Magnetic Resonance Imaging Exclusion
- •Claustrophobia
- •Cardiac implantable electronic device (permanent pacemaker and/or intracardiac defibrillator)
- •Metal clips and/devices or other item that specifically prohibit safe cardiovascular magnetic resonance imaging (CMR)
研究组 & 干预措施
Allopurinol - African American Veterans
Subjects will receive Allopurinol (300mg/daily) for 4 weeks. If tolerated, dose may be increased to 600 milligrams (mg)/daily for an additional 4 weeks. Subjects will take Allopurinol (300-600 milligrams (mg)/daily) for 8 weeks total
干预措施: Allopurinol (Drug)
结局指标
主要结局
LV end-diastolic mid-wall radius to wall thickness ratio
时间窗: 8 weeks
Change from baseline in left ventricular diastolic function index: LV end-diastolic mid-wall radius to wall thickness ratio. Ratio (no units; Range: 1.5-4.0).
LV end-diastolic mass index
时间窗: 8 weeks
Change from baseline in left ventricular diastolic function index: LV end-diastolic mass indexed to body surface area after 8-weeks of treatment with Allopurinol. (Range: 40-100 grams/m2)
LV end-diastolic fractional shortening
时间窗: 8 weeks
Change from baseline in left ventricular diastolic function index: LV end-diastolic fractional shortening after 8-weeks of treatment with Allopurinol. (Range: 15-80%)
Self Reported health survey for Heart Failure
时间窗: 8 weeks
Change in self reported quality of life measures using Kansas City Heart Failure Questionnaire (KCCQ-12) after 8-weeks of Allopurinol. Scale (Minimum - 0 ; Maximum - 100; High score = worse outcome)
Self reported Health Survey
时间窗: 8 weeks
Change in self reported quality of life measures using the Quality of Life Medical Outcomes Study Questionnaire (SF 36 QOL) after 8-weeks of Allopurinol. Scale (Minimum - 0; Maximum - 100; High score = worse outcome)
Normalized peak early diastolic filling rate (E)
时间窗: 8 weeks
Change from baseline in left ventricular diastolic function index: Normalized peak early diastolic filling rate (E) after 8-weeks of treatment with Allopurinol. (Range 1.5 - 3.0 end-diastolic velocity (EDV)/second)
Six minute walk test
时间窗: 8 weeks
Change in exercise capacity by six minute walk test after 8-weeks of Allopurinol. Timed activity for distance walked (Distance range approximately 400-800 meters (m); Further distance = better outcome)
Left ventricular end-diastolic volume index
时间窗: 8 weeks
Change from baseline in left ventricular diastolic function index: left ventricular end diastolic volume normalized to body surface area after 8-weeks of treatment with Allopurinol. (Range 40 - 100 milliliters per square meter (mL/m2)
Normalized peak late diastolic filling rate (A), EDV/s
时间窗: 8 weeks
Change from baseline in left ventricular diastolic function index: Normalized peak late diastolic filling rate (A) after 8-weeks of treatment with Allopurinol. (Range 1.3 - 4.5 end-diastolic velocity (EDV)/second)
Left ventricular (LV) end-diastolic mass index
时间窗: 8 weeks
Change from baseline in left ventricular diastolic function index: LV end-diastolic mass indexed to body surface area after 8-weeks of treatment with Allopurinol. (Range: 40-100 grams/square meter (m2)
Left ventricular (LV) end-diastolic fractional shortening
时间窗: 8 weeks
Change from baseline in left ventricular diastolic function index: LV end-diastolic fractional shortening after 8-weeks of treatment with Allopurinol. (Range: 15-80%)
Left ventricular (LV) end-diastolic mid-wall radius to wall thickness ratio
时间窗: 8 weeks
Change from baseline in left ventricular diastolic function index: LV end-diastolic mid-wall radius to wall thickness ratio. Ratio (no units; Range: 1.5-4.0).
次要结局
- Xanthine Oxidase(8 weeks)
- mitochondrial DNA damage-associated molecular patterns(8 weeks)
- Brain Natriuretic Peptide(8 weeks)
- Systolic Blood Pressure(8 weeks)
- Diastolic Blood Pressure(8 weeks)