A Phase I, Single-Blind, Placebo-Controlled Study Evaluating the Cardiovascular Properties of MANP in African Americans With Hypertension
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- Mayo Clinic
- 试验地点
- 1
- 主要终点
- Change in Blood Pressure
研究概览
简要总结
Evaluate the cardiovascular properties of MANP in AA with Hypertension
详细描述
The study is designed in 2 cycles.
Cycle 1 will incorporate 20 participants and include a screening / enrollment visit and 1 study visit. The study visit will be 30 hours and involves SQ administration of placebo (n=10) or MANP 2.5 ug/kg (n=10). Cycle 2 will incorporate 10 participants and include a screening / enrollment visit and 1 study visit. The study visit will be 30 hours and involves SQ administration of MANP 5 ug/kg (n=10). Studies will be performed at either the CRU of Mayo Clinic's CCaTS in Rochester, Minnesota or the University of Mississippi CRU in Jackson, Mississippi.
All participants will have a screening / enrollment visit where a medical history will be obtained and physical examination performed. At this visit informed consent will also be obtained. Hypertension validation as described above will follow. Once hypertension is validated, subjects will be scheduled for the study visit where either placebo or MANP will be administered at Mayo Clinic's or the University of Mississippi's CRU. Three days prior to the study visit, subjects will be initiated on a moderate sodium (3.0g/day) diet. Fluid intake will be restricted to 2.5 liters per day for all subjects. A 24-hour urine sodium collection will be obtained on the 24 hours prior to the study visit to establish adherence to the low sodium diet. Subjects will be maintained on their standard anti-HTN treatment for the entire duration of the study. At the study visit, subjects will be admitted at 07:00 to the CRU fasting. For safety purposes, all subjects will remain in the CRU a total of 24 hours following dosing. The study will be single blind.
Cycle 1:
At the study visit, either SQ placebo (n=10) or SQ MANP 2.5 ug/kg (n=10) will be administered.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Hypertension, defined as a mean supine BP equal to or greater than 140 mmHg and taking at least one standard of care therapies (including a diuretic, angiotensin converting enzyme inhibitor or angiotensin receptor blocker and a calcium channel blocker);
- •MDRD estimated GFR > 30 mL/min to be calculated at the screening visit by available serum creatinine
- •Male or female African Americans
- •Have a body mass index (BMI) within the range of 18-40 kg/m2;
- •Be able to communicate effectively with the study personnel
- •Be adequately informed of the nature and risks of the study and give written informed consent prior to receiving study medication.
排除标准
- •Known hypersensitivity or allergy to MANP or other NPs;
- •Women of child bearing age
- •Having received any investigational drug or device within 30 days prior to entry into the study; 4) A history (within the last 2 years) of alcohol abuse, illicit drug use, significant mental illness, physical dependence to any opioid, or any history of drug abuse or addiction;
- •A history of difficulty with donating blood or donated blood or blood products within 45 days prior to enrollment;
- •Clinically significant new illness in the 1 month before screening in the opinion of the investigator;
- •History of severe allergies;
- •History of CAD, CVD or syncope;
- •History of epilepsy or other seizure disorder;
- •History of organ transplantation;
- •Malignancy within 5 years;
- •Clinically significant intrinsic renal disease, renal artery stenosis, or history of fibromuscular dysplasia of the renal arteries and;
- •Consumption of a phosphodiesterase-5 inhibitor.
- •Known adrenal insufficiency
- •Subjects with orthostatic hypotension at the screening visit, defined as a decrease in systolic BP of >20 mmHg or a decrease in diastolic BP of >10 mmHg within three minutes of standing when compared with blood pressure from the sitting position.
- •Subjects with a systolic BP >180 mmHg or a diastolic BP >100 mmHg while sitting
研究组 & 干预措施
Placebo - 1st Cycle
Subjects will receive a single SQ injection of placebo (0.9% normal saline) (n=10)
干预措施: Placebo - 1st Cycle (Drug)
MANP - 1st Cycle
Subjects will receive a single SQ injection of 2.5 μg/kg MANP (n=10)
干预措施: MANP - 1st Cycle (Drug)
MANP - 2nd Cycle
Subjects will receive a single SQ injection of 5 μg/Kg MANP (n=10)
干预措施: MANP - 2nd Cycle (Drug)
结局指标
主要结局
Change in Blood Pressure
时间窗: 12 hours
The primary outcome is change in blood pressure 12 hours after MANP or placebo administration compared to the baseline blood pressure. Blood pressure will be measured by an automated arm blood pressure cuff. The unit of measurement is mm Hg. Time frame = 12 hours.
次要结局
- Urinary cGMP excretion(12 hours)
- Urinary sodium excretion(12 hours)
- Glomerular filtration rate(12 hours)
- Plasma aldosterone(12 hours)