Songling Xuemaikang Capsules in Hypertension and Insomnia Evaluation：a Randomized，Double-blind，Placebo-controlled Multicenter Study
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 260
- 试验地点
- 1
- 主要终点
- Change from baseline in 24-hour mean systolic blood pressure at Week 12.
研究概览
简要总结
To evaluate the effect of Songling Xuemaikang Capsules on reducing 24-hour mean blood pressure in patients with hypertension accompanied by insomnia.
详细描述
Disease Background： Hypertension is one of the major chronic non-communicable diseases in China, with an extremely severe epidemic situation, imposing a heavy burden on public health and the national medical system. According to the latest data, the weighted prevalence of hypertension among adults aged ≥18 years in China was 27.5% in 2018. A survey from 2012 to 2015 showed that the awareness, treatment, and control rates of hypertension among people aged over 18 years were 51.6%, 45.8%, and 16.8%, respectively. Healthy sleep includes sufficient sleep duration and good sleep quality. Healthy sleep is associated with a lower risk of hypertension, and with a lower incidence of coronary heart disease and stroke in hypertensive patients. Short sleep duration increases the risk of hypertension, and insomnia is associated with cardiovascular mortality and all-cause mortality. A meta-analysis conducted in 2024 included 32 sleep studies in China involving more than 370,000 participants, assessed by the Pittsburgh Sleep Quality Index (PSQI) with a cutoff score of 4-7 (68.8% of studies used a cutoff of 7 for sleep abnormality). The prevalence of poor sleep quality was found to be 19.0% (95% CI: 15.8%-22.8%). The proportion of sleep problems in the hypertensive population is higher than that in the general population. A meta-analysis published in 2020 included 24 studies involving 13,920 participants, revealing that the prevalence of sleep difficulty in hypertensive individuals was as high as 52.5% (95% CI: 46.1%-58.9%), compared with 32.5% (95% CI: 19.0%-49.7%) in healthy controls. The odds ratio (OR) of sleep difficulty in hypertensive patients was 2.66 (95% CI: 1.80-3.93).
There is a complex pathophysiological link between hypertension accompanied by insomnia, rather than coincidental overlap. Numerous studies have confirmed that insomnia is an independent risk factor for the development and progression of hypertension. Chronic insomnia can elevate blood pressure and heart rate and increase the risk of hypertension through mechanisms such as activating the sympathetic nervous system, disrupting hypothalamic-pituitary-adrenal (HPA) axis function, and promoting inflammatory responses. A meta-analysis showed that the relative risk (RR) of incident hypertension in individuals with insomnia was approximately 1.21. Conversely, hypertension itself and its therapeutic drugs may also cause or worsen insomnia. Hypertensive patients often experience impaired sleep quality due to nocturnal blood pressure fluctuations, excessive sympathetic activation, anxiety, or side effects of certain antihypertensive agents .
Therefore, the Chinese Guidelines for the Prevention and Treatment of Hypertension (2024 Revised Edition) provides specific and practical recommendations for the management of sleep duration and quality, including screening for sleep disorders and blood pressure in targeted populations, and proposes specific measures such as cognitive behavioral therapy for insomnia, hypnotic medications, and reducing diuretic use at night. However, in clinical practice, concerns regarding long-term adherence to cognitive behavioral therapy for insomnia and the safety of long-term use of sedative-hypnotic drugs still compromise the synergistic management of hypertension accompanied by insomnia. Thus, the selection of a medication that can lower blood pressure and improve insomnia simultaneously is of great clinical value.
Drug Background： Songling Xuemaikang Capsule is an exclusive product of Chengdu Kanghong Pharmaceutical Co., Ltd., approved for marketing on February 12, 1996. Its formula consists of Pini Massonianae Folium (fresh pine needle), Puerariae Lobatae Radix (kudzu root), and Concha Margaritifera Usta (nacre powder). Its functions and indications are: calming the liver and suppressing yang, tranquilizing the heart and calming the nerves. It is used for headache, dizziness, irritability, palpitations, and insomnia caused by hyperactivity of liver yang; it is also indicated for hypertension and primary hyperlipidemia with the above symptoms.
The sovereign drug of Songling Xuemaikang Capsule is Pinus massoniana Lamb. (Masson pine), a plant of the Pinus genus in the Pinaceae family. It is widely distributed in the humid eastern subtropical regions of China and extends to the northern tropics. In the lower Yangtze River basin, it occurs below 700 m above sea level; in the middle reaches, below 1,100-1,200 m; and in western China, below 1,500 m. The needle of Pinus massoniana, also known as pine hair, is slender and needle-shaped, hence called "pine needle". The needles are in bundles of two, lanceolate, 12-20 cm long, soft and flexible, with resin canals marginal; young leaves are green, and fallen leaves are brown. When dried, a long and narrow groove appears in the center, showing the leaf characteristics. The surface is smooth, dull green, light and crisp, with a slight odor, astringent and bitter taste, and warm nature. Compendium of Materia Medica records: "Long-term administration of pine needles cures all diseases, calms the five zang-organs, promotes hair growth, resists cold and heat, endures wind and rain, lightens the body and replenishes qi, preserves the interior and prolongs life without grain." Pine needle enters the heart and liver meridians, with effects of dispelling wind and drying dampness, killing parasites and relieving itching, activating blood circulation and calming the nerves. It is commonly used for influenza, rheumatic arthralgia, traumatic swelling and pain, hypertension, hyperlipidemia, neurasthenia, eczema, etc. Modern pharmacological studies have shown that proanthocyanidins and shikimic acid in pine needle exert antihypertensive, lipid-lowering, antioxidant, antipyretic, analgesic, anti-inflammatory, and sedative effects.
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
- 18 Years 至 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-79 years (inclusive), male or female;
- •Meet diagnostic criteria for essential hypertension, and satisfy one of the following conditions:
- •Grade 1 hypertension with no antihypertensive drugs in the past 2 weeks; Receiving stable treatment with one standard-dose chemical antihypertensive agent for at least 4 weeks, with blood pressure（BP）140-159/90-99 mmHg, and is willing to maintain the treatment regimen without adjustment;
- •Insomnia Serverity Index (ISI) score ≥ 8, symptoms occur for at least 3 nights per week and have persisted for no less than 3 months;
- •No sedative-hypnotic drugs have been taken within the preceding one month;
- •Is able to complete scale assessments independently;
- •Is willing and able to comply with all examinations and observations specified in the protocol; Has provided written informed consent.
排除标准
- •Severe hypertension (mean SBP ≥ 180 mmHg and/or mean DBP ≥ 110 mmHg); malignant hypertension, hypertensive emergency, hypertensive crisis, hypertensive encephalopathy, etc.
- •Suspected secondary hypertension (renal parenchymal hypertension, renovascular hypertension, obstructive sleep apnea, primary aldosteronism or other endocrine hypertension, drug-induced hypertension, monogenic hypertension, etc.);
- •Clinically significant laboratory abnormalities at screening: ALT > 1.5 × ULN, AST > 1.5 × ULN, or Serum creatinine ≥ 2.0 mg/dL;
- •Chronic gastrointestinal disorders accompanied by frequent abdominal pain or diarrhea, or history of gastrointestinal surgery that may impair drug absorption;
- •A history of allergic diathesis or hypersensitivity to any component of the investigational product;
- •Pregnant females，or those with a positive pregnancy test at screening, women planning pregnancy during the study, lactating women, or fertile women without adequate contraception protection;
- •Clinically severe and unstable hepatic, renal, hematologic disease, malignant tumor, or unilateral/bilateral renal artery stenosis;
- •Documented psychiatric disorder, or GAD-7 score ≥ 10 or PHQ-9 score ≥ 10;
- •Insomnia due to hyperthyroidism, restless legs syndrome, narcolepsy, sleep-related movement disorders, etc.;
- •Insomnia due to neurodegenerative diseases (Parkinson's disease, Alzheimer's disease, epilepsy, etc.);
- •Acute stroke;
- •Confirmed diagnosis of OSA or STOP-BANG score ≥ 5;
- •Night shift or rotating shift workers;
- •Suspected or confirmed alcohol or drug abuse/dependence;
- •Participation in another clinical trial within 3 months prior to screening; Any other condition deemed by the investigator to render the subject unsuitable for the trial.
结局指标
主要结局
Change from baseline in 24-hour mean systolic blood pressure at Week 12.
时间窗: From baseline to Week 12.
次要结局
- Blood pressure-related parameters(From baseline to Weeks 4, 8, and 12.)
- Other detection parameters(From baseline to Week 12.)
- Other detection parameters(From baseline to Week 12)
- Scale assessments(From baseline to Weeks 4, 8, and 12.)
- Scale assessments(From baseline to Weeks 4, 8, and 12.])
- Polysomnography (PSG, optional)(From baseline to Week 12.)
- 0ther detection parameters(From baseline to Week 12.)
- Blood lipids(From baseline to Week 12.)
研究者
Jing Liu
Director of the Department of Hypertension
Peking University People's Hospital