Standard of Care or Weight Loss Drug Therapy in Obesity-related Hypertension - Pilot Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Ambulatory systolic blood pressure
研究概览
简要总结
Hypertension is the leading risk factor for death globally, affecting approximately 30% of adults in the United Kingdom. Obesity is also a serious and ongoing epidemic, with global obesity rates having more than tripled in men and doubled in women, since 1975. In the United Kingdom, 64% of the adult population are overweight or obese. Hypertension and obesity share a well-established association, with obesity being responsible for the development of hypertension in 40-78% of cases. In young adults, this link between body size and blood pressure (BP) is much stronger that in older adults. Since overweight and obesity are among the most common and modifiable causes of high BP, weight loss induced by lifestyle-changes is recommended for overweight or obese patients with hypertension. However, lifestyle interventions, even when successful, result in only moderate weight loss, which is not maintained in the majority of cases. A meta-analysis of randomised controlled trials demonstrated that lifestyle-interventions lead to an average net weight reduction of 5.1 kg, accompanied by a significant, but modest, ~4 mmHg reduction in BP. Weight loss interventions could play a crucial role in the treatment of obesity-related hypertension in young adults.
Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists, originally developed for the treatment of type 2 diabetes, are safe and clinically effective anti-obesity drugs. Recent data show a 10-20% placebo-adjusted reduction in body weight in overweight or obese adults without diabetes using the GLP-1 analogue semaglutide or the dual GLP-1/GIP receptor agonist tirzepatide, with the majority of weight loss achieved within the initial six months. The substantial weight loss induced by these drugs is accompanied by a significant reduction in BP. Two recent meta-analyses showed that semaglutide is associated with a ~5 mmHg placebo-adjusted reduction in clinic systolic BP (SBP). A sub-study of the SURMOUNT-1 trial reported a ~10 mmHg reduction in 24-h ambulatory SBP with tirzepatide. Most participants in these studies were normotensive or had well-controlled hypertension. Furthermore, antihypertensive medication use declined amongst those receiving anti-obesity drugs meaning the BP-lowering effect of weight loss, elicited by these drugs, is probably underestimated. These data suggest that the new anti-obesity drugs could be effective in managing overweight or obesity-related hypertension. Furthermore, it may be possible to cure hypertension in at least some young adults, removing the need for life-long antihypertensive treatment. However, the magnitude and time course of BP reduction elicited by these new anti-obesity drugs remain uncertain.
The primary aim of this feasibility study is to assess the extent and trajectory of BP reduction achieved through intensive weight loss in overweight or obese adults with stage 1 hypertension and compare this to current standard of care measures which uses anti-hypertensive medications and lifestyle advice. The study will utilise a modified trial within cohort approach, using patients based within the clinical pharmacology/hypertension service at Addenbrooke's Hospital, Cambridge.
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
- None
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Eligibility criteria for randomisation
- •Inclusion Criteria:
- •Aged 18 to 40 years (inclusive)
- •Body mass index (BMI) ≥27 kg/m2
- •Clinical diagnosis of primary (essential) hypertension as per NICE guidance
- •Unattended brachial SBP ≥135 and/or DBP ≥85 mmHg and <160/100 mmHg
- •Maximum of one antihypertensive medication
排除标准
- •Anything in medical notes suggesting unsuitable in the opinion of the investigator
- •Eligibility criteria for participation in weight loss arm
- •Inclusion criteria:
- •Written informed consent
- •Aged 18 to 40 years (inclusive)
- •Body mass index ≥27 kg/m2
- •Clinical diagnosis of primary (essential) hypertension as per NICE guidance
- •Unattended brachial SBP ≥135 and/or DBP ≥85 mmHg and <160/100 mmHg
- •Maximum of one antihypertensive medication
- •Exclusion criteria:
- •The presence of any of the following will preclude participant inclusion:
- •Known or suspected secondary hypertension
- •Hypersensitivity to any of the study drugs or excipients
- •Currently taking drugs likely to have interactions with tirzepatide
- •Diagnosis of type 1 or type 2 diabetes mellitus or current usage of insulin or other injectable drugs for the treatment of diabetes such as but not limited to GLP-1 and GIP receptor agonists
- •Prior or planned surgical, endoscopic and/or device-based therapy treatment for obesity
- •Self-reported, intentional or unintentional, change in body weight (over ~10%) within ~three months of screening
- •Known heart failure or clinically significant valvular heart disease
- •Implanted pacemaker or implantable cardioverter defibrillator (ICD)
- •Second or third-degree AV block, sino-atrial block, sick sinus syndrome
- •Known active malignancy including thyroid cancer
- •Known renal impairment (creatinine >150µmol/L)
- •Clinically significant neurological disease
- •History of scleroderma
- •Participants on anticoagulant therapy
- •Known history of pancreatitis
- •Known inflammatory bowel disease
- •History of gallstones (unless previous cholecystectomy)
- •Severe gastroparesis or gastric emptying abnormality
- •Family history of multiple endocrine neoplasia
- •Needle-phobia
- •Planned pregnancy, current pregnancy, or breastfeeding
- •Current involvement in the active treatment phase of other research studies
- •Any other clinical reason which may preclude entry in the opinion of the investigator
研究组 & 干预措施
Tirzepatide [weight loss arm]
6 months of treatment with a combined GLP-1/GIP receptor agonist, tirzepatide
干预措施: Tirzepatide (Drug)
Lifestyle advice and anti-hypertensive medications [standard of Care arm]
干预措施: Anti-Hypertensive medications (Drug)
结局指标
主要结局
Ambulatory systolic blood pressure
时间窗: Baseline to week 24
Change in daytime ambulatory systolic blood pressure in the weight loss arm
次要结局
- Body weight(Change from baseline to week 24 (weight loss arm) and 6 months (standard of care arm))
- Body fat(Change from baseline to week 24 (weight loss arm) and 6 months (standard of care arm))
- Waist:hip ratio(Change from baseline to week 24 (weight loss arm) and 6 months (standard of care arm))
- Cardiac output(At week 24 (weight loss arm) and 6 months (standard of care arm))
- Peripheral vascular resistance(At week 24 (weight loss arm) and 6 months (standard of care arm))
- Pulse wave analysis / pulse wave velocity(At week 24 (weight loss arm) and 6 months (standard of care arm))
- Heart rate variability(At week 24 (weight loss arm) and 6 months (standard of care arm))
- Plasma renin(Change from baseline to week 24 (weight loss arm) and 6 months (standard of care arm))
- Plasma aldosterone(Change from baseline to week 24 (weight loss arm) and 6 months (standard of care arm))
- Plasma metanephrines(Change from baseline to week 24 (weight loss arm) and 6 months (standard of care arm))
- Lipid profile(Change from baseline to week 24 (weight loss arm) and 6 months (standard of care arm))
- HbA1C(Change from baseline to week 24 (weight loss arm) and 6 months (standard of care arm))
- Estimated glomerular filtration rate(Change from baseline to week 24 (weight loss arm) and 6 months (standard of care arm))
- N-terminal pro-B-type natriuretic peptide(Change from baseline to week 24 (weight loss arm) and 6 months (standard of care arm))
- Urine albumin:creatinine ratio(Change from baseline to week 24 (weight loss arm) and 6 months (standard of care arm))
- 24-hour urine sodium(Change from baseline to week 24 (weight loss arm) and 6 months (standard of care arm))
- 24-hour urine aldosterone(Change from baseline to week 24 (weight loss arm) and 6 months (standard of care arm))
- Number of antihypertensive medications(Change from baseline to week 24 (weight loss arm) and 6 months (standard of care arm))
- Quality of life measures(At week 24 (weight loss arm) and 6 months (standard of care arm))
- Ambulatory diastolic blood pressure(Baseline to week 24)
- Clinic systolic blood pressure(Baseline to week 24)
- Clinic diastolic blood pressure(Baseline to week 24)
- Clinic mean arterial pressure(Baseline to week 24)
- Unattended systolic blood pressure(Baseline to week 24)
- Unattended diastolic blood pressure(Baseline to week 24)
- Unattended mean arterial pressure(Baseline to week 24)
- Body weight(Baseline to week 24)
- Body fat(Baseline to week 24)
- Waist:hip ratio(Baseline to week 24)
- Cardiac output(Baseline to week 24)
- Peripheral vascular resistance(Baseline to week 24)
- Pulse wave analysis / pulse wave velocity(Baseline to week 24)
- Heart rate variability(Baseline to week 24)
- Renin(Baseline to week 24)
- Aldosterone(Baseline to week 24)
- Plasma metanephrines(Baseline to week 24)
- Leptin(Baseline to week 24)
- Insulin(Baseline to week 24)
- Lipid profile(Baseline to week 24)
- HbA1C(Baseline to week 24)
- Estimated glomerular filtration rate(Baseline to week 24)
- N-terminal pro-B-type natriuretic peptide(Baseline to week 24)
- Urine albumin:creatinine ratio(Baseline to week 24)
- 24-hour urine sodium(Baseline to week 24)
- 24-hour urine aldosterone(Baseline to week 24)
- Antihypertensive medications(Baseline to week 24)
- Quality of life measures(Baseline to week 24)
- Ambulatory systolic blood pressure(Change from baseline to week 24 (weight loss arm) and 6 months (standard of care arm))
- Ambulatory diastolic blood pressure(Change from baseline to week 24 (weight loss arm) and 6 months (standard of care arm))
- Clinic systolic blood pressure(Change from baseline to week 24 (weight loss arm) and 6 months (standard of care arm))
- Clinic diastolic blood pressure(Change from baseline to week 24 (weight loss arm) and 6 months (standard of care arm))
- Clinic mean arterial pressure(Change from baseline to week 24 (weight loss arm) and 6 months (standard of care arm))
- Unattended systolic blood pressure(Change from baseline to week 24 (weight loss arm) and 6 months (standard of care arm))
- Unattended diastolic blood pressure(Change from baseline to week 24 (weight loss arm) and 6 months (standard of care arm))
- Unattended mean arterial pressure(Change from baseline to week 24 (weight loss arm) and 6 months (standard of care arm))
研究者
James Goodman
Consultant Physician and Clinical Pharmacologist
Cambridge University Hospitals NHS Foundation Trust