The Effect of Simvastatin on Bone Density in Postmenopausal Women With Type 2 Diabetes: a Double-blind, Randomized Active-comparator (Ezetimibe) Controlled Clinical Trial
试验速览
- 阶段
- 4 期
- 状态
- Enrolling By Invitation
- 入组人数
- 240
- 试验地点
- 1
- 主要终点
- The change in the TH BMD after 18 months of simvastatin compared with ezetimibe
研究概览
简要总结
This study aims to evaluate the impact of simvastatin on the bone density of postmenopausal women with type 2 diabetes over a duration of 18 months, using a randomized controlled trial design. Aiming to recruit 240 patients, half of them will be randomly assigned to receive simvastatin treatment, while the other half will receive ezetimibe, also a lipid-lowering agent with no known effect on bone. Bone density will be measured at the baseline and the end of the study for comparison of the changes between the simvastatin and the ezetimibe groups.
This is an investigator-initiated study. The principal investigator and the study team will be responsible for ensuring that the study is conducted in compliance with this protocol and the study data collected are verified against the relevant source documents.
All participants will undergo clinical and biochemical assessments at baseline of the trial. Participants will be seen by an endocrinologist at baseline and subsequent follow-up visits at 3, 6, 12 and 18 months respectively.
详细描述
Study Procedures and Assessments Screening Procedures
Patients will be recruited from medical out-patient clinics, mainly from the primary health care clinics, in the Hong Kong West Cluster of the Hong Kong Hospital Authority. Consecutive participants who fulfil the inclusion and exclusion criteria are invited to participate in this randomized controlled trial after obtaining informed consent.
Clinical and biochemical assessments
Participants will attend a clinical assessment session at baseline after an overnight fast for at least 8 hours. Demographic data and medical history will be obtained using a standardized questionnaire. Personal and family history of fragility fractures (spine, hip, humerus, wrist and ankle) will be recorded. Important clinical risk factors of osteoporosis will be evaluated, including smoking, drinking, family history of fragility fractures, parental history of hip fractures, prior use and duration of hormonal replacement therapy, and levels of physical activity. The levels of physical activity will be assessed through the International Physical Activity Questionnaire (IPAQ). Daily calcium intake will be assessed using a semi-quantitative questionnaire. Body weight, body height and blood pressure (BP) will be measured. Hypertension is defined as BP ≥140/90 mmHg or the use of antihypertensive medications.
Fasting blood will be drawn for plasma glucose, HbA1c, insulin, lipid profile, albumin, calcium, phosphate, creatinine levels and eGFR. Patients with 25OHD levels <50 nmol/L will be given additional cholecalciferol 1000 units/day for 8 weeks followed by reassessment of 25-hydroxyvitamin D (25OHD) to ensure repletion.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Health Services Research
- 盲法
- Double (Participant, Investigator)
盲法说明
The computer-generated sequence will be supplied by the study statistician, independent of the investigators. To facilitate double-blinding, placebo tablets with the same shapes as simvastatin 10mg and ezetimibe 10mg, respectively.
入排标准
- 年龄范围
- 50 Years 至 74 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Chinese women
- •Aged 50 to 74 years (inclusive);
- •Type 2 diabetes Mellitus;
- •Postmenopausal: confirmed with the last menstrual period >12 months by the time of recruitment into the study
排除标准
- •Entry HbA1c >8.5%;
- •On thiazolidinedione;
- •Baseline LDL-cholesterol >3.0 mmol/L, triglyceride >5.0 mmol/L, or known familial hypercholesterolaemia;
- •History of hip and/or clinical vertebral fractures;
- •Osteoporosis by BMD criteria on DXA;
- •On anti-osteoporosis therapy within the prior 2 years;
- •Evidence of secondary causes of osteoporosis including Cushing's syndrome, acromegaly, thyrotoxicosis, primary hyperparathyroidism, metabolic bone diseases (e.g. osteomalacia), and systemic glucocorticoid treatment;
- •Evidence of documented ASCVD, which includes previous acute coronary syndrome, stable angina, coronary revascularization, stroke and transient ischaemic attack and peripheral arterial disease;
- •On lipid-lowering therapy within the prior 2 years;
- •Known contraindications to statin therapy including allergy, intolerance and significant liver function abnormality (alanine aminotransferase level >3 times upper limit of normal);
- •Significant diabetic complication(s): pre-proliferative / proliferative diabetic retinopathy, diabetic maculopathy, overt proteinuria, estimated glomerular filtration rate (eGFR) <30 mL/min;
- •Inability to give an informed consent
研究组 & 干预措施
Simvastatin 10mg/day
One simvastatin 10mg-tablet and one placebo tablet with the shape of ezetimibe 10mg each day.
干预措施: Simvastatin 10mg (Drug)
Ezetimibe 10mg/day
One ezetimibe 10mg-tablet and one placebo tablet with the shape of simvastatin 10mg each day.
干预措施: Ezetimibe 10mg (Drug)
结局指标
主要结局
The change in the TH BMD after 18 months of simvastatin compared with ezetimibe
时间窗: Screening visit and Visit 5 (18 month after baseline visit)
BMD at the TH will be measured with DXA and compared.
次要结局
- The changes in the FN BMD after 18 months of simvastatin compared with ezetimibe(Screening visit and Visit 5 (18 month after baseline visit))
- The changes in bone turnover marker, carboxy-terminal cross-linked telopeptide of type 1 collagen (CTX) after 6 months and 18 months of simvastatin compared with ezetimibe(Baseline visit, Visit 3 (6 months after Baseline visit) and Visit 5 (18 months after Baseline visit))
- The changes in the LS BMD after 18 months of simvastatin compared with ezetimibe(Screening visit and Visit 5 (18 month after baseline visit))
- The changes in BMD over distal radius after 18 months of simvastatin compared with ezetimibe(Screening visit and Visit 5 (18 month after baseline visit))
- The changes in bone turnover marker, amino-terminal propeptides of type 1 collagen (P1NP) after 6 months and 18 months of simvastatin compared with ezetimibe(Baseline visit, Visit 3 (6 months after Baseline visit) and Visit 5 (18 months after Baseline visit))
- The changes in TBS after 18 months of simvastatin compared with ezetimibe(Screening visit and Visit 5 (18 month after baseline visit))
研究者
Dr. Lui Tak Wai David
Clinical Assistant Professor
The University of Hong Kong