A Randomised Controlled Trial for People With Established Type 2 Diabetes During Ramadan: Canagliflozin (Invokana™) vs. Standard Dual Therapy Regimen: The 'Can Do Ramadan' Study
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 2
- 主要终点
- HbA1c + weight loss
研究概览
简要总结
This study aims to determine if the addition of Canagliflozin (Invokana™) therapy to monotherapy of metformin is more effective at achieving the double composite endpoint of a reduction in HbA1c (≥ 0.3%) and weight loss (≥1kg) 3-4 weeks post-Ramadan. The study will also include patients currently on dual therapy, specifically metformin plus a sulphonylurea, pioglitazone or repaglinide to determine whether switching to metformin plus Canagliflozin (Invokana™) is more effective at achieving the composite endpoint compared to those remaining on previous dual therapy. There are a number of secondary outcomes including weight loss, rates of hypoglycaemia, blood pressure and a number of biochemical endpoints.
详细描述
There are over one billion Muslims in the world with the majority participating in Ramadan. The prevalence of diabetes in several countries with large Muslim populations is similar to the rates observed in westernised countries, which increases by 10% annually as a result of urbanization and socioeconomic development. Observance of Ramadan is an integral part of Islamic identity being one of the five main pillars that constitute this widely followed religion. Muslims observing Ramadan are required to fast from sunrise to sunset during this holy month. The timing of Ramadan follows the lunar calendar which occurs 10 days earlier each year; this means that the fasting period coincides with the summer season for many consecutive years before moving in line with the winter months. During the summer season Ramadan can take place with the longest hours of daylight which has a greater impact and risk for people with diabetes who fast during this period.
Although the Quran exempts "sick" people from the duty of fasting many Muslims with diabetes do not consider themselves to be sick and are keen to fast. A recent epidemiological study involving 13 Islamic countries reported that 43% of patients with Type 1 diabetes mellitus (T1DM) and 79% of people with type 2 diabetes mellitus (T2DM) fast during this religious period.
Concern for Muslims with diabetes fasting during Ramadan has been recognised by religious leaders and indeed 2009 saw a landmark event. A statement was issued at the meeting of the Council of the International Islamic Fiqh Academy of the Organisation of Islamic Conference at its 19th session. In brief, people with diabetes were classified into four categories in line with expert recommendations published in 2005. Categories 1 and 2 include those with diabetes at very high risk of serious complications and high risk of complications due to fasting, respectively. These two groups are exempt from observing Ramadan. Categories 3 and 4 include those with diabetes who have a medium risk of complications and those with a low risk of complications due to fasting, respectively. The latter two groups are not automatically exempt from observing Ramadan. The risk of complications in this context refers specifically to the likelihood of hypoglycaemic events, and includes other acute illnesses associated with diabetes, patients on renal dialysis, women with diabetes during pregnancy, patients with macrovascular disease, and those who live alone and are on insulin therapy or oral insulin secretagogues. Additionally, all people with T1DM are classed as category 1. However, the impact of the feasting part of Ramadan, for example on hyperglycaemia or deterioration of glycaemic control, is not considered in this statement. Furthermore, it is not known to what extent these guidelines are followed in practice.
There is an abundance of evidence describing the impact of Ramadan on people with T2DM from retrospective to population-based studies. However, there is a lack of evidence available to help guide the management of people with diabetes who wish to observe Ramadan. Fasting and feasting during this holy month can cause health risks for people with diabetes. The Epidemiology of Diabetes and Ramadan 1422/2001 Study ("EPIDAR") was a large population-based, international epidemiological study of diabetes conducted in 13 countries with Muslim populations. One of the aims of this study was to determine the potential effects of fasting in people with diabetes on their well-being and the management of this condition. They observed a 7.5-fold (from 0.4 to 3 events per 100 per month) increased risk of severe hypoglycaemia in patients with T2DM as a result of a change in eating patterns during Ramadan. Severe hypoglycaemia was defined as hypoglycaemia leading to hospitalization. Additionally a 5-fold increase in the incidence of severe hyperglycaemia with/without ketoacidosis was observed in patients with T2DM.
Other risks for people with diabetes who fast during Ramadan include diabetic ketoacidosis due to a lack of insulin, dehydration due to lack of fluid intake during the fasting period, and orthostatic hypotension in addition to an increased risk of thrombosis due to increased blood viscosity secondary to dehydration. Only 62% of those with T2DM in the "EIPDAR" study reported receiving recommendations from their health care providers. These recommendations should include changes in lifestyle (diet and physical activity) and in medication choice and dosage to limit the potential complications of fasting and feasting for this patient population.
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
- 25 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Canagliflozin + Metformin
Canagliflozin + metformin (using the participant's current dose, or dose recommended by the study clinician). An initial dose of 100mg once daily of Canagliflozin will be prescribed, and this will be titrated up to a maximum of 300mg once daily.
干预措施: Canagliflozin (Drug)
Repaglinide + Metformin
Repaglinide + Metformin (using the participant's current dose(s), or dose recommended by the study clinician). An initial dose of 0.5mg once daily where no prior treatment has been given will be prescribed. However, where prior treatment has been in place, an initial dose of 1-2mg once daily will be started and this will be titrated up to a maximum dose of 4mg daily.
干预措施: Repaglinide (Drug)
Pioglitazone + Metformin
Piogliazone + Metformin (using the participant's current dose(s), or dose recommended by the study clinician). For example, Pioglitazone dose will initially be 15mg or 30mg once daily. If the response is inadequate, the maximum daily dosage will be increased to 45mg once daily.
干预措施: Pioglitazone (Drug)
Gliclazide + Metformin
Gliclazide + Metformin (using the participant's current dose(s), or dose recommended by the study clinician). For example, Gliclazide dose will initially be 40-80 mg once daily, up to maximum dose of 160mg twice daily..
干预措施: Gliclazide (Drug)
Glimepiride + Metformin
Glimepiride + Metformin (using the participant's current dose(s), or dose recommended by the study clinician). Glimepiride will initially be administered as 1mg once daily, up to a maximum dose of 4mg once daily.
干预措施: Glimepiride (Drug)
结局指标
主要结局
HbA1c + weight loss
时间窗: Baseline and 3-4 weeks post-Ramadan
Double composite endpoint of a change in HbA1c (≥ 0.3%) and weight loss (≥1kg) between baseline and 3-4 weeks post-Ramadan.
次要结局
- HbA1c + weight loss + Hypoglycaemic events(Baseline and 3-4 weeks post-Ramadan)
- Fructosamine(Baseline and (a) 3-4 weeks post-Ramadan, (b) 12 weeks post-Ramadan and (c) 12 months post-Ramadan.)
- Severe hypoglycaemic events (self-measured)(Baseline and (a) 3-4 weeks post-Ramadan, (b) 12 weeks post-Ramadan and (c) 12 months post-Ramadan.)
- HbA1c(Baseline and (a) 3-4 weeks post-Ramadan, (b) 12 weeks post-Ramadan and (c) 12 months post-Ramadan.)
- LDL cholesterol (mmol/L)(Baseline and (a) 3-4 weeks post-Ramadan, (b) 12 weeks post-Ramadan and (c) 12 months post-Ramadan.)
- Hypoglycaemic events (change) (self-measured)(Baseline and (a) 3-4 weeks post-Ramadan, (b) 12 weeks post-Ramadan and (c) 12 months post-Ramadan.)
- Severe hypoglycaemic events (change) (self-measured)(Baseline and (a) 3-4 weeks post-Ramadan, (b) 12 weeks post-Ramadan and (c) 12 months post-Ramadan.)
- Hypoglycaemic events (self-measured)(Baseline and (a) 3-4 weeks post-Ramadan, (b) 12 weeks post-Ramadan and (c) 12 months post-Ramadan.)
- Hospital admissions(Beginning and end of Ramadan (i.e., during the month of Ramadan))
- Flash Glucose Monitoring - Time in glycaemic range(Baseline and (a) 3-4 weeks post-Ramadan, and (b) during Ramadan.)
- Body weight (kg)(Baseline and (a) 3-4 weeks post-Ramadan, (b) 12 weeks post-Ramadan and (c) 12 months post-Ramadan.)
- Diastolic blood pressure (mm Hg)(Baseline and (a) 3-4 weeks post-Ramadan, (b) 12 weeks post-Ramadan and (c) 12 months post-Ramadan.)
- Systolic blood pressure (mm Hg)(Baseline and (a) 3-4 weeks post-Ramadan, (b) 12 weeks post-Ramadan and (c) 12 months post-Ramadan.)
- HDL cholesterol (mmol/L)(Baseline and (a) 3-4 weeks post-Ramadan, (b) 12 weeks post-Ramadan and (c) 12 months post-Ramadan.)
- Triglycerides (mmol/L)(Baseline and (a) 3-4 weeks post-Ramadan, (b) 12 weeks post-Ramadan and (c) 12 months post-Ramadan.)
- Diabetes Treatment Satisfaction(Baseline and (a) 3-4 weeks post-Ramadan, (b) 12 weeks post-Ramadan and (c) 12 months post-Ramadan.)
- No weight gain (kg) + severe hypoglycaemic events(Baseline and (a) 3-4 weeks post-Ramadan, (b) 12 weeks post-Ramadan and (c) 12 months post-Ramadan.)
- No weight gain (kg) + no hypoglycaemic events(Baseline and (a) 3-4 weeks post-Ramadan, (b) 12 weeks post-Ramadan and (c) 12 months post-Ramadan.)
- Total cholesterol (mmol/L)(Baseline and (a) 3-4 weeks post-Ramadan, (b) 12 weeks post-Ramadan and (c) 12 months post-Ramadan.)
- Physical Activity (self-reported)(Baseline and (a) 3-4 weeks post-Ramadan, (b) 12 weeks post-Ramadan and (c) 12 months post-Ramadan.)
- Hypoglycaemic events (per person year) (self-measured)(Baseline and (a) 3-4 weeks post-Ramadan, (b) 12 weeks post-Ramadan and (c) 12 months post-Ramadan.)
- Severe hypoglycaemic events (per person year) (self-measured)(Baseline and (a) 3-4 weeks post-Ramadan, (b) 12 weeks post-Ramadan and (c) 12 months post-Ramadan.)
- Flash Glucose Monitoring - Incidence(Baseline and (a) 3-4 weeks post-Ramadan, and (b) during Ramadan.)
- Flash Glucose Monitoring - Change(Baseline and (a) 3-4 weeks post-Ramadan, and (b) during Ramadan.)
- Flash Glucose Monitoring - MAGE(Baseline and (a) 3-4 weeks post-Ramadan, and (b) during Ramadan.)
- Physical Activity (GENEActiv)(Baseline and (a) 3-4 weeks post-Ramadan, (b) 12 weeks post-Ramadan and (c) 12 months post-Ramadan.)
- Weight loss (kg) + severe hypoglycaemic events(Baseline and (a) 3-4 weeks post-Ramadan, (b) 12 weeks post-Ramadan and (c) 12 months post-Ramadan.)
- No weight gain (kg) + reduction of hypoglycaemic events(Baseline and (a) 3-4 weeks post-Ramadan, (b) 12 weeks post-Ramadan and (c) 12 months post-Ramadan.)
- HbA1c (%) + severe hypoglycaemic events(Baseline and (a) 3-4 weeks post-Ramadan, (b) 12 weeks post-Ramadan and (c) 12 months post-Ramadan.)
- HbA1c (%) + hypoglycaemic events(Baseline and (a) 3-4 weeks post-Ramadan, (b) 12 weeks post-Ramadan and (c) 12 months post-Ramadan.)
- No weight gain (kg) + HbA1c (%)(Baseline and (a) 3-4 weeks post-Ramadan, (b) 12 weeks post-Ramadan and (c) 12 months post-Ramadan.)