Diabetes Diagnosis, Management, Prevention and Education in Guinea-Bissau
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- F-glucose
研究概览
简要总结
Type 2 diabetes (T2D) will affect ~650 million adults worldwide by 2040 and about as many will have pre-diabetes. Chronic hyperinsulinemia/insulin resistance precedes T2D development. Studies link insulin resistance with chronic inflammation and oxidative stress.
In Guinea-Bissau, a low-income country in West Africa, the T2D incidence is largely unknown and there is an acute lack of diabetes doctors, nurses and other diabetes educators. They hardly have access to insulin, and mortality from T2D complications is high. Previous studies by the Bandim Health Project (www.bandim.org) in the country show that the Bacillus Calmette-Guérin (BCG) vaccine has non-specific effects, well beyond tuberculosis prevention, conferring a general protection against unrelated pathogens. At the same time, studies from the US have also shown that BCG can significantly improve glycemic control in Type-1 diabetes (T1D) patients. Yet, no such studies have been done in T2D or pre-diabetes.
The purpose of the present study is to administer BCG to patients with pre-diabetes, in order to reduce hyperinsulinemia/chronic inflammation, a novel strategy to flatten the growing T2D incidence.
详细描述
BACKGROUND The lack of medical infrastructure and health education is clear across Guinea-Bissau, West Africa. Besides pilot studies from the capital Bissau, showing poor glycemic control and high mortality, due mainly to untreated type 2 diabetes (T2D), the diabetes prevalence is largely unknown. Patients cannot easily afford treatment, including insulin. Better health education, cheaper prevention and treatment strategies are needed.
Importantly, data show that the Bacillus Calmette Guerin (BCG) vaccine has key non-specific health effects, well beyond prevention of the target disease tuberculosis. Furthermore, in the US, it has been shown that BCG revaccination lowers haemoglobin-A1c (HbA1c) in people with Type-1 diabetes (T1D). Yet, no such studies have been done in T2D subjects.
The exact pathways of the non-specific effects of BCG are still being exploried, but it may be due to an increase in basal systemic levels of type 1 cytokines and immune cells and induction of epigenetic modifications in the innate immune cells, leading to increased pro-inflammatory responses towards unrelated pathogens. These modifications are accompanied by changes in glucose metabolism, increasing aerobic glycolysis, a state of high glucose utilization. In the randomized trial from the US in T1D patients, BCG lowered HbA1c close to normal levels. A systemic shift in glucose metabolism from oxidative phosphorylation to aerobic glycolysis was observed. BCG vaccination could therefore potentially be a cheap and safe tool to prevent T2D in resource-limited settings.
In Guinea-Bissau, only a couple of diabetes studies have been performed in patients with tuberculosis, HIV, twins and at a local diabetes clinic. Recently, study identified a severe lack of diabetes prevention, management and education. BCG vaccination could thus be a very valuable tool to prevent (and possibly treat) diabetes in low-income countries like Guinea-Bissau.
At the same time, studies indicate that long-term inflammation may predict dysmetabolism, independent of being lean or obese. Chronic inflammation is an important feature of insulin resistance and T2D, in which specific pro-inflammatory cytokines drive disease.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Outcomes Assessor)
盲法说明
Participants will be blinded to treatment. The investigators (or delegated vaccinator, e.g. nurse) administering the BCG vaccine or placebo (saline) will not be blinded. In case of serious adverse events, the participant can be unblinded after consultation with the coordinating PI.
入排标准
- 年龄范围
- 18 Years 至 64 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •for BCG trial:
- •Ages 18-64
- •Planning to continue living in the study area
- •F-glucose from 5.6-6.9 mmol/L and HbA1c between 39-47mmol/mol.
排除标准
- •for BCG trial:
- •HIV infection (an HIV test to be done before enrolment)
- •Pregnancy (a pregnancy test to be done before enrolment in women in the childbearing age)
- •Chemotherapy
研究组 & 干预措施
BCG vaccine
Participants that are randomized in the active arm will receive an adult 0.1 ml dose of BCG vaccine (e.g. BCG-Denmark or BCG-Japan) in the skin covering the left upper deltoid muscle. Two doses will be given, 4 weeks apart.
Intervention: Biological BCG-vaccine.
干预措施: BCG vaccine (two doses, 4 weeks apart) (Biological)
Placebo
Placebo will be 0.1 ml sterile 0.9 % NaCl, which has a similar color as the resuspended BCG vaccine. Two placebo doses will be given, 4 weeks apart.
干预措施: Saline placebo (Two doses, 4 weeks apart) (Biological)
结局指标
主要结局
F-glucose
时间窗: 3 years after enrolment
F-glucose levels at the end of the study period in people with pre-diabetes
Hba1c
时间窗: 3 years after enrolment
Hba1c levels at the end of the study period in people with pre-diabetes
次要结局
- Type-2 diabetes(3 years after enrolment)
- Time to Type-2 diabetes development(0-3 years after enrolment)