Effects of ARA 290, a Non-hematopoietic Erythropoietin Analogue, on Glucose Tolerance, Insulin Secretion, Insulin Sensitivity and Long-term Glucose Control in Individuals With Prediabetes and/or Drug-naive Type 2 Diabetes; a Phase II Study.
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- oral glucose tolerance
研究概览
简要总结
The purpose of this study is to determine whether a non-hematopoietic erythropoietin analogue, ARA 290, exerts beneficial effects on blood glucose levels and insulin secretion in persons with prediabetes (impaired glucose tolerance, IGT, or impaired fasting glucose, IFG), or drug-naive type 2 diabetes.
The study will also evaluate effects of ARA 290 on insulin sensitivity and serum levels of inflammatory agents, e.g. cytokines. In addition, safety will be monitored by following parameters related to hematology, kidney and liver function and lipid levels.
详细描述
Aims of the study:
The primary purpose of this double blind study is to determine in individuals with pre-diabetes (IGT, impaired glucose tolerance; or IFG, impaired fasting glucose) and drug-naïve type 2 diabetes whether ARA 290 reduces disease activity by improving oral glucose tolerance, and insulin secretion, and thereby improves long-term glucose control.
Secondary objectives are to evaluate the effects of ARA 290 on insulin sensitivity; serum levels of inflammatory agents, e.g. cytokine levels; serum levels of gluco-regulatory hormones, such as glucagon-like peptide-1 (GLP-1), glucagon; and safety by registering reported adverse events, and by monitoring clinical chemistry parameters related to hematology, kidney function, liver function and lipid levels.
Study Design:
This is a single-center, randomized, double-blind, placebo-controlled clinical trial to evaluate the effects of ARA 290 on glucose homeostasis in persons with pre-diabetes or early, dietary treated type 2 diabetes. The trial has two parallel arms with 12 subjects in each group, and with a 4-week-intervention period. At screening, a baseline investigation will include a physical examination and the following tests: oral glucose tolerance test (OGTT), and glycosylated hemoglobin (HbA1c).
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Informed consent obtained prior to any trial-related activities
- •Meeting criteria for impaired fasting glucose (IFG), impaired glucose tolerance (IGT), IGF+IFG, or type 2 diabetes at the screening OGTT.
- •IFG = fasting P-glucose 5.6-6.9 mmol/L and 2 hr P-glucose < 7.8 mmol/L; IGT = fasting P-glucose <5.6 mmol/L and 2 hr P-glucose in OGTT 7.8-11.0 mmol/L;diabetes = fasting P-glucose ≥ 7.0 mmol/L and/or 2 hr P-glucose ≥ 11.1 mmol/L.
- •Fasting P-glucose ≤ 9 mmol/L.
- •BMI (body mass index) ≤ 35 kg/m
- •Males aged 40-75 years; women aged 50-75 years and in menopause.
- •Able to read and understand the written consent form, complete study-related procedures, and communicate with the study staff
- •Refrigerator at home for storage of study medication
排除标准
- •Anticipated change in concomitant medication that may interfere with blood glucose homeostasis, such as systemic glucocorticoids, non-selective beta blockers and anabolic steroids.
- •Anti-diabetic (anti-hyperglycemic) medication of any kind.
- •Impaired renal function, defined as S-creatinine ≥ 125 μmol/L for men and ≥ 115 μmol/L for women.
- •Impaired hepatic function defined as plasma alanine aminotransferase (P-ALT) ≥ three times the upper reference limit.
- •Cardiac disease defined as unstable angina pectoris, or myocardial infarction within the last 6 months, or congestive heart failure NYHA (New York Heart Association) class III or IV.
- •Cerebral stroke within the last 6 months.
- •Uncontrolled treated or untreated hypertension (systolic blood pressure ≥ 180 mmHg and/or diastolic blood pressure ≥ 110 mmHg).
- •Cancer diagnosed and/or treated within the last 5 years.
- •Females of childbearing potential.
- •Known or suspected abuse of alcohol or narcotic drugs.
- •Patients should not have received a vaccination or immunization within the month prior to screening
- •The use of Anti-TNF (anti-tumour necrosis factor) therapy or other biological anti-inflammatory agents administered within 3 months prior to screening is not allowed
- •The use of erythropoiesis stimulating agents within the two months prior to screening or during the trial is not allowed.
- •Administration of an investigational drug trial in the 3 months prior to administration of the initial dose of investigational medicinal product or more than 4 times per year.
研究组 & 干预措施
ARA 290
ARA 290, 4.0 mg, injected subcutaneously once every morning during 28 days.
干预措施: ARA 290 (Drug)
Placebo
Placebo, injected subcutaneously once every morning during 28 days,
干预措施: ARA 290 (Drug)
结局指标
主要结局
oral glucose tolerance
时间窗: 28 days
Oral glucose tolerance tests are performed before and after 2 and 4 weeks of treatment. In addition, glucose tolerance will be monitored by checking glycosylated hemoglobin (HbA1c) at the same timepoints, and the participants will perform home blood glucose testing one day every week at home.
Insulin secretion
时间窗: 28 days
Plasma insulin levels will be measured at the oral glucose tolerance tests. In addition, insulin secretion will be assessed by HOMA-beta, using fasting glucose and insulin values.
次要结局
- Inflammation(28 days)
- Insulin sensitivity(28 days)
研究者
Claes-Göran Östenson
Professor
Karolinska Institutet