The Role of Amylin in Bone Metabolism
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Relative changes in the plasma levels of N-terminal propeptide of type I procollagen (P1NP)
研究概览
简要总结
The clinical study aims to investigate the effect of the intravenously administrated amylin analogue (pramlintide) on the circulating levels of C-terminal telopeptide of type I collagen (CTX-1) (a marker of bone resorption) and N-terminal propeptide of type I procollagen (P1NP) (a marker of bone formation) in individuals with type 1 diabetes and matched healthy controls during fasting euglycemic conditions.
详细描述
Using a randomised double blinded placebo-controlled crossover design the investigators will evaluate the effects of the intravenously administrated amylin analogue (pramlintide) on circulating levels of CTX-1 and P1NP in ten individuals with type 1 diabetes and ten healthy controls matched for age, gender and body mass index (BMI) during fasting and euglycemic conditions. Each participant will receive double-blinded infusions of pramlintide (3 pmol/kg/min) and saline on two separate study days performed in randomised order.
The primary endpoints are the relative changes in the plasma levels of P1NP and CTX-1. The changes in plasma concentrations will be assessed by the total and incremental (baseline-subtracted) area under the curve for plasma CTX-1 and P1NP as well as %-changes from baseline including nadir.
The secondary endpoints encompass changes in plasma concentrations of calcium, parathyroid hormone (PTH), alkaline phosphatase, osteocalcin, glucagon, insulin, C-peptide, glucose, glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 and glucagon-like peptide 2.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •type 1 diabetes:
- •Caucasian ethnicity
- •Age between 18 and 60 years
- •BMI between 18.5 and 27 kg/m2
- •Type 1 diabetes (diagnosed according to the criteria of the World Health Organization) with HbA1c <69 mmol/mol (<8.5%) and
- •Type 1 diabetes duration of 2-20 years
- •C-peptide negative (stimulated C-peptide ≤30 pmol/l)
- •Treatment with a stable basal-bolus or insulin pump regimen for ≥3 months
- •Normal vitamin D (>50 nmol/l)
- •Informed consent
排除标准
- •type 1 diabetes:
- •Anaemia (haemoglobin below normal range)
- •Liver disease (ALAT and/or ASAT >2 times normal values) or history of hepatobiliary disorder
- •Nephropathy (eGFR <60 ml/min/1,73m2 and/or microalbuminuria)
- •Microvascular complications except non-proliferative retinopathy
- •Treatment with anti-osteoporosis medication or glucocorticoids
- •Fractures within the last 6 months
- •For women: currently perimenopausal or postmenopausal
- •Diseases affecting calcium metabolism (e.g. hypoparathyroidism, hyperparathyroidism, osteoporosis, vitamin D deficiency and cancer)
- •Pregnancy or breastfeeding
- •Any physical or psychological condition that the investigator feels would interfere with trial participation
- •Treatment with any glucose-lowering drugs beside insulin, treatment with medication against osteoporosis or treatment with any form of glucocorticoids
- •Inclusion criteria healthy controls:
- •Caucasian ethnicity
- •Age between 18 and 60 years
- •BMI between 18.5 and 27 kg/m2
- •Fasting plasma glucose ≤7.0 mmol/l and glycated haemoglobin (HbA1c) <48 mmol/mol
- •Normal blood haemoglobin (8.3-10.5 mmol/l (males) and 7.3 - 9.5 mmol/l (females))
- •Normal plasma vitamin D (>50 nmol/l)
- •Informed consent
- •Exclusion criteria healthy controls:
- •Any form of diabetes (according to World Health Organization criteria)
- •Anaemia (haemoglobin below normal range)
- •Nephropathy (eGFR <60 ml/min/1,73m2 and/or microalbuminuria)
- •Known liver disease and/or alanine transaminase (ALAT) or aspartate transaminase (ASAT) >2 × upper normal limit
- •Any fractures within the last 6 months
- •For women: currently perimenopausal or postmenopausal
- •Diseases affecting calcium metabolism (e.g. hypoparathyroidism, hyperparathyroidism, osteoporosis, vitamin D deficiency and cancer)
- •Pregnancy or breastfeeding
- •Any condition considered incompatible with participation by the investigators
研究组 & 干预措施
Placebo infusion
Isotonic saline (0.9% NaCl).
干预措施: Placebo (saline) infusion (Other)
结局指标
主要结局
Relative changes in the plasma levels of N-terminal propeptide of type I procollagen (P1NP)
时间窗: From -15 minutes to 180 minutes
The changes in plasma concentrations will be assessed by the total and incremental (baseline-subtracted) area under the curve for plasma P1NP as well as %-changes from baseline including nadir.
Relative changes in the plasma levels of C-terminal telopeptide of type I collagen (CTX-1)
时间窗: From -15 minutes to 180 minutes
The changes in plasma concentrations will be assessed by the total and incremental (baseline-subtracted) area under the curve for plasma CTX-1 as well as %-changes from baseline including nadir.
次要结局
- Changes in plasma concentrations of C-peptide.(From -15 minutes to 180 minutes)
- Changes in plasma concentrations of glucagon.(From -15 minutes to 180 minutes)
- Changes in plasma concentrations of insulin.(From -15 minutes to 180 minutes)
- Changes in plasma concentrations of glucose-dependent insulinotropic polypeptide (GIP).(From -15 minutes to 180 minutes)
- Changes in plasma concentrations of calcium.(From -15 minutes to 180 minutes)
- Changes in plasma concentrations of glucose.(From -15 minutes to 180 minutes)
- Changes in plasma concentrations of glucagon-like peptide 1 (GLP-1).(From -15 minutes to 180 minutes)
- Changes in plasma concentrations of glucagon-like peptide 2 (GLP-2).(From -15 minutes to 180 minutes)
- Changes in plasma concentrations of parathyroid hormone (PTH)(From -15 minutes to 180 minutes)
- Changes in plasma concentrations of alkaline phosphatase(From -15 minutes to 180 minutes)
- Changes in plasma concentrations of osteocalcin(From -15 minutes to 180 minutes)
研究者
Filip Krag Knop
Professor, MD, PhD
University Hospital, Gentofte, Copenhagen