Bone Diseases, Metabolic, Type 1 Diabetes
Conditions
Brief summary
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.
Detailed description
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.
Interventions
OTHERPramlintide
At time 0 min, continuous infusion of a stable amylin analogue (pramlintide) will be initiated at a rate of 3.0 pmol/kg/min. The infusion will be terminated after 180 minutes.
OTHERPlacebo (saline) infusion
At time 0 min, continuous infusion of isotonic saline will be initiated at a rate of 150 ml/h. The infusion will be terminated after 180 minutes.
Sponsors
Filip Krag Knop
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Intervention model description
The investigators apply a randomized, double-blinded, placebo-controlled, crossover design.
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
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
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relative changes in the plasma levels of C-terminal telopeptide of type I collagen (CTX-1) | 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. |
| Relative changes in the plasma levels of N-terminal propeptide of type I procollagen (P1NP) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in plasma concentrations of C-peptide. | 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 levels as well as %-changes from baseline including nadir. |
| Changes in plasma concentrations of glucose. | 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 levels as well as %-changes from baseline including nadir. |
| Changes in plasma concentrations of glucose-dependent insulinotropic polypeptide (GIP). | 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 levels as well as %-changes from baseline including nadir. |
| Changes in plasma concentrations of glucagon-like peptide 1 (GLP-1). | 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 levels as well as %-changes from baseline including nadir. |
| Changes in plasma concentrations of glucagon. | 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 levels as well as %-changes from baseline including nadir. |
| Changes in plasma concentrations of calcium. | 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 levels as well as %-changes from baseline including nadir. |
| Changes in plasma concentrations of parathyroid hormone (PTH) | 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 levels as well as %-changes from baseline including nadir. |
| Changes in plasma concentrations of alkaline phosphatase | 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 levels as well as %-changes from baseline including nadir. |
| Changes in plasma concentrations of osteocalcin | 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 levels as well as %-changes from baseline including nadir. |
| Changes in plasma concentrations of glucagon-like peptide 2 (GLP-2). | 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 levels as well as %-changes from baseline including nadir. |
| Changes in plasma concentrations of insulin. | 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 levels as well as %-changes from baseline including nadir. |
Countries
Denmark
Contacts
Primary ContactMathilde K. Preskou, MD
Outcome results
None listed