Clinical trial NCT06186063: The Role of Amylin in Bone Metabolism
Official title: The Role of Amylin in Bone Metabolism
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Bone Diseases, Metabolic
Type 1 Diabetes
Lead sponsor: University Hospital, Gentofte, Copenhagen
Sponsor class: OTHER
First posted: 2023-12-29
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: The investigators apply a randomized, double-blinded, placebo-controlled, crossover design.
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

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

Primary outcomes:
measure: Relative changes in the plasma levels of C-terminal telopeptide of type I collagen (CTX-1)
timeFrame: From -15 minutes to 180 minutes
measure: Relative changes in the plasma levels of N-terminal propeptide of type I procollagen (P1NP)
timeFrame: From -15 minutes to 180 minutes
Secondary outcomes:
measure: Changes in plasma concentrations of glucagon.
timeFrame: From -15 minutes to 180 minutes
measure: Changes in plasma concentrations of insulin.
timeFrame: From -15 minutes to 180 minutes
measure: Changes in plasma concentrations of C-peptide.
timeFrame: From -15 minutes to 180 minutes
measure: Changes in plasma concentrations of glucose.
timeFrame: From -15 minutes to 180 minutes
measure: Changes in plasma concentrations of glucose-dependent insulinotropic polypeptide (GIP).
timeFrame: From -15 minutes to 180 minutes
measure: Changes in plasma concentrations of glucagon-like peptide 1 (GLP-1).
timeFrame: From -15 minutes to 180 minutes
measure: Changes in plasma concentrations of glucagon-like peptide 2 (GLP-2).
timeFrame: From -15 minutes to 180 minutes
measure: Changes in plasma concentrations of calcium.
timeFrame: From -15 minutes to 180 minutes
measure: Changes in plasma concentrations of parathyroid hormone (PTH)
timeFrame: From -15 minutes to 180 minutes
measure: Changes in plasma concentrations of alkaline phosphatase
timeFrame: From -15 minutes to 180 minutes
measure: Changes in plasma concentrations of osteocalcin
timeFrame: From -15 minutes to 180 minutes
Other outcomes:
Locations:
city: Hellerup
country: Denmark
facility: Center for Clinical Metabolic Research, Gentofte Hospital
state: Capital Region
Study officials:
affiliation: Center for Clinical Metabolic Research, Gentofte Hospital, Denmark
name: Filip K. Knop, Professor, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: