The Role of Amylin in Bone Metabolism (AmyBone)

Filip Krag Knop

Status: Enrolling

Conditions: Type 1 Diabetes; Bone Diseases, Metabolic

Treatments: Other: Placebo (saline) infusion; Other: Pramlintide

Study type: Interventional

Funder types: Other

Identifiers

NCT06186063

H-22050946

Details and patient eligibility

About

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.

Full 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.

Enrollment: 20 estimated patients

Sex: All

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

---

20 participants in 2 patient groups, including a placebo group

Pramlintide infusion

Experimental group

Description:

A stable amylin analogue.

Treatment:

Other: Pramlintide

Placebo infusion

Placebo Comparator group

Description:

Isotonic saline (0.9% NaCl).

Treatment:

Other: Placebo (saline) infusion