The Role of Amylin in Bone Metabolism

Type 1 Diabetes Clinical Trial

— AmyBone  

Official title:

The Role of Amylin in Bone Metabolism

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06186063
• Other study ID #: H-22050946
• Status: Recruiting
• Phase: N/A
• Start date: February 12, 2024
• Est. completion date: August 1, 2024

Study information

• Verified date: February 2024
• Source: University Hospital, Gentofte, Copenhagen
• Contact: Mathilde K. Preskou, MD
• Phone: +45 2349 6823
• Email: emma.mathilde.kirsmeier.preskou.01[@]regionh.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: August 1, 2024
• Est. primary completion date: August 1, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Bone Diseases
• Bone Diseases, Metabolic
• Metabolic Diseases
• Type 1 Diabetes

Intervention

Other:
• Pramlintide
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.
• Placebo (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.

Locations

Country	Name	City	State
Denmark	Center for Clinical Metabolic Research, Gentofte Hospital	Hellerup	Capital Region

Sponsors (1)

Lead Sponsor	Collaborator
Filip Krag Knop

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Relative changes in the plasma levels of C-terminal telopeptide of type I collagen (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 as well as %-changes from baseline including nadir.	From -15 minutes to 180 minutes
Primary	Relative changes in the plasma levels of N-terminal propeptide of type I procollagen (P1NP)	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.	From -15 minutes to 180 minutes
Secondary	Changes in plasma concentrations of glucagon.	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.	From -15 minutes to 180 minutes
Secondary	Changes in plasma concentrations of insulin.	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.	From -15 minutes to 180 minutes
Secondary	Changes in plasma concentrations of C-peptide.	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.	From -15 minutes to 180 minutes
Secondary	Changes in plasma concentrations of glucose.	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.	From -15 minutes to 180 minutes
Secondary	Changes in plasma concentrations of glucose-dependent insulinotropic polypeptide (GIP).	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.	From -15 minutes to 180 minutes
Secondary	Changes in plasma concentrations of glucagon-like peptide 1 (GLP-1).	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.	From -15 minutes to 180 minutes
Secondary	Changes in plasma concentrations of glucagon-like peptide 2 (GLP-2).	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.	From -15 minutes to 180 minutes
Secondary	Changes in plasma concentrations of calcium.	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.	From -15 minutes to 180 minutes
Secondary	Changes in plasma concentrations of parathyroid hormone (PTH)	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.	From -15 minutes to 180 minutes
Secondary	Changes in plasma concentrations of alkaline phosphatase	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.	From -15 minutes to 180 minutes
Secondary	Changes in plasma concentrations of osteocalcin	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.	From -15 minutes to 180 minutes