The Role of Amylin in Bone Metabolism (AmyBone)

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.

Study Overview

• Status: Recruiting
• Conditions: Type 1 Diabetes; Bone Diseases, Metabolic
• Intervention / Treatment: Other: Pramlintide; Other: Placebo (saline) infusion

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.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mathilde K. Preskou, MD; Phone Number: +45 2349 6823; Email: emma.mathilde.kirsmeier.preskou.01@regionh.dk

Study Locations

• Denmark
  • Capital Region
    • Hellerup, Capital Region, Denmark, 2900
      • Recruiting
      • Center for Clinical Metabolic Research, Gentofte Hospital
      • Contact: Filip K. Knop, Professor, MD, PhD; Email: filip.krag.knop.01@regionh.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pramlintide infusion; A stable amylin analogue.	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 Comparator: Placebo infusion; Isotonic saline (0.9% NaCl).	Other: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Filip Krag Knop
• Investigators: Principal Investigator: Filip K. Knop, Professor, MD, PhD, Center for Clinical Metabolic Research, Gentofte Hospital, Denmark

Study record dates

Study Major Dates

• Study Start (Actual): February 12, 2024
• Primary Completion (Estimated): August 1, 2024
• Study Completion (Estimated): August 1, 2024

Study Registration Dates

• First Submitted: December 15, 2023
• First Submitted That Met QC Criteria: December 15, 2023
• First Posted (Actual): December 29, 2023

Study Record Updates

• Last Update Posted (Estimated): February 21, 2024
• Last Update Submitted That Met QC Criteria: February 16, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Metabolic; Metabolic Diseases; Hypoglycemic Agents; Physiological Effects of Drugs; Pramlintide
• Other Study ID Numbers: H-22050946

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No