Effect of Anti-diabetic Drugs on Bone Metabolism and Glycemic Variability (BoneGlyc)

• ClinicalTrials.gov Identifier: NCT01679899
• Recruitment Status: Completed
• First Posted: September 6, 2012
• Last Update Posted: November 4, 2016
• Sponsor: Centro de Diabetes Curitiba Ltda
• Information provided by (Responsible Party): Centro de Diabetes Curitiba Ltda

Study Description

Brief Summary:

This is a Monocentric, Prospective, Randomized, Open-label, Comparative, Phase IV Study, to compare the effects of Vildagliptin and Gliclazide MR on Markers of Bone Remodeling, Bone Mineral Density and Glycemic Variability in Postmenopausal Women with Type 2 Diabetes.

A total of 38 women with documented Type 2 Diabetes and menopause will be enrolled. The active treatment will include a 50 mg dose of vildagliptin OD twice a day. As comparator, gliclazide MR will be administered at a dose of 60 to 120 mg OD once a day.

Condition or disease	Intervention/treatment	Phase
Type 2 Diabetes Mellitus; Menopause; Osteoporosis; Osteopenia	Drug: Vildagliptin; Drug: Gliclazide MR	Phase 4

Detailed Description:

This is a Monocentric, Prospective, Randomized, Open-label, Comparative, Phase IV Study, to compare the effects of Vildagliptin and Gliclazide MR on Markers of Bone Remodeling, Bone Mineral Density and Glycemic Variability in Postmenopausal Women with Type 2 Diabetes.

Target population of clinical trial subjects A total of 38 women with documented Type 2 Diabetes and menopause will be enrolled. To be as close to a real life scenario as possible, clinical trial subjects which are treated with glucose-lowering medication (except incretin or sulfonylurea based therapies) and treatment-naive subjects will be included.

Investigational Product, posology and method of administration The active treatment will include a 50 mg dose of vildagliptin OD twice a day.

Comparator, posology and method of administration As comparator, gliclazide MR will be administered at a dose of 60 to 120 mg OD once a day.

Treatment duration The study will have an expected total duration of 18 months, 12 months of active treatment.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 56 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Effect of Anti-diabetic Drugs on Bone Metabolism and Glycemic Variability.A Comparison Between Vildagliptin and Gliclazide MR
• Study Start Date: December 2012
• Actual Primary Completion Date: October 2015
• Actual Study Completion Date: October 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: Vildagliptin; Vildagliptin 50 mg bid for 12 months	Drug: Vildagliptin; Vildagliptin 50mg bid orally for 12 months; Other Name: Galvus
Active Comparator: Gliclazide MR; Gliclazide MR 60 or 120mg once a day for 12 months	Drug: Gliclazide MR; Gliclazide MR 60 or 120mg orally for 12 months; Other Name: Diamicron MR

Outcome Measures

Primary Outcome Measures :

1. Markers of bone remodeling [ Time Frame: 6 months ]

   Primary outcome is to compare the effect of vildagliptin with gliclazide MR on markers of bone remodeling. The outcome variables are the blood levels of:

   1. Osteocalcin (OC)
   2. Bone-specific alkaline phosphatase (BALP)
   3. Carboxy-terminal telopeptide of type I collagen (CTX)
   4. Amino-terminal telopeptide of type I collagen (NTX)

Secondary Outcome Measures :

1. Bone mineral density of lumbar spine and femur by X-ray absorptiometry [ Time Frame: 12 months ]
   To compare the effect of vildagliptin with gliclazide MR on bone mineral density of lumbar spine and femur by X-ray absorptiometry after 12-month treatment.
2. Glycemic variability [ Time Frame: 6 months ]
   To compare the effect of vildagliptin with gliclazide MR on glycemic variability measured by MAGE method (mean amplitude of glycemic excursion) using a continuous glucose monitoring system
3. Calcitonin [ Time Frame: 12 months ]
   Dosage of serum calcitonin

Other Outcome Measures:

1. Levels of aminotransferases [ Time Frame: 6 months ]
   Dosage of alanine aminotransferase (ALT, SGOT) and aspartate aminotransferase (AST, SGPT)

Eligibility Criteria

• Ages Eligible for Study: 40 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Informed consent form obtained before any study-related activity. Study-related activities are any procedure that would not be performed during the normal treatment of the patient.

• All study subjects must be women diagnosed with type 2 diabetes based on current guidelines of Sociedade Brasileira de Diabetes (SBD - Brazilian Society of Diabetes) and/or American Society of Diabetes (ADA) and they should have all the following criteria:

  • Age ≥ 40 years old.
  • HbA1c ≥ 6.5% at randomization.
• Menopause defined as:
• Absence of menstruation for at least 12 months in patients with an intact uterus, or
• FSH level greater than 30 mIU/mL in a hysterectomized patient and/or,
• FSH level greater than 30 mIU/mL in a patient with surgical menopause.

Exclusion Criteria:

• Acute vascular event (cardiac, cerebral or peripheral) for at least 2 months of randomization.
• Patient on chronic dialysis and/or renal transplantation and/or serum creatinine > 1.5 mg/dL.
• Patients with HIV, severe autoimmune disease or chronic treatment with oral steroids (> 30 consecutive days).
• Current or previous treatment (within 6 months) with incretin (DPP-IV inhibitor or GLP-1 analog) within 6 months prior to randomization.
• Current or previous treatment with pioglitazone or rosiglitazone within 12 months prior to randomization.
• Sustained arterial hypertension > 180/100 mm Hg.
• Body mass index (BMI) > 50 kg/m².
• HbA1c ≥ 9,5% at randomization.
• Transaminases (AST (SGOT) and ALT (SGPT)) > 2.5 x upper limit of normal.
• Chronic liver disease or alcoholic liver disease.
• LDL-cholesterol > 250 mg/dL (> 6.48 mmol/L).
• Triglycerides > 1000 mg/dL (> 11.3 mmol/L).
• HDL-cholesterol < 25 mg/dL (< 0.64 mmol/L).
• Levels of 25-OH-vitamin D < 20ng/mL at randomization
• Abnormal levels of PTH, cortisol, IGF-1 or GH at randomization
• Prescription of any investigational medication within one year before the screening visit (visit 1), unless there is a direct benefit to the study subject, at the discretion of the investigator.
• History of previous fracture
• Pregnant or breastfeeding patients.
• Previous participation on this study.
• Individuals at risk for poor adherence to the protocol or medication.
• Any condition that makes the patient unable to complete the study within 12 months.

Contacts and Locations

Locations

Brazil

Centro de Diabetes Curitiba

Curitiba, Parana, Brazil, 80810040

Sponsors and Collaborators

Centro de Diabetes Curitiba Ltda

Investigators

• Study Chair: Andre GD Vianna, MD; Centro de Diabetes Curitiba

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Vianna AGD, de Lacerda CS, Pechmann LM, Polesel MG, Marino EC, Borba VZC, Barreto FC. Vildagliptin has the same safety profile as a sulfonylurea on bone metabolism and bone mineral density in post-menopausal women with type 2 diabetes: a randomized controlled trial. Diabetol Metab Syndr. 2017 May 15;9:35. doi: 10.1186/s13098-017-0232-2. eCollection 2017.

• Responsible Party: Centro de Diabetes Curitiba Ltda
• ClinicalTrials.gov Identifier: NCT01679899
• Other Study ID Numbers: BoneGlyc
• First Posted: September 6, 2012
• Last Update Posted: November 4, 2016
• Last Verified: November 2016

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Centro de Diabetes Curitiba Ltda:

diabetes; type 2 diabetes mellitus; osteopenia; osteoporosis; glycemic variability; bone markers; osteocalcin; NTX; CTX; BALP

Additional relevant MeSH terms:

Osteoporosis; Bone Diseases, Metabolic; Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Bone Diseases; Musculoskeletal Diseases; Vildagliptin; Gliclazide; Hypoglycemic Agents; Physiological Effects of Drugs; Dipeptidyl-Peptidase IV Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action